Mineral Trioxide Aggregate/Ferric Sulfate Pulpotomy for Vital ...
169
Mineral Trioxide Aggregate/Ferric Sulfate Pulpotomy for Vital Primary Incisors: A Randomized Controlled Trial By Trang Doan Nguyen A thesis submitted in conformity with the requirements for the degree Master of Science Graduate Department of Pediatric Dentistry University of Toronto © Copyright by Trang Doan Nguyen (2014)
Transcript of Mineral Trioxide Aggregate/Ferric Sulfate Pulpotomy for Vital ...
Mineral Trioxide Aggregate/Ferric Sulfate Pulpotomy for Vital Primary Incisors: A Randomized Controlled Trial
By
Trang Doan Nguyen
A thesis submitted in conformity with the requirements for the degree Master of Science Graduate Department of Pediatric Dentistry
University of Toronto
© Copyright by Trang Doan Nguyen (2014)
! ii!
Mineral Trioxide Aggregate Pulpotomy for Vital Primary Incisors: A Randomized Controlled Trial Master of Science (Pediatric Dentistry) Year of Convocation: 2014 Trang Nguyen
Purpose: To compare clinical and radiographic outcomes and survival of mineral
trioxide aggregate/ferric sulfate (MTA/FS) pulpotomy and root canal therapy (RCT) in
carious vital primary maxillary incisors.
Methods: Asymptomatic carious vital primary incisors with pulp exposure in healthy
children aged 18 to 46 months were allocated randomly to receive MTA/FS pulpotomy or
RCT. Clinical and radiographic post-treatment assessments occurred at 6-month
intervals for up to 40 months. Two disinterested raters classified each incisor into one of
the following radiographic outcomes: N=incisor without pathologic change;
Po=pathologic change present, follow-up recommended; Px=pathologic change present,
extract.
Results: Eighteen-month outcomes demonstrated no statistical difference in clinical or
radiographic outcomes for MTA/FS pulpotomy and RCT incisors (P>.05). Survival
analysis demonstrated no statistically significant difference in survival for MTA/FS
pulpotomy and RCT incisors (P>.05) over a 6 to 40 month follow-up interval.
Conclusions: MTA/FS pulpotomy is an effective treatment for carious vital primary
incisors.
!
! iii!
Acknowledgements
I would like to thank Drs. Peter Judd and Michael Casas for their guidance, support and dedication throughout the entirety of this thesis project. I have learnt so much and I am grateful to you both. Thank you to Drs. Edward Barrett and Michael Sigal for their advice, recommendations and support. I would like to thank Drs. Sonia Chung and David Farkouh for rating radiographs and Drs. Randi Fratkin and Ihab Suwwan for providing clinical care to a portion of the study subjects. Appreciation is also extended to Derek Stephens for statistical support throughout the investigation. Thank you to the dental staff at The Hospital for Sick Children. A project of this magnitude would not have been possible without your contributions. Thanks to my fellow residents and in particular my classmates Basma, Darsi and Ed for a wonderful few years together. Finally, thank you to my friends and family for your unwavering support and encouragement throughout this process.
! iv!
Table&of&Contents&
Abstract(.......................................................................................................................................(ii!Acknowledgements(...............................................................................................................(iii!Abbreviations(..........................................................................................................................(vi!Chapter(1(9(Literature(review(..............................................................................................(1!1.(Introduction(...................................................................................................................................(1!2.(The(pulp9dentin(complex(...........................................................................................................(1!2.1.!Anatomy!and!histology!of!the!primary!dental!pulp!.................................................................!1!2.2.!Neurovascular!component!of!the!primary!dental!pulp!..........................................................!4!2.3.!Dentin!...........................................................................................................................................................!6!2.4.!Neurovascular!differences!between!primary!and!permanent!pulps!...............................!8!2.5.!Pain!perception!in!primary!and!permanent!teeth!....................................................................!9!2.6.!Summary!..................................................................................................................................................!10!
3.(Physiologic(root(resorption(and(exfoliation(of(primary(maxillary(incisors(..........(11!4.(Dental(caries(................................................................................................................................(11!4.1.!Effect!of!dental!caries!on!the!pulpGdentin!complex!...............................................................!12!4.2.!Pulp!inflammatory/immune!response!to!dental!caries!......................................................!14!4.3.!Pulp!histological!changes!in!response!to!dental!caries!.......................................................!15!4.4.!Dentin!sclerosis!and!formation!of!tertiary!dentin!in!response!to!dental!caries!.......!15!4.5.!Pulp!histology!in!symptomatic!and!asymptomatic!carious!teeth!...................................!17!4.6.!Summary!..................................................................................................................................................!17!
5.(Rationale(for(preservation(of(the(primary(dentition(....................................................(18!5.1.!Effect!of!dental!treatment!of!primary!teeth!on!normal!growth!and!development!.!18!5.2.!Effect!of!dental!treatment!of!primary!teeth!on!quality!of!life!...........................................!19!5.3.!Effect!of!premature!loss!of!primary!teeth!on!speech!...........................................................!20!5.4.!Summary!..................................................................................................................................................!20!
6.(Diagnosis(of(pulp(status(...........................................................................................................(20!6.1.!!Diagnosis!of!pulp!status:!accuracy!of!clinical!and!radiographic!findings!...................!22!6.2.!Diagnosis!of!pulp!status:!dental!history!.....................................................................................!23!6.3.!Diagnosis!of!pulp!status:!clinical!findings!.................................................................................!25!6.4.!Diagnosis!of!pulp!status:!radiographic!findings!.....................................................................!28!6.5!Diagnosis!of!pulp!status:!nonGstandard!tests!............................................................................!30!6.6.!Diagnosis!of!pulp!status:!concerns!...............................................................................................!32!6.7.!Summary!..................................................................................................................................................!32!
7.(Vital(pulp(therapy(......................................................................................................................(34!7.1.!Indirect!pulp!therapy!.........................................................................................................................!34!7.2.!Direct!pulp!capping!.............................................................................................................................!36!7.3.!Pulpotomy!...............................................................................................................................................!37!7.4.!Formocresol!pulpotomy!....................................................................................................................!37!7.5.!Glutaraldehyde!pulpotomy!..............................................................................................................!43!7.6.!Zinc!oxide!eugenol!pulpotomy!.......................................................................................................!44!7.7.!Ferric!sulfate!pulpotomy!..................................................................................................................!45!7.8.!Sodium!hypochlorite!pulpotomy!..................................................................................................!50!7.9.!Calcium!hydroxide!pulpotomy!.......................................................................................................!50!7.10.!Vital!root!canal!therapy!in!primary!teeth!...............................................................................!51!7.11.!Mineral!trioxide!aggregate!pulpotomy!....................................................................................!54!
(
! v!
8.(Outcome(assessment(of(vital(pulp(therapy(in(primary(teeth(......................................(69!8.1.!Concerns!regarding!outcome!assessment!in!pulp!therapy!................................................!73!8.2.!Survival!analysis!...................................................................................................................................!75!
9.(Pulp(therapy(in(primary(incisors(.........................................................................................(76!10.(Restoration(of(primary(incisors(.........................................................................................(82!11.(Summary(of(literature(review(............................................................................................(86!1.12.(References(..............................................................................................................................(88!1.13.(Tables(&(Figures(.................................................................................................................(109!1.14.(Appendix(...............................................................................................................................(118!
Chapter(2.(Manuscript(.......................................................................................................(126!Mineral!Trioxide!Aggregate/Ferric!Sulfate!Pulpotomy!for!Vital!Primary!Incisors:!.....!126!A!Randomized!Controlled!Trial!...........................................................................................................!126!
2.1.(Abstract(...................................................................................................................................(126!2.2.(Objectives(................................................................................................................................(127!2.3.(Introduction(...........................................................................................................................(128!2.4.(Methods(...................................................................................................................................(129!2.5.(Results(......................................................................................................................................(135!2.6.(Discussion(...............................................................................................................................(138!2.7.(Conclusion(..............................................................................................................................(140!2.8.(Acknowledgements(.............................................................................................................(140!2.9.(References(..............................................................................................................................(141!2.10.(Figures(&(Tables(.................................................................................................................(144!2.11.(Appendix(...............................................................................................................................(148!2.11.1.!Protocol!...........................................................................................................................................!148!2.11.2.!Research!consent!form!.............................................................................................................!155!2.11.3.!Procedural!data!collection!form!...........................................................................................!159!2.11.5.!Radiographic!data!collection!form!......................................................................................!161!2.11.6.!Ethics!approval!............................................................................................................................!162!
!
!!
! vi!
Abbreviations
AAPD American Academy of Pediatric Dentistry
Ca(OH)2 calcium hydroxide
DPC direct pulp capping
ECC early childhood caries
EPT electric pulp test
FBS fetal bovine serum
FC formocresol
FS ferric sulfate
IPT indirect pulp therapy
IRM Interim Restorative Material
MTA mineral trioxide aggregate
NaOCL sodium hypochlorite
PC Portland cement
PBS phosphate buffered saline
PCO pulp canal obliteration
PDL periodontal ligament
ppm parts per million
QOL quality of life
RCT root canal therapy
ZOE zinc oxide eugenol
! vii!
!
! 1!
Chapter 1 - Literature review
1. Introduction
Dental caries is an infectious, transmissible, chronic disease that can lead to the
pathological destruction of dental hard and soft tissue. Dental caries can cause
inflammation and necrosis of the dental pulp. Pulpitis, left untreated, can lead to a
disruption in the normal growth and development of a child, pain, cellulitis, abscess and
systemic infection.1,2 Treatment for inflamed pulps includes pulp therapy or extraction.
The premature loss of primary maxillary incisors can adversely affect a child’s occlusion,
psychosocial development, articulation accuracy and facial esthetics.3-8 Pulp therapy
allows for the preservation of primary teeth with inflamed pulps in a quiescent state.
Currently, there is a paucity of dental literature with regards to pulp therapy in primary
incisors.
2. The pulp-dentin complex
Dentin and pulp are histologically distinct but are often considered a single functional
entity termed the pulp-dentin complex due to their similar embryological origin and
integrated function. The pulp produces dentin and provides nutrients and innervation to
the dentin while the dentin provides protection for the pulp.9
2.1. Anatomy and histology of the primary dental pulp
The primary dental pulp is a specialized soft tissue of mesenchymal origin that forms
during the sixth week in utero.9 Pulp tissue is primarily composed of connective tissue
! 2!
fibers, fibroblasts, odontoblasts, ground substance, interstitial fluid, Schwann/nerve cells,
endothelial cells, red blood cells, white blood cells and stem cells.9 The pulp occupies
the central portion of a tooth and is encased within mineralized dentin.
The morphology of the pulp tends to conform to the general anatomical shape of the
tooth. The root canal system includes the pulp chamber, which contains the coronal pulp,
and the root canal, which contains the radicular pulp. The pulp tissue terminates at the
apical foramen where the majority of nerves and vessels enter and leave the tooth. In a
developing tooth, the apical foramina are initially large but reduce in diameter as the
tooth matures through secondary dentinogenesis. Accessory and lateral canals, as well as
their foramina, may exist along the root surface providing a limited collateral source of
innervation and fluid exchange.
Maxillary primary incisors tend to have a single canal. The pulp chamber tends to be
oval and compressed labio-lingually when viewed in cross-section. Maxillary primary
incisors have a slight S-shape when viewed proximally with the cervical portion tending
to curve lingually while the apical half curves labially.10,11 Accessory and lateral canals
are rare. The labial surface of the maxillary central primary incisors may display a
longitudinal groove but root bifurcation is rare.11
Histologically, 4 distinct zones characterize the dental pulp.9 The zones are the
odontoblast layer, cell-free zone, cell-rich zone and pulp core. The first zone is the
odontoblast layer located at the periphery of the pulp chamber. This layer is comprised
! 3!
of a single layer of odontoblasts and their processes that extend into the dentin.
Odontoblasts are responsible for the synthesis and secretion of the predentin extracellular
matrix and dentin mineralization. Odontoblasts are present as a single layer of cells that
appear 3 to 5 cells thick due to variations in height and cell crowding that result in
staggering of the odontoblasts. Dentin, capillary networks, terminal axons of
unmyelinated nerve fibers, collagen fibrils, proteoglycans, dendritic cells and fibronectins
comprise the substance among odontoblasts and their processes.
Odontoblasts are post-mitotic terminally differentiated cells that cannot proliferate to
replace irreversibly injured odontoblasts. Stem cells are capable of differentiating into
odontoblast-like cells when primary odontoblasts are irreversibly injured in the dental
pulp.12 Stem cells comprise between 2 to 9 percent of cells in the dental pulp in primary
teeth.13,14 Odontoblast-like cells have a similar function and morphology to odontoblasts,
however the mechanisms by which odontoblast-like cells form or differentiate are
different from odontoblasts.12
The second zone is the cell-free zone, or also termed the cell-free zone of Weil, located
adjacent to the odontoblasts and predominantly in the coronal pulp. This zone is
comprised of a rich network of unmyelinated nerve fibers (Raschkow's plexus), blood
capillaries and fibroblast processes. This zone is responsible for providing nutrients to
the odontoblast and sensory innervation to the dentin.9
The third zone is the cell-rich zone where cellular density is highest among the 4 zones.
! 4!
This layer is comprised of fibroblasts, stem cells, macrophages, lymphocytes, capillaries
and nerve fibers.
The pulp core is the fourth zone and characterized by the major vessels and neural fibers
of the pulp. This zone is also comprised of fibroblasts, stem cells, macrophages and
collagen fibers. The zone characteristically shows an overall increase in cellular density
towards the root apex. This layer is histologically similar to the cell-rich zone but is
differentiated by a lower density of fibroblasts.9
2.2. Neurovascular component of the primary dental pulp
The neurovasculature regulates the interstitial environment, sensory conduction,
inflammatory responses and dentinogenesis within the pulp. The pulp vasculature
maintains homeostasis of pulp tissue through the transportation of nutrients, hormones
and gases and the removal of metabolic waste products.
The dental pulp vasculature is a microcirculatory system as it lacks true arteries and veins
with its largest vessels being arterioles and venules.15 The majority of blood vessels enter
and leave the pulp through the apical foramen. A smaller number of blood vessels enter
and exit through accessory foramina. As arterioles enter the apical foramen and extend
coronally, their lumen increases in size and the frequency of lateral branching increases.
These lateral branches further divide to form an extensive capillary network in the
coronal portion of the pulp.9 Arteriovenous anastomoses occur throughout the pulp
tissue. Arteriovenous shunts permit blood to flow directly from the arterial to the venous
! 5!
side of circulation bypassing the capillary network. The vascular system is composed of
extensive venules that traverse apically and exit through the apical foramen.9
The lymphatic system is a network of vessels that aid in local tissue homeostasis through
nutrient and fluid distribution and the recirculation of interstitial fluid into the
bloodstream. Lymph vessels in the pulp are found predominantly in the pulp horns and
to a lesser extent, throughout the root.16,17 Unlike the vascular components of the pulp
where capillaries are not able to absorb high molecular proteins, the lymphatic system is
able to remove high molecular weight solutes from pulp tissue thereby reducing
interstitial osmotic pressure.
Nerve fibers within the pulp-dentin complex are responsible for sensory conduction and
neurogenic modulation of microcirculation, inflammatory reactions and implicated in
dentinogenesis.18,19 Sensory nerve fibers within the pulp have their cell bodies situated in
the trigeminal ganglion and sympathetic fiber bodies are located in the cervical
sympathetic ganglia. The majority of nerve fibers enter the teeth through the apical
foramen as a component of the neurovascular bundle. As the neurovascular bundle
extends coronally, nerve fibers branch with increased frequency with the majority of
nerve endings terminating in the cell-free zone to form the subodontoblastic plexus of
Raschkow. A small number of nerve endings extend further into the dentinal tubules.
Six types of sensory neurons are present in the human dental pulp: A-beta, A-delta-fast,
A-delta-slow, nociceptive C, glial derived neurotrophic factor regulated C and polymodal
! 6!
nociceptive C fibers. Approximately 80 percent of sensory axons are unmyelinated. The
exact function of each individual type of nerve fiber is unclear but A-fibers and C-fibers
have functional overlap as both can induce a nociceptive response. The majority of these
sensory neurons, when stimulated, provoke a nociceptive response. However, some
demonstrate an efferent function through the release of neuropeptides and increase of
blood flow within the dental pulp 20-22
Sympathetic fibers of the pulp are less numerous than sensory fibers. They are located
deeper within the pulp and follow a similar distribution pattern to the vasculature of the
pulp.23 Activation of sympathetic nerve fibers tends to lead to the vasoconstriction of
adjacent blood vessels and a reduction in pulpal blood flow.24-25 Some sympathetic
neurons, however, release neuropeptides that stimulate vasodilation and increase blood
flow.26
2.3. Dentin
Dentin is porous mineralized tissue made up of collagen and apatite crystals. In utero,
epithelial cells in the inner and outer dental epithelium proliferate from the cervical loop
of the enamel organ to form Hertwig’s epithelial root sheath. The epithelial sheath grows
apically until it encloses the pulp.9 Immature teeth have larger apical foramina and
thinner dentin walls than mature teeth. As teeth mature and dentin is produced, root
canals narrow and the apical foramina decrease in diameter. Maxillary primary incisors
complete root formation and constriction of the apex at 18 to 24 months of age or
approximately 1 year after eruption into the oral cavity.27
! 7!
Odontoblasts secrete an organic matrix that forms primary, secondary and tertiary dentin.
Primary and secondary dentin, the majority of tooth hard structure, consists of organized
dentin tubules and odontoblastic processes (Figures 2 and 3). Primary dentin is formed
until root development is complete. Secondary dentin is circumpulpal dentin that
develops after root formation is complete. Tertiary dentin forms in response to noxious
stimuli such as caries, attrition, trauma, masticatory forces and restorative procedures.
Tertiary dentin is produced by odontoblasts and odontoblasts-like cells and can be
reactionary or reparative. Reactionary dentin is secreted by preexisting odontoblasts and
tends to be well organized and tubular. Reparative dentin is secreted by stem cells that
mature to become odontoblast-like cells. Stem cells from the pulp must be recruited and
induced to differentiate into odontoblast-like cells prior to the secretion of a dentin
matrix. Reparative dentin can show a broad spectrum of appearances ranging from
regular and tubular to dysplastic and atubular.18
Dentin contains fluid-filled tubules that facilitate the hydrodynamic stimulation of nerve
fibers in dentin and pulp tissue. Dentinal tubules are continuous with the pulp and allow
for fluid exchange between dentin and pulp tissue.28 An increase in dentinal tubule fluid
flow stimulates an increase in fluid and protein flow out of the pulp into dentin.29 The
outward fluid flow is postulated to have a protective flushing action that reduces the
diffusion of noxious substances into the pulp. Dentinal tubules may undergo sclerosis in
response to various stimuli including caries, attrition, abrasion and erosion. Dentin
sclerosis occurs when the dentinal tubules become partially or completely filled with
hydroxyapatite and whitlockite crystals.18 Dentin sclerosis reduces the permeability of
! 8!
dentin by obstructing tubules and thereby reducing irritation to the pulp.30
2.4. Neurovascular differences between primary and permanent pulps
In general, the anatomy and histology of primary and permanent dental pulps are similar.
Primary and permanent tooth pulp horns show significantly greater neural density than all
other regions of the coronal pulp.31 The innervation of blood vessels and distribution of
neurons along blood vessels are also similar in both dentitions.32 However, permanent
teeth have a greater density of neurons in all regions of the pulp than primary teeth.31,33,34
Despite the difference in neural density between primary and permanent teeth, no clinical
differences in sensory or somatic responses have been demonstrated between primary and
permanent teeth.
The number and distribution of blood vessels in the pulp horn and subodontoblastic
regions of primary and permanent molar pulps are similar.35 However, primary molars
demonstrate a greater number of vessels in the mid-coronal region of the pulp than
permanent molars. The difference in vascularity is speculated to reflect increase
functional demands of the physiological resorption process or wider apical foramina that
facilitate more blood vessels to enter the pulp of primary compared to permanent teeth.35
The leukocyte density in the pulp horn and mid-coronal regions of the pulp is greater in
primary than permanent teeth.36 The greater number of leukocytes in the primary than
permanent tooth pulps is speculated to be related to the physiological resorption process
in primary teeth or a greater immune response in primary teeth than permanent teeth
! 9!
secondary to more porous enamel and dentin that is less resistant to antigenic
substances.36
2.5. Pain perception in primary and permanent teeth
Clinicians report anecdotally that primary teeth are less sensitive to noxious stimulation
than permanent teeth, however there is currently no high quality evidence to support this
assertion.33,37 Though primary teeth contain fewer neurons and myelinated neural fibers
than permanent teeth, the overall anatomy and distribution of neural tissue within primary
and permanent pulps are similar.31-33,35,36 Pulp sensibility testing demonstrates primary
and permanent teeth respond similarly to noxious stimuli.38,39 Although neural density is
greater in permanent teeth than primary teeth, investigators have not been able to
differentiate between specific nerve populations in the pulp. The greater neural density in
permanent than primary teeth may not correlate with an increase in sensory neural fibers
that are responsive to noxious stimuli.31
An immature autonomic system in infants and children is speculated to be the cause of
nociceptive responses reported less frequently in the primary dentition than permanent
dentition. However, there is evidence that nocioceptive receptors, though still immature,
are functional in the fetus.40 Reflex movements often characterize noxious responses.
Examples of reflex movements include withdrawal reflexes, increases in heart rate and
facial movements. Muted reflex responses to noxious stimuli in infants might be related
to immature sympathetic responses in children and not their ability to perceive pain.41,42
! 10!
Children may report less pain in decayed teeth due to their cognitive development. For a
child to designate the intensity of a pain experience, the child must be able to rank the
severity of their pain. Approximately 40 percent of 5- and 6-year-old children
experienced difficulty using pain scales because they are not able to rank their pain.43
Children who acquire caries at an early age may have limited experience being free of
dental pain and therefore may not be able to easily differentiate between painful and pain-
free states.
2.6. Summary
The pulp and dentin are considered a single functional entity due to their integrated
function and similar embryological origin. Dentin is a mineralized tissue that surrounds
the pulp and protects the pulp from injury. Dentinal tubules are continuous with the pulp
and allow for fluid exchange between dentin and pulp tissue. The majority of neural
fibers and blood vessels enter and exit the pulp through the apical foramen. A smaller
number of blood vessels enter and exit through accessory foramina.
The pulp-dentin complex is comprised of an extensive neural, vascular and lymphatic
system that is involved in tissue homeostasis through the transportation of nutrients,
hormones and gases and through the removal of metabolic waste products. Primary pulps
demonstrate fewer nerve fibers and greater vascular density than permanent pulps. Minor
differences exist between the dental pulps of primary and permanent teeth but overall the
function and structure of permanent and primary pulps are similar.
! 11!
3. Physiologic root resorption and exfoliation of primary maxillary incisors
Physiological root resorption is a normal process that leads to the exfoliation of primary
teeth. There is a paucity of literature regarding the initiation of physiological root
resorption of primary maxillary incisors however, there is evidence documenting the
development and eruption of permanent maxillary incisors. 44 Physiological root
resorption typically starts at approximately 5 to 7 years of age but can begin as early as 4
years of age in primary maxillary incisors based on extrapolated data from permanent
tooth development.44 Primary maxillary incisors exfoliate and are replaced by permanent
maxillary incisors between the ages of 7 and 9 years of age. Normal tooth exfoliation
may be disrupted by periapical/periradicular pathosis and pulp therapy.45
4. Dental caries
Dental caries is an infectious, transmissible, chronic disease that can lead to the
pathological destruction of dental hard and soft tissue. Caries has a multifactorial
etiology that involves a carbohydrate substrate, susceptible tooth surface as well as
acidogenic (acid-producing) and aciduric (acid-tolerating) bacteria.46
Dental plaque is a biofilm that forms on tooth surfaces where microorganisms and dietary
carbohydrates concentrate. Dental plaque associated with sound tooth structure consists
predominantly of non-acidogenic and non-aciduric bacteria from which acid production
is minimal. Acidogenic bacteria in dental plaque produce acids as a by-product of
carbohydrate metabolism. Under prolonged acidic conditions, aciduric bacteria become
dominant through selective adaptation. Acid production subsequently leads to a decrease
! 12!
in environmental pH. The critical pH threshold at which dissolution of enamel
commences is pH 5.5.9 A persistently low environmental pH promotes demineralization
of tooth surfaces that can progress to the destruction of hard and soft tooth structure.
Dental caries is the most common chronic bacterial infectious disease in children. Dental
caries is 5 times more common than asthma and 7 times more common than hay fever in
children.47 Caries risk considerations unique to infants and young children include
timing of cariogenic bacteria acquisition, ad libitum infant/early childhood feeding
practices and establishment of childhood feeding preferences. Inappropriate dietary
practices (e.g. non-nutritive feedings) and lack of oral hygiene put the primary dentition
at risk for decay soon after eruption. The maxillary incisors are at particular risk due to
prolonged exposure to fermentable carbohydrates during suckling primarily during sleep.
Mandibular incisors are not equally affected as maxillary incisors as the tongue covers
mandibular incisors during suckling protecting them somewhat from carbohydrate
exposure.
4.1. Effect of dental caries on the pulp-dentin complex
Caries is the most common cause of pulpal inflammation. Cariogenic bacteria can induce
pulpal inflammation through direct contact or contact of their byproducts with the pulp-
dentin complex. The immune system is often unable to access and eliminate pathogenic
microorganisms affecting enamel, dentin and cementum because of the avascular nature
of these tissues. Unlike infections in other parts of the body, caries often requires local
intervention, as systemic therapies are not effective treatment against caries.
! 13!
The pulp is a microcirculatory system encased in dentin that resists volume changes
within the pulp. These properties of the pulp-dentin complex gave rise to the pulp self-
strangulation theory. The theory suggests that with the limited volume exchange and the
rigid encased environment of the pulp, edema secondary to inflammation decreases blood
flow which then causes an increase in interstitial pressure to the point that exceeds pulp
vascular pressure. Subsequently, vascular collapse and pressure necrosis of the pulp may
occur through cessation of blood flow. However, there is weak evidence to support the
theory of pulp strangulation as increases in pulpal interstitial pressure from inflammation
have been demonstrated to not result in vascular collapse and necrosis.48,49 Increases in
pulp interstitial pressure at the site of inflammation are caused by increases in blood
vessel permeability and plasma exudation as well as vasodilation of blood vessels.50
However, the pulp opposes increases in interstitial pressure by increasing lymphatic
drainage, capillary filtration, blood flow, dentinal fluid movement and angiogenesis.51
As long as physiological feedback mechanisms that counteract increases in interstitial
pressure remain functional, the pulp has the ability to restrict pulp inflammation to the
site of injury.51
The natural course of pulpitis is not well understood. The inflammatory response is a
complex series of events under the influence of multiple regulatory systems including the
paracrine, autocrine and endocrine systems. A transient inflammatory response is useful
in clearing foreign antigens and producing an environment conducive to regeneration and
healing. However, severely damaged pulp tissue may not be capable of healing and may
progress to necrosis. With the accumulation of areas of local tissue necrosis, eventual
! 14!
complete necrosis of the pulp may occur.
4.2. Pulp inflammatory/immune response to dental caries
Inflammation is a complex mechanism initiated in response to harmful stimuli and can be
classified as either acute or chronic.52 Acute inflammation is the immediate response of a
host to harmful stimuli and characterized by vasodilation, increased vascular permeability
and recruitment of leukocytes.53,54 Leukocytes remove pathogens via the vascular and
lymphatic systems .55,56 The duration of acute inflammation can last minutes to days.
Outcomes of acute inflammation include tissue healing with or without fibrosis or
progression to chronic inflammation. Acute inflammation progresses to chronic
inflammation in cases of persistent injury or infection, prolonged exposure to toxic agents
or autoimmune diseases.
Chronic inflammation is a low-grade inflammatory response that aims to remove or
contain harmful stimuli while mediating the destruction of inflamed and necrotic tissue in
order to promote new tissue growth. Chronic inflammation can last for days to years.
The transition from acute to chronic is gradual and marked by a change in cellular
components, tissue destruction and repair of injured tissue. Chronic inflammation is
characterized by the accumulation of lymphocytes, plasma cells and macrophages,
angiogenesis and lymphangiogenesis. Angiogenesis and lymphangiogenesis enhance
transport of fluid, proteins and immune cells to meet increased demands for fluid
movement.57 Dentin sclerosis and production of tertiary dentin are unique features seen
only in chronic inflammation of the pulp-dentin complex.58 Dentin sclerosis reduces the
! 15!
permeability of the pulp-dentin complex and tertiary dentin forms an additional barrier
against bacteria and their toxins.59
4.3. Pulp histological changes in response to dental caries
In general, pulpal inflammation increases as carious lesions increase in size or progresses
towards the pulp. 36,60-63 The presence, absence and quality of tertiary dentin varies
among carious lesions and correlates with the nature of the caries progression.62,64 In
slowly progressing lesions, tertiary dentin is more often reactionary. In rapidly
progressing lesions, reparative dentinogenesis is more often reported as the death of
primary odontoblasts is more likely to occur than in slowly progressing carious lesions.65
In teeth with rapidly progressing dentin lesions, tertiary dentin tends to be atubular or less
tubular and less calcified than teeth with slowly progressing dentin lesions.
Caries is a dynamic process and may alternate between periods of rapid and slow
progression. Carious lesions can also present with multiple caries progression rates
within a single lesion.64 As a consequence, pulp histopathology may be representative of
a blend of multiple caries progression rates.
4.4. Dentin sclerosis and formation of tertiary dentin in response to dental caries
The formation of tertiary and sclerotic dentin in carious teeth is proposed to be a
protective mechanism against the ingress of pathogenic bacteria and their byproducts.
Dentin tubules are a path by which bacteria and their toxins may gain access to the pulp.
Sclerotic dentin reduces the permeability of the dentin to bacteria. Bacteria progresses
! 16!
through dentinal tubules more slowly in vital than necrotic dentin.66 The difference in the
rates of bacterial ingress between vital and necrotic dentin is speculated to be due to the
fluid flow from the pulp toward the dentin-enamel junction and immunoglobulins present
in vital dentin. Formation of tertiary dentin and dentin sclerosis indicates that the dental
pulp is vital and has the potential for pulpal regeneration and repair.
Tertiary dentin is speculated to act as a barrier between the pulp and pathogenic bacteria
and their byproducts. An association between tertiary dentin formation and resolution of
pulpal inflammation has been demonstrated.55 In rats, caries-induced pulpitis was
reported to subside after tertiary dentin formation occurred at the pulp-dentin interface.55
However, pulpal inflammation was again reported once caries progress into tertiary
dentin. The effectiveness of tertiary dentin as a barrier against pathogenic bacteria may
be dependent on the structure of tertiary dentin, which can be variable. Tertiary dentin
tends to be more irregular, less mineralized, have more cellular inclusions and contains
fewer dentinal tubules than primary and secondary dentin. Mild injuries tend to form
tertiary dentin that is more regular and mineralized resembling primary and secondary
dentin while more severe injuries are associated with more irregular and less mineralized
dentin. The dentinal tubules between secondary and tertiary dentin are often
discontinuous.
Tertiary dentin can form at the site of pulp exposure where a pulp-capping medicament
has been placed over the pulp exposure and the tooth is sealed with a liner and/or
restoration. Tertiary dentin that forms at the site of pulp exposure is often termed a
! 17!
dentin bridge. Many dentin bridges contain remnants of pulp tissue, operative debris and
structural defects that present where the pulp is in contact with the pulp-capping
medicament. Though formation of a dentin bridge is postulated to be protective against
bacterial invasion, it is unclear if a dentin bridge provides an effective barrier against
bacteria and bacterial toxins.
4.5. Pulp histology in symptomatic and asymptomatic carious teeth
Pain is a subjective sensation involving multiple physiological processes including
sensory, emotional, conceptual and behavioral aspects.67 Pain history in children with
grossly carious primary teeth is not correlated with the degree of pulpal inflammation or
density of vasculature or neural density within the pulp.36,72,68
4.6. Summary
Dental caries is an infectious chronic disease and the most common cause of pulpal
inflammation. The pulp-dentin complex is capable of undergoing dynamic tissue
changes in response to caries including increases in fluid circulation and permeability,
infiltration of leukocytes, angiogenesis, dentin sclerosis and tertiary dentin formation in
order to maintain tissue homoeostasis. The rate of caries progression is often reflected by
the quality of tertiary dentin and degree of dentin sclerosis. Slowly progressing lesions
tend to have tertiary dentin resembling normal tubular dentin while rapidly progressing
lesions are associated with atubular dentin or the absence of tertiary dentin. As caries
progresses, the severity of inflammation within the pulp increases and pulp necrosis and
infection can be the consequence. Pain history in primary teeth is not correlated with the
! 18!
degree of pulpal inflammation or density of innervation within the pulp.
5. Rationale for preservation of the primary dentition
A healthy primary dentition can be important for normal growth and development. The
premature loss of primary maxillary incisors can adversely affect a child’s occlusion,
psychosocial development, articulation accuracy and facial esthetics.1-8,69
Primary teeth aid in the mastication of food with variations in tooth shape that reflect
different functional roles. Incisors are chisel or wedged shaped teeth that are used in
parcelling food. Canines are used to tear and rip food and primary molars are used to
grind and chew food.
5.1. Effect of dental treatment of primary teeth on normal growth and development
Oral health can be an integral part of overall general health.1,5,69 Children with early
childhood caries (ECC) are more likely to suffer from malnutrition and failure to thrive
than children who are caries-free.1,69 Fourteen percent of children with ECC weighed
less than 80 percent of their ideal weight, satisfying a criterion for the designation of
failure to thrive.1 Twenty-five percent of children with severe ECC exhibited evidence of
malnutrition by anthropometry.69 Blood tests were more effective than anthropometry for
detection of nutritional deficiency. Blood tests results demonstrated evidence of
inadequate iron intake with low serum ferritin in 80 percent, iron depletion in 24 percent,
iron deficiency in 6 percent and iron deficiency anemia in 11 percent of children with
ECC. Chronic iron deficiency is associated with impaired physical growth, brain
! 19!
development and behavioral development and decreased activity level.
There is low-level evidence to support that children with ECC exhibited normal growth
and development after dental rehabilitation.1 Children with ECC who underwent
comprehensive dental treatment under general anesthesia exhibited significant catch up
growth post-dental treatment.1 After approximately 1.5 years after dental rehabilitation,
the weight of children with ECC who underwent dental rehabilitation was not different
from caries-free children.
5.2. Effect of dental treatment of primary teeth on quality of life
Children with ECC have a lower quality of life (QOL) than children who are caries-free.5
Parents of children affected by ECC perceive their children to have greater pain, poorer
oral function and more psychological issues related to their oral health compared to
children free of caries.5 However, after dental rehabilitation, children with ECC
demonstrate significantly improved QOL 4-weeks post-dental rehabilitation.
Parents, regardless of socioeconomic status, all agree grossly carious teeth and carious
teeth with visible sinus tracts are unhealthy and unattractive.6 Children without caries
show more teeth when smiling and evaluate their own smiles more positively than
children with ECC. Parents also evaluate the smiles of caries-free children more
positively than children with ECC.70 Dental features are reported to be the fourth most
common cause for teasing between the ages of 9 and 13 after height, weight and hair.3
! 20!
5.3. Effect of premature loss of primary teeth on speech
Conflicting low-level evidence exists to whether children with premature loss of their
primary maxillary incisors demonstrate more articulation errors than children with intact
dentitions.4,71 However, no children with premature loss of their primary maxillary
incisors demonstrate speech articulation errors that persist into adolescence and
adulthood.4
5.4. Summary
Untreated dental caries in the primary dentition is associated with malnutrition and failure
to thrive. Caries-free children or children who have undergone dental rehabilitation
demonstrate higher QOL than children with ECC. Parents of children affected by ECC
perceive their children to have greater pain, poorer oral function and more psychological
issues related to their oral health compared to children free of caries. Though children
with premature loss of primary incisors may demonstrate more speech articulation errors
than children with intact dentitions, speech articulation errors do not persist into
adolescence and adulthood.
6. Diagnosis of pulp status
The status of the pulp determines the treatment choice in pulp therapy. Vital pulp therapy
is reserved for teeth with pulps that maintain their reparative and healing potential. Non-
vital pulp therapy is utilized in teeth with pulps that have lost their reparative and healing
potential. Non-vital pulp therapy is indicated in necrotic pulps or vital pulps injured
beyond repair. Vital pulps injured beyond repair will eventually progress to necrosis if
! 21!
left untreated.
Various terminology and classification systems to describe pulpal status have been
developed by clinicians over the years. In 2008, the American Association of
Endodontists convened a consensus conference on diagnostic terminology in an attempt
to standardize the terminology used for the classification of pulp status.72 Pulp status is
categorized into four classifications: normal pulp, reversible pulpitis, irreversible pulpitis
and necrotic pulp. Reversible pulpitis is where the pulp is inflamed but the pulp
maintains its reparative and healing potential. Irreversible pulpitis is where the pulp is
inflamed and the pulp does not have reparative or healing potential. Necrotic pulps can
function as a substrate for bacterial growth and lead to localized or systemic infections.72
A limitation of this classification system is that the diagnosis of pulp status is subjective
and may not be representative of the actual histological state of the pulp. Objective
assessment of pulp status would require the removal and histological examination of
affected tissue, which is not practical in a clinical setting. Thus, the accurate clinical
diagnosis of pulp status may not correspond with the exact histologic condition of the
pulp. To cope with this diagnostic dilemma, clinicians and investigators differentiate
between pulp status categories on an empirical basis using clinical and radiographic signs
correlated with histological signs of pulpal inflammation and infection.
An association between the degree of pulpal inflammation and outcome of vital pulp
therapy has been demonstrated in primary molars.73 The degree of inflammation in the
! 22!
pulp was measured using an inflammatory mediator (prostaglandin E2) prior to vital pulp
therapy. Higher prostaglandin E2 counts correlated positively with unacceptable
outcomes of vital pulp therapy.
Clinicians rely on clinical and radiographic interpretation using accepted signs and
symptoms that indicate the severity of pulpal inflammation. However, the degree of pulp
inflammation that delineates reversible pulpitis from irreversible pulpitis is currently
unknown. Clinicians consider inflammation of radicular pulp tissue as irreversible
pulpitis despite no evidence to support that this is an accurate measure of the pulps
healing capacity. Pulps free of radicular pulpal inflammation contain healthy pulp tissue
with the capacity to heal and candidates for vital pulp therapy.
Clinicians assess multiple clinical signs and symptoms and radiographic signs to
determine pulp status. Clinical signs and symptoms that clinicians often use to assess
pulp status include pain, tooth percussion sensitivity, tooth mobility and/or presence of
swelling, sinus tract/fistulae. Radiographic diagnostic signs clinicians tend to use when
determining pulp status include presence of widened periodontal ligament (PDL),
periapical or furcation radiolucency, external or internal root resorption and/or pulp canal
obliteration (PCO).
6.1. Diagnosis of pulp status: accuracy of clinical and radiographic findings
Clinicians are able to correctly predict which primary teeth do not have radicular pulpal
inflammation and are candidates for vital pulp therapy based on clinical and radiographic
! 23!
findings in the majority of cases (81 to 92 percent).60,74 A small proportion of primary
teeth (8 to 19 percent) considered candidates for vital pulp therapy present with
undiagnosed radicular pulp inflammation that may affect treatment outcomes. Clinicians
are also able to predict primary teeth that were not candidates for vital pulp therapy based
on clinical and radiographic findings in 82 percent of cases.60
Koch and Nyborg correlated clinical and radiographic findings with histological pulpal
inflammation in 48 carious primary molars.60 Of the 26 primary molars judged to be
candidates for vital pulp therapy based on clinical and radiographic findings, 92 percent
of molars demonstrated inflammation confined to the coronal pulp. Of the 22 molars for
which vital pulp therapy was contradicted, 82 percent demonstrated inflammation of the
radicular pulp. In a similar study, Schroder demonstrated that of 37 primary molars
considered candidates for vital pulp therapy based on clinical and radiographic findings,
81 percent demonstrated inflammation confined to the coronal pulp while 19 percent of
teeth demonstrated radicular pulp inflammation. Kassa et al. demonstrated, in the
absence of clinical or radiographic evidence of irreversible pulpitis or pulp necrosis, only
1 of 78 carious primary molars presented with histological widespread inflammatory
changes extending into the radicular pulp.75
6.2. Diagnosis of pulp status: dental history
Clinicians routinely use pain history as an indicator of pulp status. Clinicians tend to
consider symptoms of severe, persistent, nocturnal or spontaneous pain as indicators of
irreversible pulpitis or pulp necrosis while symptoms of mild to moderate or intermittent
! 24!
pain as indicators of reversible pulpitis. Despite the routine use of pain history in primary
teeth as an indicator of pulpal inflammation, there is conflicting and no strong evidence
to associate pain history with pulpal inflammation.
In grossly carious primary molars, pain histories from children and their guardians were
not reliable predictors of pulpal inflammation.31 Grossly carious primary molars with a
positive pain history were not associated with differences in pulp innervation, vasculature
or leukocyte cell infiltration when compared to grossly carious molars with a negative
pain history.
In another investigation, children with a history of persistent pain had significantly more
radicular pulp inflammation than children with a dental history of intermittent pain.60
Children that presented with persistent pain in carious molars upon histological
examination demonstrated radicular pulp inflammation in 64 percent (16 of 25) of molars
while children that presented with intermittent molar pain demonstrated radicular
inflammation in only 17 percent (4 of 23) of molars.60
Despite existing evidence that pain history does not always demonstrate good correlation
to the histopathological condition of the pulp, clinicians still routinely use pain history to
aid in determining pulp status. This discrepancy may be related to the complex nature of
pain and diagnosis of pulp status and not that an association does not exist.
! 25!
6.3. Diagnosis of pulp status: clinical findings
Some clinical findings have been correlated to histological pulpal inflammation in
carious primary molars. Molars that presented with clinical signs and/or symptoms of
pain, sinus tract/fistula, swelling, pathological tooth mobility and/or pulp exposure were
assessed histologically.76 Of 53 molars assessed, 92 percent demonstrated inflammation
or necrosis of the coronal pulp and 76 percent of molars demonstrated inflammation or
necrosis of the radicular pulp.
Clinicians routinely consider the presence of swelling, fistulae/sinus tracts, tenderness to
tooth percussion and/or pathological tooth mobility as contraindications of vital pulp
therapy. Swellings, fistulae or sinus tracts associated with carious primary teeth
demonstrate a strong correlation to pulp necrosis and periapical pathoses.77 Investigators
often consider tenderness to tooth percussion or tooth mobility contraindications of vital
pulp therapy despite any strong evidence that these measures are strongly correlated with
pulpal inflammation or infection.60.78 A strong correlation between the histopathological
condition and tenderness to tooth percussion or tooth mobility has not been demonstrated
may be because of the multiple pathological processes that can cause tenderness to tooth
percussion or tooth mobility. Causes of these clinical findings can include pulpitis,
infection, trauma, periodontal disease or normal physiological processes.
Carious pulp exposures in primary molars are associated with pulpal inflammation.78
Eighty-four percent of 44 primary molars with carious pulp exposures had inflammation
that was confined to the coronal pulp, while 16 percent of molars demonstrated
! 26!
inflammation of the radicular pulp.78 Of 35 molars without clinical pulp exposure, 94
percent demonstrated inflammation confined to the coronal pulp. Carious pulp exposure
in primary incisors, unlike primary molars, demonstrated more variability in the degree of
pulpal inflammation. Of 24 incisors with pulp exposures, histological examination
revealed normal pulps in one-third, reversible pulpitis in one-third and irreversible
pulpitis/necrosis in one-third of incisors. Of 29 incisors without clinical pulp exposure,
69 percent demonstrated normal pulps, 10 percent demonstrated reversible pulpitis and
21 percent demonstrated irreversible pulpitis/necrosis. The difference in the degree of
pulpal inflammation between pulps with and without exposure were statistically
significant.79 Carious pulp exposures are strongly correlated with pulp inflammation,
however not the extent of pulpal inflammation. A better indicator of the extent of pulpal
inflammation might be to compare the extent or size of the carious pulp exposure to
pulpal inflammation and not simply the presence or absence of a pulp exposure. Primary
incisors with carious pulp exposure appear to demonstrate a greater variability in
histopathological conditions than molars with carious pulp exposures. The histological
variability of incisors may be a perceived rather than an actual difference as the
investigation did not take into consideration size of the pulp exposures. In addition, the
investigation did not account for the lack of anatomical distinction between the coronal
and radicular pulp tissue of incisors.
Large carious lesions (>1mm in diameter) are associated with greater pulp inflammation
when compared to small carious lesions (<1mm) in diameter.60 Radicular pulpal
inflammation was present in 74 percent (17 of 23) of molars with large sized carious
! 27!
lesions and only 12 percent (3 of 25) of molars with small sized carious lesions. Primary
molars with proximal caries demonstrate greater extent and severity of pulpal
inflammation than primary molars with caries confined to the occlusal surface when
caries depth are equal to, or greater than, 50 percent of the total dentin thickness.75
Primary molars with proximal caries and clinically visible marginal ridge breakdown are
associated with significantly more extensive coronal pulp inflammation than carious
lesions without marginal ridge breakdown.78,80 Of molars with caries affecting less than
two-thirds of the marginal ridge width, 90 percent of molars demonstrated coronal pulp
inflammation while 100 percent of molars with caries affecting greater than two-thirds of
the marginal ridge width demonstrated coronal pulp inflammation.
Direct evaluation of pulp tissue can aid in determining a clinical diagnosis of pulp status.
Dark (deep red or purple) colored or excessive bleeding from an exposed or amputated
pulp is associated with extensive pulpal inflammation in the primary dentition.60,74
Primary molars that presented with dark red or purple bleeding demonstrated
significantly more pulpal inflammation than molars that presented with light red colored
bleeding. Primary molars that presented with dark red or purple bleeding demonstrated
radicular inflammation in 71 percent (15 of 21) of molars while molars that presented
with light red bleeding upon coronal pulp amputation demonstrated radicular
inflammation in 16 percent (4 of 25) of molars.60 In the same study, molars that were
judged to have excessive hemorrhage upon coronal pulp amputation demonstrated
significantly more pulpal inflammation than molars that presented with minimal
hemorrhage upon coronal pulp amputation. Of 13 molars that presented with excessive
! 28!
hemorrhage, radicular inflammation was demonstrated in 77 percent of molars. Of 19
molars that presented with minimal hemorrhage, 11 percent demonstrated radicular
inflammation. Dark (deep red or purple) colored or excessive bleeding from an exposed
or amputated pulp demonstrates a strong correlation with pulpal inflammation.
Prolonged bleeding time following coronal pulp amputation has been considered a sign of
radicular pulp inflammation that contraindicates vital pulp therapy. Waterhouse et al.
assessed treatment outcomes of vital pulpotomy measured against mean bleeding time
following coronal pulp amputation. Bleeding times associated with acceptable clinical
and radiographic outcomes compared to bleeding times of those teeth with unacceptable
outcomes demonstrated no statistical significant difference. Mean bleeding time in
molars with acceptable post-operative clinical and/or radiographic outcomes (n=64) was
6.4 minutes compared with 6.9 minutes for teeth with unacceptable treatment outcomes
(n=15). Pulp bleeding time is an unreliable predictor of pulp therapy outcome.
6.4. Diagnosis of pulp status: radiographic findings
Common radiographic signs cited as contraindications to vital pulp therapy in primary
teeth include furcation or periapical radiolucencies, external root resorption, internal root
resorption or widened PDL as these signs are associated with pulpal inflammation and/or
pulp necrosis. Teeth with any of these radiographic features are not appropriate
candidates for vital pulp therapy.
Radiographic images of primary teeth that demonstrate furcation and periapical
! 29!
radiolucencies are associated with necrotic pulps where an abscess, a granuloma or a cyst
has developed secondary to an odontogenic infection.77 Furcation radiolucencies occur
predominantly in primary molars rather than permanent molars because of the porous
pulp floor and the presence of numerous accessory canals in the floor of the pulp
chamber. Apical radiolucencies are predominantly observed in permanent teeth and
primary incisors and canines. External root resorption on radiographic imaging is
indicative of pulp necrosis or extensive pulpal inflammation that has spread to adjacent
periapical tissues. The appearance of internal root resorption on radiographs is most
commonly associated with pulpal inflammation in vital pulps.81 Though some internal
resorption has been shown to arrest or reverse, internal root resorption may represent
widespread inflammation that may affect treatment outcomes.18
A widened PDL on radiographic exam may be representative of an inflamed or infected
PDL secondary to an inflamed or necrotic pulp. In irreversible pulpitis, inflammation of
the pulp may involve the entire length of the root(s) and extend into the PDL. Widened
PDL on radiographic exam has been demonstrated to be associated with pulpal
inflammation.60 Carious primary molars that presented with the radiographic appearance
of a widened PDL demonstrated radicular inflammatory cell infiltration in 86 percent of
molars while molars that presented with a radiographic appearance of a normal PDL only
demonstrated radicular inflammation in 33 percent of molars.60
PCO or calcific metamorphosis on radiographic images results from the formation of
tertiary dentin in the root canal produced by the chronic stimulation of odontoblasts and
! 30!
odontoblasts-like cells. The severity of PCO depends on the degree and duration of the
stimulus. PCO can be a physiological process that does not necessitate treatment in the
absence of signs or symptoms of infection.82-86
6.5 Diagnosis of pulp status: non-standard tests
Non-standard diagnostic tests in primary teeth include response to sensibility tests, laser
Doppler flowmetry, pulse oximetry and selective anesthesia. Pulp sensibility tests assess
pulp vitality through stimulation of pulpal sensory neurons and assessment of patient
response. Sensibility tests include: heat test, cold test, electric pulp test (EPT) and cavity
test. Thermal (hot and cold) and EPT are the most common tests used to assess pulp
vitality. These tests are affordable, easy to use and reliable in permanent teeth.39
Abnormal responses include prolonged sensations, immediate severe pain or absence of a
response. Petersson et al. compared the hot test, cold test and EPT efficacy for
identifying viable nerve tissue in permanent teeth. Hori et al. in a similar study compared
the hot test, cold test and EPT efficacy in identifying the presence of vital nerve tissue in
primary teeth. Pulpal status was determined by direct inspection of the pulp after access
cavity preparation to assess the presence or absence of bleeding. The results of
Peterrsson et al. and Hori et al. are summarized in Table 1.38,39 Sensitivity and specificity
results of hot test, cold test and EPT appear similar when identifying vital pulps in the
primary and permanent dentition.
There is limited evidence to support the standard use and cost versus benefit of sensibility
testing in the primary dentition. Clinicians have historically relied heavily on dental
! 31!
history, clinical findings and radiographic findings for diagnosis of pulp status in primary
teeth without standard use of sensibility testing. One reason is clinicians are already able
to predict pulp status, based on clinical and radiographic findings, with relative accuracy
(88 percent).60 The added benefit of sensibility testing may be minimal with the reported
sensitivities and specificities reported in Hori et al. The limited use of sensibility testing
in the primary dentition is also anecdotally attributed to unreliable responses, additional
time requirements, uncooperative behavior in children and/or concern that the tests may
provoke apprehension, fear and behavior management concerns. A limitation of
sensibility testing is it reflects the presence of conducting nociceptive fibers and not the
overall qualitative health of the pulp. Functioning pulpal sensory neural tissue is only
one aspect of pulpal health and does not take into account the health of the vasculature
and immune components of the pulp. Sensibility testing in primary teeth may be of value
when clinical and radiographic assessment is inconclusive.
Pulp vitality can be assessed with the cavity test using mechanical stimulation through
cavity preparation. Limitations of this test are loss of tooth structure and, like other
sensibility tests, the test does not assess overall pulpal health, only the presence of viable
nerve tissue. Laser Doppler flowmetry and pulse oximetry have been used to detect
pulpal blood flow. Both tests are not commonly used in clinical practice. Laser Doppler
flowmetry is showing promising results in regards to accurate and reliable assessments of
pulp status.87,88 Pulse oximetry, in contrast, is to date an unreliable test in the assessment
of pulp status.87
! 32!
6.6. Diagnosis of pulp status: concerns
Contraindications to vital pulp therapy include history of spontaneous or lingering
provoked pain, swelling, fistula/sinus tract, tenderness to percussion and pathological
mobility. Radiographic findings repeatedly considered contraindications to vital pulp
therapy include periapical or furcation radiolucency, widened PDL space, internal root
resorption or external root resorption. These classic signs and symptoms that
contraindicate vital pulp therapy may have to be reevaluated in the near future.
New research has demonstrated superior outcomes of calcium enriched-mixture
pulpotomy when compared to RCT in permanent teeth with irreversible pulpitis at 2-
years post-treatment.89 Though the results of this study have not been reproduced, the
results of the investigation raise the concern that may be the current diagnostic criteria
used demarcating reversible and irreversible pulpitis should be reevaluated. Measures
such as vascularity or pluripotent potential of stem cells might be better diagnostic
indicators of the reparative potential of pulp tissue and should be investigated in the
future.
6.7. Summary
The choice of vital pulp therapy technique and outcome of treatment is dependent on the
accurate diagnosis of pulp status. Primary teeth presenting with reversible pulpitis or
inflammation confined to the coronal pulp are considered candidates for vital pulp
therapy. Primary teeth presenting with irreversible pulpitis, pulp necrosis or radicular
pulp inflammation are not candidates for vital pulp therapy as widespread inflammation
! 33!
may negatively affect pulp therapy outcomes.
Clinicians are able to predict which primary teeth are candidates for vital pulp therapy
with relative accuracy using a combination of clinical signs and symptoms and
radiographic signs. However, there is not always a good correlation between individual
clinical signs and symptoms and radiographic signs and the histopathological condition
of the pulp.
Clinical findings that may aid in diagnosis of pulp status include location of the carious
lesion, presence of pulp exposure, presence of swelling, presence of fistula/sinus tract,
tenderness to tooth percussion, tooth mobility, abnormal responses to sensibility tests,
degree of pulpal bleeding and color of exposed pulp tissue. Presence of swelling,
fistula/sinus tract, excessive hemorrhage upon carious pulp exposure and/or dark red or
purple bleeding upon coronal pulp amputation are strongly correlated with radicular pulp
inflammation or necrosis. Bleeding time is routinely used in the diagnosis of pulp status,
however evidence demonstrates bleeding time is an unreliable indicator of pulpal therapy
outcome.
Radiographic signs that contraindicate vital pulp therapy in primary teeth include the
presence of furcation or periapical radiolucencies, external root resorption, internal root
resorption or widened PDL. PCO can be a pathophysiological process that does not
necessitate treatment in the absence of signs or symptoms of infection.
! 34!
7. Vital pulp therapy
Primary teeth with the diagnosis of reversible pulpitis are candidates for vital pulp
therapy. Vital pulp therapy is contraindicated in primary teeth with irreversible pulpitis
or necrotic pulps. Outcomes of pulp therapy are influenced by diagnosis, clinical
technique, choice of pulp medicament, restoration marginal seal and host immune
reaction. Treatment options of vital pulps with reversible pulpitis in primary teeth
include: indirect pulp therapy (IPT), direct pulp capping (DPC), pulpotomy, RCT and
extraction.
7.1. Indirect pulp therapy
Indirect pulp therapy is a procedure in which carious dentin surrounding the pulp is left in
place to avoid an anticipated pulp exposure in reversibly inflamed teeth.90 In IPT, the
carious dentin at the periphery of a carious lesion is removed, a medicated liner is placed
over the residual carious dentin and the tooth is restored. Placement of a liner and sealing
with a restoration stops the progression of the caries process within the carious lesion.91,92
Indirect pulp therapy also relies on the repair and healing potential of a vital pulp to
remove existing cariogenic bacteria and stimulate new hard tissue formation adjacent to
the carious lesions. Variations in the IPT technique include extent of caries removal,
quantity and quality of remaining carious dentin, single versus multiple appointment(s),
complete versus partial caries removal and choice of restorative material and liner.
There is currently no consensus with regards to the proportion of caries that should be
removed and quality of dentin that should remain for IPT. There is evidence that the
! 35!
restoration marginal seal is a greater factor in IPT outcomes than the debridement of
caries. In IPT, the substrate or source of nutrition for cariogenic bacteria is eliminated
through sealing of carious dentin. Thus, the number of cariogenic bacteria decrease and a
shift towards a less cariogenic flora occurs.93-95 The decrease in cariogenic bacteria and
flora shift eventually leads to the arrest of the caries process.96-98 Type of lining material
does not affect IPT outcomes as high rates of acceptable outcomes in IPT have been
demonstrated regardless of liner type used.99,100
Indirect pulp therapy can be performed as a one-step (ultraconservative) approach where
a permanent restoration is placed immediately after IPT or as a two-step (step-wise)
approach where an intermediate restoration is placed after IPT and the tooth is reentered
at a later date for placement of a definitive restoration. Currently, there is no consensus
on the preferred technique. Both one- and two-step procedures have shown favorable
clinical outcomes in retrospective trials.99,101-104
Pulpotomy is the most commonly taught pulp therapy technique for asymptomatic vital
primary molars followed by IPT.105 Prospective and retrospective studies have reported
IPT acceptable outcome rates between 73 and 95 percent.101-103,106-110 Indirect pulp
therapy is demonstrating promising results in regards to pulp therapy outcomes, however
a limited body of literature exist to support IPT compared to pulpotomy and only 1 weak
low-level study has directly compared IPT and pulpotomy in primary teeth.102 The
retrospective study assessed 133 primary molars treated with IPT or formocresol (FC)
pulpotomy. Of 55 IPT treated molars, 93 percent of molars demonstrated acceptable
! 36!
outcomes over a 5-year period. Of 78 FC pulpotomy treated molars, 74 percent
demonstrated acceptable outcomes over a 5-year period. The study demonstrated IPT
had superior outcomes to FC pulpotomy however the level of evidence was weak. The
study did not standardize restorations and the time frame in which treatment was
performed between the 2 groups.102 A proportion of FC pulpotomy treated molars were
restored with Interim Restorative Material (IRM) where the acceptable outcome rate was
39 percent. As well, all pulpotomies were performed between 1970 and 1990 while all
IPT treatments occurred after 1990 by predominantly a single practitioner. Based on this
investigation, there is inadequate evidence to indicate IPT is superior or even equivalent
to FC pulpotomy.
The majority of clinicians prefer pulpotomy to IPT.105 Reasons why clinicians may
prefer pulpotomy to IPT are familiarity, there is a greater body of literature investigating
pulpotomy and more clinicians were trained in pulpotomy than IPT.105 Many clinicians
argue that the pulp may be diseased beneath carious lesions where healing and repair of
the pulp may not be possible. Evidence suggests deep caries, in particular proximal
lesions, may present with extensive inflammation and pulpotomy would ensure the
removal of inflamed pulp tissue leaving only vital and uninflamed radicular tissue with
the potential for healing and repair.75
7.2. Direct pulp capping
Direct pulp capping is the placement of a medicated base in direct contact with carious,
traumatic or mechanically exposed pulp tissue. Direct pulp capping in primary teeth has
! 37!
demonstrated poor outcomes.111-114 The most common sequelae of unacceptable
treatment outcomes of DPC are abscess and internal root resorption.111,115,116 Calcium
hydroxide (Ca(OH)2) is the most common DPC medicament used. A randomized
controlled trial reported clinical and radiographic acceptable outcome rates of Ca(OH)2
DPC treated molars were 62 and 53 percent at 24 months post-treatment.117
7.3. Pulpotomy
Pulpotomy is the amputation of coronal pulp tissue often followed by the placement of a
medicament on the remaining vital radicular pulp tissue.90 The pulpotomy is the most
widely used and taught vital primary pulp therapy technique by pediatric dentists in
North America.105,118,119 The pulpotomy is the accepted standard of care for carious
exposures of primary molars with reversible pulpitis. However, there is currently no
accepted standard of care for primary incisors with reversible pulpitis.
Pulpotomy techniques are categorized broadly into 3 groups: devitalization, preservation
and regeneration.120 Devitalization techniques include FC, gluteraldehyde, electrosurgery
and laser pulpotomy. Preservation techniques include ferric sulphate (FS), sodium
hypochlorite (NaOCL) and ZOE pulpotomy. Regenerative techniques include Ca(OH)2
and MTA pulpotomy. Regardless of the pulpotomy technique, the radicular pulp should
remain asymptomatic without signs or symptoms of pain or infection.
7.4. Formocresol pulpotomy
The FC pulpotomy is the most common technique taught in dental schools and used by
! 38!
pediatric dentists in North America.105 The most common formulation of FC is 35
percent cresol, 19 percent formaldehyde and 15 percent glycerin in an aqueous solution.
The active ingredients in FC are formaldehyde and cresol. Formaldehyde is a tissue
fixative and prevents tissue autolysis through the formation of stable molecular
crosslinkings resistant to breakdown. Cresol is antimicrobial, cytotoxic and able to
emulsify with formaldehyde.121 The glycerin in FC acts as a vehicle for the
formaldehyde and cresol as well as an emulsifying agent preventing the polymerization
of the formaldehyde.122
7.4.1. Formocresol pulpotomy technique
The most common FC pulpotomy technique used is coronal pulp amputation followed by
hemostasis with pressure using moist cotton and then application of FC on a cotton
pellet.105 The application of FC on the remaining pulp tissue ranges from 1 to 5 minutes.
Variations in FC application that ranged between 1 and 5 minutes did not affect clinical
or radiographic outcomes.123,124 Longer applications of FC were associated with poorer
clinical and radiographic outcomes125-127 and complete loss of pulp tissue vitality with
formation of fibrous granulation tissue.128 Variations in the FC pulpotomy technique
include modifications to the concentration of FC,129-131 number of appointments involved
in treatment,132 application time of FC,124,131 type of base used127 and pressure hemostasis
with or without the use of a FC dampened cotton pellet.124,133
Full strength FC is the most commonly used form of FC used by pediatric dentists for
pulpotomy. The second most commonly used form of FC used by pediatric dentists is a
! 39!
1:5 dilution of full strength FC. Full strength FC and 1:5 dilution of FC have
demonstrated similar clinical, radiographic and histological outcomes.134
7.4.2. Effect of formocresol on pulp histology
Full-strength FC applied to vital pulp tissue for 5 minutes produces 3 distinct histological
zones within the pulp. The 3 zones that develop are the zone of fixation
(eosinophilic/acidophilic zone), the pale staining zone (an area of poor cellular definition
and marked by a reduction in cells and fibers) and the zone of inflammation.123,126,127 In
general, pulp tissue in contact with FC is devitalized through fixation. The fixative effect
diminishes apically as pulp tissue in the apical third is often normal and retains its
vitality.135
The most common histopathological finding of FC pulptomy treated primary molars is
chronic inflammation.136 However, histological findings in FC pulpotomy treated molars
range from normal pulp tissue to complete necrosis of the pulp. The pulp status of 22
primary molars were assessed histologically 3 to 5 years after FC pulpotomy.136 All teeth
that underwent histological assessment were deemed to have acceptable clinical and
radiographic outcomes at the time of extraction. The study demonstrated a wide variation
in pulp histology that ranged from normal pulp tissue to complete pulp necrosis. Of the
22 molars assessed, 10 molars presented with chronic inflammation, 7 with normal pulp
tissue, 4 with partial necrosis and 1 with complete necrosis. Overall, 95 percent of
primary molars treated with FC pulpotomy in this investigation remained vital though
chronic inflammation was a common finding.128 Despite the range of histological
! 40!
findings, the majority of FC pulpotomy treated teeth are not associated with pain or
infection.
7.4.3. Formocresol pulpotomy outcomes: clinical trials, systematic reviews, and
meta-analyses
The clinical outcomes for FC pulpotomy reported have ranged from 87 to 100 percent
and the radiographic outcomes have ranged from 56 to 100 percent over follow-up
periods from 6 to 74 months (Appendix 1A). FC pulpotomy demonstrates superior
clinical and radiographic outcomes compared to Ca(OH)2 and equivalent clinical and
radiographic outcomes to FS, laser and electrosurgery.137,138 MTA demonstrates superior
radiographic outcomes when compared to FC.84,139-145 The most common reported
pathological radiographic finding of FC pulpotomy was internal root resorption.
7.4.4. Formocresol concerns
Concerns regarding the safety of FC include the allergenic, irritant, mutagenic and
carcinogenic potential of formaldehyde. Adverse effects are primarily in the respiratory
and digestive tract system through inhalation and ingestion.146
Formaldehyde is an irritant and exposure to high concentrations of formaldehyde can
cause burning sensations in the eyes, nose and throat. Long-term exposure to moderate
formaldehyde concentrations is linked to adverse respiratory symptoms.147 Chronic low
levels of formaldehyde exposure were associated with irritation of the eyes and mucous
membranes and permanent respiratory impairment including signs and symptoms of
! 41!
chronic obstructive lung disease in both occupational and residential environments.148-150
No immune responses or allergic reactions against formaldehyde have been reported.151-
153
Formaldehyde is listed as a known human carcinogen by the International Agency for
Research on Cancer, Health Canada and The Agency for Toxic Substances and Disease
Registry in the United States Department of Health and Human Services.
Formaldehyde is listed as a known carcinogen based on sufficient evidence of
carcinogenicity from studies in humans and animals and data on biological mechanisms
of carcinogenesis.154-156 Formaldehyde can react covalently with amino and sulfhydryl
groups in DNA and form unstable DNA-protein crosslinks.157 The most common types
of DNA damage include sister chromatid exchanges, micronuclei and chromosomal
aberrations and deletions.158,159
Concerns have been expressed regarding the safety and use of FC in dentistry as systemic
spread of formaldehyde after pulpotomy has been reported.160 However, evidence
indicates FC pulpotomy procedures poses a minimal risk of cancer to children.161,162 The
plasma concentration of FC was analyzed in 30 children undergoing 85 primary tooth
pulpotomies.163 Preoperative and post-operative blood samples were taken at 5, 15, 30,
60, 90 and 120 minutes. Formaldehyde was undetectable above baseline physiologic
concentration. In another study, lymphocytes were assessed for chromosomal aberrations
in 20 children treated with FC pulpotomy.161 Two venous blood samples were collected
from each child, the first prior to FC pulpotomy (experimental group) and the second 24
! 42!
hours after pulpotomy (treated group). There was no statistically significant difference
between the experimental and treated groups with regards to chromosomal aberrations.
However, the results demonstrated FC pulpotomy induced severe chromosomal
aberrations in 1 patient. This was concerning to the authors as no cause was found.
Concerns have been expressed regarding the occupational exposure of dental professions
to formaldehyde in pediatric dentistry.160 Exposure of formaldehyde to dental
professionals with the regular use of FC pulpotomies has not been investigated. The
Canadian Labour Code acceptable occupational exposure limits for formaldehyde are an
average of 0.3 parts per million (ppm) over an 8-hour period and 1 ppm over a 15-minute
period.164 The National Institute for Occupational Safety and Health in the United States
has stated that formaldehyde may cause acute inhalation toxicity at concentrations of 20
ppm and higher.165 Discerning the occupational exposure to formaldehyde for dental
professionals is difficult and has not been assessed. Exposure to formaldehyde depends
on dose and type of FC used, distance from FC and length of exposure. Ambient levels
of formaldehyde were measured using an infrared spectrophotometer from FC within a
dental clinic.166 Measurements were taken over a 5-minute period at a distance of 46 cm,
to replicate the typical exposure distances for dental professionals, and 3 cm, to assess
close contact with FC. The formaldehyde ppm of a saturated no. 3 cotton pellet with
Buckley’s FC was 0.4 ppm at 46 cm and 7.56 at 3 cm. The formaldehyde concentration
of saturated no. 3 cotton with 1:5 dilution of Buckley’s was 0.14 at 46 cm and 1.52 cm.
At the typical exposure distance for dental professionals, dental professionals exposure to
formaldehyde are likely within the Canadian Labour Code acceptable occupational
exposure limits for formaldehyde. However, without the judicious use of formaldehyde,
! 43!
dental professionals may be at risk of overexposure to formaldehyde.
7.4.5. Formocresol pulpotomy summary
Formocresol is the most utilized pulpotomy agent in pediatric dentistry in North America,
however concerns regarding the mutagenic, carcinogenic and irritant properties of FC
have been reported. European clinicians have shifted away from the use of FC in
preference for alternative medicaments due to these concerns.167 Formocresol is an
effective pulpotomy agent with reported acceptable clinical outcomes ranging from 87
and 100 percent and acceptable radiographic outcomes ranging from 56 and 100 percent
at 6 to 74 months follow-up.
The International Agency for Research on Cancer has recommended the substitution of
formaldehyde containing materials for safer alternatives due to the potential mutagenic
and carcinogenic properties of formaldehyde in FC. As a result, alternative pulpotomy
medicaments to FC are being investigated. No significant differences in clinical and
radiographic outcomes were noted between FC when compared to FS, NaOCl, laser and
electrosurgery. Formocresol demonstrated superior clinical and radiographic outcomes to
Ca(OH)2 and inferior radiographic outcomes when compared to MTA pulpotomy.
7.5. Glutaraldehyde pulpotomy
Glutaraldehyde is an organic compound used to disinfect medical and dental equipment,
as it is an effective anti-microbial. Glutaraldehyde is a superior fixative, provides a more
stable protein bond, is less penetrating and is faster acting when compared to FC.168,169
! 44!
Organic impurities in glutaraldehyde vary and their presence can result in unpredictable
fixative properties.170 Buffering of glutaraldehyde improves tissue fixation when
compared to unbuffered solutions of glutaraldehyde,171 however buffered preparations
over time become unstable.170
Weak evidence has reported glutaraldehyde pulpotomy acceptable clinical outcome rates
between 82 and 98 percent and acceptable radiographic outcome rates between 76 and 79
percent 12 to 36 months post-treatment.172,173 No strong evidence exists to indicate
glutaraldehyde pulpotomy efficacy or equivalency to FC pulpotomy. Glutaraldehyde has
not become widely investigated or accepted as a vital pulpotomy medicament because
buffered preparations have a limited and unpredictable shelf-life.
7.6. Zinc oxide eugenol pulpotomy
Zinc oxide eugenol is used as a pulpotomy base, root canal filling and intermediate
restorative material in the primary dentition. Zinc oxide eugenol is available non-
reinforced or reinforced with polymethyl methacrylate.174 Zinc oxide is a filler with high
tensile and compressive strength175,176 and eugenol has anodyne and antibacterial
properties.177 The effectiveness of ZOE as base pulpotomy material is attributed to its
marginal seal and release of eugenol.178-180 The marginal seal of ZOE is comparable to
other polycarboxylate and non-eugenol temporary restorative materials. In cases of
restoration failure, the eugenol in ZOE may aid in slowing the progression of caries due
to its antibacterial properties.181 Zinc oxide eugenol is not stable in the presence of water
and after setting ZOE may release eugenol and minimal amounts of zinc through
! 45!
hydrolysis. Hydrolysis of the bonds between molecules of eugenol and zinc hydroxide
yield free eugenol and insoluble zinc hydroxide.179
Classically, ZOE has been used as a base material for pulpotomies. However, a few
studies have assessed ZOE as a pulpotomy base without the use of any other pulpotomy
medicament. Clinical and radiographic outcomes of ZOE pulpotomy were demonstrated
to be inferior to FC and MTA pulpotomy.128,182-184 Severe chronic pulpal inflammation,
internal root resorption and abscess are the most common reported cause of unacceptable
outcomes in ZOE pulpotomy. Abscess, inflammation and internal root resorption
associated with ZOE pulpotomy are speculated to be caused by the release of free
eugenol or presence of impurities in ZOE.85,97 Eugenol in direct contact with pulp tissue
is cytotoxic.181 Cellular respiration is depressed in human dental pulp cells and mouse
fibroblasts when in contact with eugenol.178 Impurities in eugenol are residual
compounds from the separation of eugenol from oil of cloves and/or degradation products
from aging eugenol.185,186 ZOE pulpotomy is not recommended for the treatment of
carious primary teeth with reversible pulpitis.
7.7. Ferric sulfate pulpotomy
Ferric sulfate is a hemostatic agent prepared by oxidizing ferrous sulfate with nitric acid
in the presence of sulfuric acid. It is used to obtain hemostasis in endodontic surgery,
control gingival hemorrhage and as a pulpotomy medicament. Ferric sulfate has a pH of
1. When FS comes into contact with blood, a dark brown or greenish brown coagulum
forms.187 The precipitation and agglutination of ferric ions and blood proteins
! 46!
mechanically occludes and seals cut blood vessels aiding in hemostasis.188 Commercial
FS preparations include an aqueous 15.5 percent FS solution (AstringedentTM), an
aqueous 21 percent FS solution (StasisTM) and a 20 percent FS gel (ViscoStatTM).
7.7.1. Effect of ferric sulfate on soft tissues
Prolonged contact of FS with vital soft tissues produced persistent inflammation and a
foreign body reaction. The effect of FS on osseous healing was assessed by applying FS
to osseous defects in rabbit mandibles.189 Defects were either filled with a 15.5 percent
FS solution until hemostasis was achieved and closed (experimental group) or closed
after physiologic clot formation (control group). Histological examination conducted 18
and 46 days after treatment of the defects demonstrated no inflammation in the control
group while the FS group demonstrated a foreign body reaction, delayed healing, acute
inflammation and abscess formation. However, the investigators did not rinse away
excess FS solution, remove the FS coagulum or standardize the volume of FS used.
Studies using a similar methodology, except for FS being rinsed away after a 5-minute
application in osseous defects, demonstrated no significant differences between healing
in the experimental and control groups.189,190 Thus, excess FS may delay healing in soft
tissue and should be removed after application to soft tissue.
7.7.2. Ferric sulfate pulpotomy outcomes: clinical trials, systematic reviews, and
meta-analyses
Reported acceptable clinical outcome rates for FS pulpotomy ranged from 78 to 100
percent at 24 months. Reported acceptable radiographic outcomes for FS pulpotomy in
! 47!
primary molars ranged from 61 to 100 percent with follow-up times ranging from 6 to 36
months (Appendix 1B). Ferric sulfate pulpotomy demonstrated superior outcomes to
Ca(OH)2 and laser pulpotomy and inferior outcomes to MTA pulpotomy, MTA/FS
pulpotomy and vital RCT.144,82,83,191,192 Ferric sulfate and FC pulpotomy have shown
equivalent outcomes.84,137,138,193 Survival probability determined from survival analysis
ranged from 0.62 to 0.90 at 3 years for FS pulpotomy-treated primary teeth.191,85
7.7.3. Ferric sulfate pulpotomy techniques
Two FS pulpotomy procedures have been described in literature. In one technique, 15.5
percent FS aqueous solution is burnished on the radicular pulp stumps after coronal pulp
amputation.82 After approximately 15 seconds, the FS is rinsed away. If hemostasis is
not achieved after the initial application of FS, the tooth is considered to have radicular
pulp inflammation and non-vital pulp therapy or extraction is indicated. If hemostasis is
achieved, a fortified ZOE mixture is used to seal the pulp chamber. The other FS
technique reported in literature is similar to the first technique described except
hemostasis is obtained using a cotton pellet with pressure prior to FS application.194 The
benefit of the first technique described over the second is clinical efficiency.
There have been no reports of preference or direct comparison between the two
techniques by clinicians to date. Studies that used the FS technique that did not achieve
hemostasis prior to FS application demonstrated radiographic outcomes between 59 to 74
percent with a follow-up ranging from 24 to 36 months and internal root resorption rate
between 17 and 55 percent.82,83,191,192 Studies that used the FS technique that did achieve
! 48!
hemostasis prior to FS application demonstrated radiographic outcomes ranging from 73
to 100 percent with a follow-up of 12 to 36 months and an internal root resorption rate
ranging from 1 to 11 percent.137,138,182,195,196 FS pulpotomies in which hemostasis was
achieved prior to FS application, appear to show more acceptable outcomes and less
reports of internal root resorption than FS pulpotomies where hemostasis was not
achieved prior to FS application. Whether this is a perceived or actual difference in
outcomes between the techniques is undetermined and requires further investigation.
7.7.4. Ferric sulfate pulpotomy and internal root resorption
Internal root resorption has been reported as the most common pathological finding in FS
pulpotomy outcome studies. The reported prevalence of internal root resorption of FS
pulpotomy has ranged from 5 to 55 percent (Appendix 1B). Reported internal root
resorption in primary teeth treated with FC pulpotomy has ranged from 4 to 17
percent.137,138,182,195,196
Three hypotheses for internal root resorption reported in FS pulpotomies have been
advanced. One hypothesis is that application of FS may prevent the accurate diagnosis of
the inflammatory state of the radicular pulp. As FS can cause the immediate hemostasis
of the cut radicular pulp stumps, the characteristics (e.g. color and extent) of the bleeding
might not be accurately assessed. However the ability to clinically assess pulpal bleeding
characteristics in FS pulpotomy is similar to other pulpotomy techniques such as FC
pulpotomy. The only characteristic that can not be assessed in a similar manner is
bleeding time which is an unreliable measure of pulp therapy outcome.60 A second
! 49!
hypothesis as to the cause of internal root resorption in FS pulpotomy treated teeth is
ZOE in direct contact with the radicular pulp causes inflammation that results in internal
root resorption. The direct contact of ZOE with radicular pulp can cause a chronic
inflammation that is postulated to lead to internal root resorption. Vital pulp tissue in
direct contact with ZOE and eugenol has been associated with moderate to severe
inflammatory responses.181,197 A third hypothesis for the increased rate of internal root
resorption in FS pulpotomies is ferric ions and ferric-blood coagulum results in
inflammation and causes internal root resorption.
Perforation of the root from internal root resorption can induce an inflammatory response
in the PDL and the surrounding bone and produce an unacceptable outcome.198 Some
instances of internal root resorption in FS pulpotomy were shown to be self-limiting or
remain asymptomatic and did not interfere with normal exfoliation.85,131 A prospective
clinical trial reported areas of internal resorption in FS pulpotomy treated primary molars
that remained unchanged over 34 months via radiographic follow-up.131 However, a
randomized controlled study demonstrated molars exhibiting internal root resorption on
post-treatment radiographic examination were significantly more likely to have an
unacceptable radiographic outcome (P<.0001;OR:9.90).83 Though internal root
resorption has the potential to arrest and not interfere with exfoliation, there is good
evidence to demonstrate internal root resorption is associated with unacceptable pulp
therapy outcomes.
! 50!
7.8. Sodium hypochlorite pulpotomy
Sodium hypochlorite is used as an endodontic irrigant in RCT. NaOCl aids in removing
coagulum, controlling hemorrhage, removing dentin chips and formation of dentin
bridged.199 A randomized controlled trial compared the clinical and radiographic
outcomes of 3 percent NaOCl and a 1:5 dilution of Buckley’s FC in primary molars of
healthy children.200 Both groups demonstrated 100 percent acceptable clinical outcomes
at 12-months. Radiographic outcomes at 12-months demonstrated 80 percent (12 of 15)
of NaOCl and 90 percent (9 of 10) of FC pulpotomy treated molars had acceptable
outcomes. No significant differences in clinical or radiographic outcomes were
demonstrated between NaOCL and FC at 12-months. Another randomized controlled
trial compared the clinical and radiographic outcomes of NaOCL, FC, FS and MTA
pulpotomy.195 No statistically significant differences in radiographic outcomes were
found among all the groups at 24 months of follow-up. However, both studies suffered
from large sample wastage over the follow-up period. Sodium hypochlorite pulpotomy
should not be considered an alternative to FC or FS pulpotomy.
7.9. Calcium hydroxide pulpotomy
Calcium hydroxide is a crystalline, highly alkaline and soluble basic salt. Though
frequently used in the permanent dentition, use of Ca(OH)2 in the primary dentition has
been controversial. Calcium hydroxide pulpotomy has frequently been associated with
the development of abscesses, chronic pulpal inflammation and internal root
resorption.201,202
! 51!
The clinical and radiographic outcomes of Ca(OH)2, FS and Er:YAG laser pulpotomy
were compared to FC pulpotomy over a 3-year follow-up period.137 Calcium hydroxide
pulpotomy was 3 times more likely to have an unacceptable outcome than FC pulpotomy
(P=.07; Wald chi square test). Formocresol and Ca(OH)2 pulpotomy were compared in a
similar study.138 Clinically acceptable outcomes after 24-months were reported in 96
percent of FC and 87 percent of Ca(OH)2 pulpotomy treated molars. Radiographically
acceptable outcomes after 24-months were 87 percent in the FC group and 53 percent in
the Ca(OH)2 group. Calcium hydroxide demonstrated inferior combined clinical and
radiographic outcome rates when compared to FC pulpotomy treated molars (P<.05,
Wald chi-square). A meta-analysis comparing MTA and Ca(OH)2 concluded MTA
demonstrated superior clinical and radiographic outcomes to Ca(OH)2.144 A statistically
significant difference was found between MTA and Ca(OH)2 outcomes with a relative
risk of 0.19 at 12-months and 0.38 at 24-months post-treatment.
The preponderance of evidence has demonstrated Ca(OH)2 pulpotomy outcomes are
inferior to FC and MTA.137,138,201-203 Calcium hydroxide is not recommended for use as a
pulpotomy medicament in vital primary teeth.
7.10. Vital root canal therapy in primary teeth
Vital RCT is the removal of coronal and radicular pulp tissue followed by obturation of
the root canal system.204 Unlike in the permanent dentition, shaping of the canals is not
performed. Common irrigation solutions include sterile water, NaOCl, hydrogen
peroxide or saline.205-212
! 52!
The ideal root canal filling material would be antimicrobial, easy to manipulate, easily
removed if necessary, resorbable at the same rate as the primary tooth root, biologically
safe, cost effective, radiopaque, adhesive to root canal walls, non-shrinking, non-soluble
and nontoxic to periapical tissues and undisruptive to the development and eruption of
succedaneous teeth.206,213 A variety of materials are used as obturation agents in primary
teeth. Among the most common are: ZOE, ZOE with FC, Ca(OH)2, Kri paste, Endoflas
and Vitapex. Zinc oxide eugenol is the most common obturation material used in RCT
for primary teeth.93,112,205,207,210,214-218
7.10.1. Vital primary root canal therapy outcomes: clinical trials, systematic
reviews, and meta-analyses
Evidence has reported acceptable clinical outcomes of vital RCT ranging between 96 to
100 and acceptable radiographic outcomes ranging between and 59 to 91 percent at 6- to
24-months follow-up (Appendix 1C). Vital RCT was reported to have comparable
outcomes to FC and FS pulpotomy.82,191,192,219 Though evidence has demonstrated
equivalent outcomes for vital RCT and FC pulpotomy in primary teeth, the technique has
not been widely accepted for the treatment of primary molars as it is more technically
challenging than pulpotomy and may require additional time to complete.
An association between RCT outcomes and degree of root fill in primary teeth has been
demonstrated.205,206,210,214,217,218,220,221 Primary teeth with canals that are overfilled have
poorer outcomes than teeth with canals filled to the apex or underfilled.214 The outcomes
of RCT primary teeth with canals underfilled, filled to the radiographic apex and
! 53!
overfilled were compared. Acceptable outcome rates were reported in 87 percent (32 of
37) of underfilled canals, 89 percent (16 of 18) of canals filled to the radiographic apex
and 58 percent (15 of 26) if overfilled canals. Overfilled canals demonstrated
significantly poorer outcomes than primary teeth that were underfilled or filled to the
radiographic apex (P=.011). The sample included both vital and non-vital primary teeth.
Another study showed incisors with gross overfill of the pulp canal with ZOE
demonstrated statistically significant more unfavorable outcomes than slightly overfilled,
underfilled and filled to the radiographic apex in primary incisors (P<.001).222
Obturation material extrusion beyond the apex should be avoided.
A variety of obturation techniques have been developed for primary teeth. Methods of
obturation include: pressure syringes, premixed syringes, lentulo spirals and endodontic
pluggers. Previous in vitro and in vivo studies of obturation methods in primary teeth
showed that the lentulo spiral performed equivalent to or better than other
techniques.210,213,220,223-226
7.10.2. Ectopic eruption of succedaneous teeth following primary root canal therapy
Retrospective studies have demonstrated an association between ZOE RCT and the
delayed exfoliation of the treated primary teeth, retention of obturation material prior and
after the exfoliation of primary teeth and ectopic eruption of succedaneous teeth205-
207,214,217 Retained ZOE particles have been observed in gingiva and alveolar bone,
however infections associated with retained ZOE have not been reported.205,207,214 Zinc
oxide eugenol obturation paste was retained in the gingiva in 73 percent (11 of 15) of
! 54!
subjects after exfoliation of RCT treated primary incisors.207
Incomplete resorption of ZOE is implicated in the deflection of erupting succedaneous
teeth. The reported prevalence of anterior crossbite in the early mixed dentition is 8
percent. However, the reported incidence of succedaneous teeth erupting into anterior
crossbite following primary incisor ZOE RCT is 20 percent.214,227 Thirty percent (24 of
81) of primary teeth treated with RCT are reported to require extraction because of
delayed exfoliation and over-retention. Retained ZOE may be related to non-resorbing
reinforcing agents in ZOE, such as silica.
There is limited evidence in the area of delayed exfoliation of primary teeth, retention of
obturation material prior and after the exfoliation of primary teeth and ectopic eruption of
succedaneous teeth. The studies are retrospective in nature with a small sample size.
Based on available evidence, RCT therapy may be associated with retention of ZOE
filling materials after the exfoliation of treated primary teeth and ectopic eruption of
succedaneous teeth.
7.11. Mineral trioxide aggregate pulpotomy
Mineral trioxide aggregate is a hydraulic silicate cement introduced by Torabinejad in
1993 and patented in 1995 as a root-end filling material.228 Since its introduction, MTA
has been used for pulp capping, pulpotomy, apical barrier formation in teeth with open
apices, repair of root perforations and root canal fillings.229 Reported uses of MTA in the
primary dentition have included use as a DPC, IPT and pulpotomy medicament.
! 55!
The composition of MTA powder varies among commercial products available, however
MTA powder is essentially a refined Portland cement (PC) with the addition of bismuth
oxide, a radiopacifier. The principal constituents in MTA are tricalcium silicate and
dicalcium silicate. Mineral trioxide aggregate powder may also contain varying smaller
amounts of tricalcium aluminate, tricalcium oxide, silicate oxide, gypsum and bismuth
oxide with the proportion of constituents varying among commercial products.229
Mineral trioxide aggregate is commercially available in several forms. Commercially
available MTA products, at the time of writing, are listed in Table 2.
Clinkers are irregular lumps produced by sintering various minerals during the cement
kiln stage. Mineral trioxide aggregate powder is formed from clinkers made of various
raw minerals including lime, silica, aluminum oxide and ferric oxide. The constituents
and their proportions may vary based on raw materials and clinker process used to form
the MTA powder. Though chemical compositions and setting times may vary between
types of MTA, the majority of physical and chemical properties between the various
forms are not significantly different.229 MTA Bio is an MTA-based material that is fully
synthesized in laboratory. According to the manufacturer, the goal of this new
formulation is to avoid the presence of arsenic, which is detected in other MTA-based
materials and PC.
7.11.1. Mineral trioxide aggregate chemical properties
The addition of water to MTA powder results in a colloidal gel that solidifies to a hard
structure within 14 minutes to 2 hours and 40 minutes depending on the type of MTA.229
! 56!
A unique advantage of MTA compared to other traditional materials such as composite or
glass ionomer is that the setting of MTA is not adversely affected by the presence of
water. However, the presence of blood or serum during setting of MTA can alter the
physical and chemical properties of MTA. The surface of MTA, when set in water,
shows a crystalline structure while the surface of MTA set in fetal bovine serum (FBS),
saliva or fresh blood demonstrates the absence of a crystalline structure.230,231 Proteins in
saliva and/or blood may prevent the complete hydration and setting of MTA. In vitro,
blood and serum interfered with the setting of MTA, whether this finding is clinically
significant is undetermined at this time. When preparing and using MTA, blood and
saliva contamination should be minimized as contamination could compromise the
chemical and physical properties of MTA.
Mineral trioxide aggregate when placed adjacent to dentin forms hydroxyapatite. When
MTA powder is mixed with water, calcium and Ca(OH)2 are formed. Hydroxyapatite
forms from Ca(OH)2 and calcium released from MTA and phosphate and hydroxyl ions
from body fluids.232-234 The morphology of the hydroxyapatite at the dentin-MTA
interfaces will vary depending on the pH and calcium/phosphate ratio.235
MTA powder exposed to moisture can compromise the chemical set of MTA when
mixed at a later time. Therefore, once a sachet of MTA powder is opened, the unused
powder can be used up to 4 weeks later, provided it is stored in a water and airtight
container.236
! 57!
7.11.2. Mineral trioxide aggregate physical properties
Physicals properties of MTA investigated have included solubility, particle size, pH, seal
and expansion.229 The majority of evidence reports low or no solubility for MTA.228,237-
239 Higher water-to-powder ratios increases MTA solubility and porosity. Excess
condensation pressure and/or dry storage conditions decrease the compressive strength of
MTA.240-242 Greater condensation pressure results in fewer voids and microchannels
reducing water uptake that hinders MTA setting.242 Dry storage conditions delay the
complete set of MTA.240
Set MTA particle sizes range from 1 to 10 µm243 whereas MTA powder particles prior to
mixing with water range from 1 to 30 µm.244 Some MTA particles are as small or smaller
than the diameter of dentinal tubules (~1.5 µm). The size of MTA particles may aid in
the sealing ability of MTA.245 This hypothesis may not be clinically relevant as dentinal
tubules after root canal preparation are not open unless the smear layer is removed.
Mineral trioxide aggregate is alkaline and the pH of MTA rises from 10.5 to 12.5
approximately 3 hours after mixing.246 This pH rise is due to the formation of Ca(OH)2
during the hydration process. The pH of MTA declines overtime but has been
demonstrated to maintain an alkaline pH value throughout a 78 day observation period.247
Dye leakage, bacterial leakage and fluid infiltration studies have shown that MTA has a
better seal and less microleakage when compared to traditional materials such as
amalgam, GI cement and ZOE.248 The sealing ability of MTA is speculated to be
attributed to the formation of hydroxyapatite precipitates at the MTA-dentin interface
! 58!
leading to a chemical bond between MTA and dentin.249-252 These hydroxyapatite
precipitates at the MTA-dentin interfacial space extend into the dentinal tubules and form
tag-like structures.233 These tag-like structures are speculated to be the result of calcium
ions released from MTA that diffused through dentinal tubules and react with phosphate
ions in the tissue fluid eventually yielding hydroxyapatite.249 MTA also undergoes slight
expansion upon setting, which may contribute to its sealing ability.253,254
7.11.3. Mineral trioxide aggregate antimicrobial properties
Mineral trioxide aggregate may be considered to have an indirect antimicrobial effect
because of its sealing properties and resultant limited microleakage. However, MTA may
have limited benefit as a direct antimicrobial despite its alkaline pH. Mineral trioxide
aggregate demonstrates no antimicrobial activity against anaerobes, which predominate
the majority of flora found in root canals, but did have some effect on some facultative
bacteria.255
7.11.4. Effect of mineral trioxide aggregate on soft tissues
Subcutaneous tissue response to MTA is characterized by mild to moderate inflammation
that resolves within 30 days.256-259 In a rat study, investigators assessed the histological
response of subcutaneous tissue to MTA, Ergeo CPM, another form of commercially
available MTA, and a control group where only a polyethylene tube was implanted.260
Mild chronic inflammation was observed in the MTA and CPM groups after 7 and 14
days. At day 30, no difference was found between all groups as all groups presented with
a similar mature fibro-collagen tissue and minimal inflammation.
! 59!
7.11.5. Mineral trioxide aggregate hard tissue formation properties
Mineral trioxide aggregate induces and conduces dentin, bone and cementum formation.
It is associated with the up-regulation of various types of cytokines and biologic markers
associated with proliferation and differentiation of progenitor cells, odontoblastic
activity, matrix formation and mineralization.261,262 MTA releases Ca(OH)2 and calcium
that stimulates the proliferation of human dental pulp cells263 and is speculated to trigger
the differentiation of odontoblast-like cells in the dental pulp,264 resulting in production
of mineralized tissue. Calcium and Ca(OH)2 also interact with phosphate-containing
fluids to form apatite precipitates.265
The ability of MTA to induce reparative dentinogenesis or dentin bridge formation has
been demonstrated in animal and human studies in which DPC or pulpotomy was
performed on mechanically or cariously exposed pulps.261,266-275 As a pulp capping agent,
MTA demonstrated greater dentin bridge formation and less porous dentin bridges when
compared to Ca(OH)2 in histological studies.266,269,270,273,276,277 Results may be explained
by the superior seal, lower solubility, ability to stimulate more signaling molecules and
greater release of calcium ions of MTA when compared to Ca(OH)2.263,276,278
The association between MTA and dentinogenesis may be predominantly related to the
release of calcium by MTA. MTA releases significantly more calcium ions than
Ca(OH)2.263 When a similar amount of calcium (0.3 mmol/L) released by MTA was
added to dental pulp cells, in the absence of MTA, cellular proliferation activity was
similar to that observed with MTA. The study concluded that the continuous release of
! 60!
calcium ions from MTA was associated with proliferation of human dental pulp cells.263
7.11.6. Mineral trioxide aggregate properties to adjacent restorative materials
An in vitro study demonstrated that partially set MTA continues to set to completion
when GI cement is placed over MTA.279,280 The setting of MTA and GI cement are
unaffected by the presence of the one another and the GI cement demonstrates no signs of
dehydration.279 Composite resin restorations do not affect the setting of MTA when
placed adjacent.280 However, compressive strength of MTA is significantly decreased
when MTA is etched with 37 percent phosphoric acid within 4 hours of mixing versus 96
hours after mixing.281 When placing acid-etch composites adjacent to MTA within 96
hours of mixing, acid etching of MTA should be minimized as etching could compromise
the chemical and physical properties of MTA. An intermediate layer of GI cement can be
placed to prevent contact between the MTA and acid-etch.
7.11.7. Mineral trioxide aggregate concerns
The carcinogenic and mutagenic potential of MTA was assessed in multiple studies.248
MTA is a non-carcinogenic and non-mutagenic material.248 The Ames mutagenicity test
demonstrated that MTA is not mutagenic.
The cytotoxicity of MTA was assessed by measuring various cellular parameters (e.g.
proliferation and viability) of different cells in direct or indirect contact with MTA. The
cytotoxicity of set MTA, when compared to other common restorative materials, is less
than amalgam, Super EBA and IRM. Cells in contact with set MTA showed higher
! 61!
viability and proliferative activity than amalgam, Super EBA and IRM.282 However,
MTA in a freshly mixed state demonstrates a higher cytotoxicity than amalgam, Super
EBA and IRM.283
The presence of heavy metal contaminants in MTA is a concern. These heavy metals
include chromium, lead and, in particular, arsenic. Arsenic is a natural component of the
earth’s crust and is widely distributed throughout the environment including in the air,
water and land. Humans are exposed to elevated levels of inorganic arsenic through
drinking contaminated water, using contaminated water in food preparation and irrigation
of food crops, industrial processes, eating contaminated food and smoking tobacco. Fish,
shellfish, meat, poultry, dairy products and cereals can also be dietary sources of arsenic,
although exposure from these foods is generally much lower than exposure through
contaminated groundwater.284
The International Agency for Research on Cancer (IARC) has classified arsenic and
arsenic compounds as carcinogenic to humans.285 A review of the latest scientific
evidence conducted in 2010 by the Joint Food and Agriculture Organization of the United
Nations (FAO) and World Health Organization Expert Committee on Food Additives
(JECFA) determined the lower limit/benchmark dose for a 0.5 percent increased
incidence of lung cancer (BMDL0.5) from epidemiological data was 3.0 µg/kg body
weight per day (2 to 7 µg/kg body weight per day based on the range of estimated total
dietary exposure). The current recommended limit of arsenic in drinking-water is 10
µg/litre.286
! 62!
The amount of arsenic ion released in ProRoot MTA and Angelus MTA were compared
and both materials release similar amounts of arsenic at values that were not harmful to
the human body and well below the tolerable arsenic levels found in drinking water.287
Mineral trioxide aggregate has been approved by the U.S. Food and Drug Administration
(FDA) since 1998.288
The clinical use of ProRoot MTA is safe in terms of its heavy metal contents.289,290 One
gram of ProRoot MTA and Tooth-colored ProRoot MTA contains minimal amounts of
arsenic, approximately 0.003 µg and 0.002 µg. MTA is a hardened bound material with
low solubility therefore minimal heavy metal ions are released from the cement.
7.11.8. Mineral trioxide aggregate discoloration
According to the manufacturer and various clinical reports, a gray color change of
ProRoot MTA is to be expected.291 Discolored MTA may cause teeth to change in color
or show through restorations and effect esthetics. Manufacturer’s instructions
recommend that MTA materials should not be used in visible areas (e.g. above crestal
bone level). Case reports have described coronal tooth discoloration associated with
Tooth-colored ProRoot MTA292,293 although a single case report demonstrated
discoloration was reversible with removal of MTA and bleaching.294 The cause and
mechanism of MTA discoloration is currently unknown. Speculations to the cause of
discoloration of Tooth-colored ProRoot MTA include the presence of iron, contamination
of MTA with blood and formation of black metallic bismuth under light irradiation.
! 63!
The presence of iron in ProRoot MTA is speculated to cause the gray discoloration of
MTA. Due to the concern of discoloration of ProRoot MTA, Tooth-colored ProRoot
MTA was introduced where the iron content was substantially less than ProRoot
MTA.291,295 However, Tooth-colored ProRoot MTA also demonstrates gray discoloration
in both in vivo and in vitro studies.296-298
MTA discoloration could also be attributed to the interaction between red blood cells and
setting MTA. The mechanism of MTA discoloration is hypothesized to be similar to the
discoloration of traumatized teeth where the hemolysis of erythrocytes and the
accumulation of hemoglobin and hematin molecules get embedded in dentin tubules.
The slow setting process of MTA may permit the absorption and subsequent hemolysis of
erythrocytes from the adjacent pulp tissue thus resulting in MTA discoloration.
However, MTA discoloration occurs in the absence of blood.298,299 The presence of red
blood cells exacerbates the discoloration of MTA.300 An in vitro study demonstrated the
presence of blood within the root canal adjacent to setting MTA exacerbated the
discoloration of MTA when compared to the setting MTA in the absence of blood
(P=.03). The mechanism by which blood exacerbates MTA discoloration is currently
unknown.
Watts et al., while assessing the effects of pH and mixing agents on setting of MTA in
vitro, found that all MTA specimens (regardless of mixing agent, pH, or time) turned
gray after 3 days (Figure 4).298 Portions of MTA exposed to phosphate buffered saline
(PBS) remained light in color. All MTA specimens that discolored were placed into PBS
! 64!
solution and MTA specimens displayed fading of the discoloration throughout the 28-day
trial on the exterior portion of the MTA specimens. The internal portions of the
specimens upon fracture remained dark. The study indicated that discoloration decreased
when MTA was exposed to anaerobic PBS environment.
Valles et al. conducted a pilot study in which Tooth-colored ProRoot MTA was sealed in
test tubes and half were saturated with pure oxygen while the other half was saturated
with pure nitrogen to simulate an oxygen-free environment.301 The surface color of the
oxygen-saturated samples changed from white to gray after exposure to curing light
irradiation, however, the color of the nitrogen-saturated samples remained stable.
Valles et al. evaluated the color stability of MTA after irradiation with 3 different curing
lights and with a fluorescent lamp in an oxygen-free environment.302 Thirty samples of
MTA were divided into 4 experimental groups (Optilux curing light, Bluephase curing
light, Demi curing light and fluorescent lamp) and 1 negative control group where the
sample was exposed to no light. The samples in the curing light groups were immersed
in glycerine to facilitate an oxygen-free environment. All the groups eventually
demonstrated discoloration except for the negative control group at all time intervals
(P>0.05) (Figure 5). No differences were observed between the fluorescent lamp and the
negative control group at day 1. However, after 5 days, the fluorescent lamp group also
displayed darkening of the sample surface similar to the other 3 experimental groups.
MTA contains 20 percent bismuth oxide and is added to MTA to enable its differentiation
! 65!
from adjacent structures on radiographs. The investigators speculated discoloration of
MTA is secondarily caused by the formation of metallic bismuth under light irradiation.
Bismuth oxide undergoes a thermal dissociation under high temperature resulting in
metallic black bismuth and oxygen.303 The reduced black crystals of bismuth could be
responsible for the darkening of MTA. The presence of these black crystals were
identified on X-ray diffraction in discolored MTA.304 Bismuth oxide can be excited by
heat or light and turn bismuth oxide dark in an oxygen-free environment.305 However,
bismuth oxide remains stable when heated or irradiated in the presence of oxygen.305
Oxygen is speculated to inhibit the formation of metallic bismuth however the exact
mechanism is unknown. One explanation may be the partial pressure of oxygen at high
temperature prevents formation of metallic bismuth.302 Another possible explanation is
oxygen absorbs the energy from light instead of the bismuth oxide or the bismuth oxide
once excited reacts with oxygen instead of remaining in its reduced black state.306 Either
way, oxygen appears to act as a quencher that quickly deactivates the excited state of
bismuth oxide, preventing a light-induced discoloration of MTA.301
In a follow-up study, the authors assessed the influence of light irradiation and oxygen on
the color stability of Tooth-colored ProRoot MTA, MTA Angelus White, white PC, PC
with the addition of bismuth oxide and Biodentine.301 Biodentine is a calcium silicate-
based material with similar properties to MTA composed mainly of tricalcium silicate,
calcium carbonate, zirconium oxide and calcium chloride. Each material was exposed to
various light conditions and an oxygen and oxygen-free environment. A
spectrophotometer was used to determine the color of each specimen at 0 seconds, 120
! 66!
seconds and 5 days. All materials with bismuth oxide (Tooth-colored ProRoot MTA,
MTA Angelus White and PC with the addition of bismuth oxide) demonstrated dark
discoloration after light irradiation in an oxygen-free environment when compared to
Biodentine and PC (P<.05, ANOVA). Groups exposed to no light or to an atmospheric
oxygen environment demonstrated color stability. PC and Biodentine maintained color
stability in all conditions over time and showed no significant differences in color when
compared to one another (P>.05). This study demonstrated in an oxygen-free
environment, irradiation with a light cure or fluorescent lamp and the presence of bismuth
oxide altered calcium silicate based materials leading to color changes.
The mechanism of MTA discoloration is still not fully understood, but recent evidence
suggests tooth discoloration is associated with metallic black bismuth oxide formed from
the reaction of bismuth oxide with light in a non-oxygenated environment. Discoloration
of MTA may not be a concern in the future as manufactures are distributing MTA where
zirconium oxide has replaced bismuth oxide as a radiopacifier. Also, alternative
materials are being manufactured and distributed (e.g. BioDentine and PC) that have
similar properties to MTA and are color-stable.
7.11.9. Mineral trioxide aggregate pulpotomy techniques
Two MTA pulpotomy techniques have been described in literature. The technique most
reported on is coronal pulp amputation, followed by pressure with a cotton pellet to
obtain hemostasis and finally placement of MTA over the radicular pulp stumps. The
cotton pellet is placed with pressure between 1 and 5 minutes until hemostasis is
! 67!
achieved.
To improve clinical and time efficiency, Doyle et al., described an alternative technique
in which FS was applied for 10 to 15 seconds after coronal pulp amputation to achieve
hemostasis prior to the placement of MTA.83 The application of FS allows for
hemostasis to be achieved within 10 to 15 seconds and was adapted from FS pulpotomy
techniques previously described in the literature 83,131,191. Ferric sulfate application prior
to MTA placement did not alter clinical or radiographic outcomes for MTA primary
molar pulpotomies (P>.05).83
7.11.10. Mineral trioxide aggregate pulpotomy outcomes: clinical trials, systematic
reviews and meta-analyses
The clinical acceptable outcomes for MTA pulpotomy reported have ranged from 97 to
100 and radiographic acceptable outcomes for MTA pulpotomy have ranged from 67 to
100 percent over follow-up periods between 6- to 74-months (Appendix 1D). MTA
pulpotomy demonstrates superior radiographic outcomes when compared to FC, FS,
Ca(OH)2, laser and ZOE pulpotomy.83,84,139-143,182 The most common radiographic
finding associated with the MTA pulpotomy was PCO.
Lin et al., in a systematic review and meta-analysis, compared clinical and radiographic
outcomes of different pulpotomy medicaments in primary molars.144 Thirty-seven
studies were included in the systematic review and 22 in the meta-analysis. The study
concluded MTA pulpotomy demonstrated superior radiographic outcomes to FC and FS
! 68!
pulpotomy at 18 to 24 months. MTA pulpotomy also demonstrated clinical and
radiographic outcomes superior to Ca(OH)2 and laser pulpotomy. Shirvani et al.
compared MTA and FC pulpotomy in a systematic review and meta-analysis.145 The
results demonstrated MTA outcomes were superior to FC outcomes in primary molar
pulpotomy. The relative risks of an unacceptable outcomes in FC pulpotomy was 2.7
times at 12 months and 2.4 times at 24 months when compared to MTA pulpotomy.
Anthonappa et al. in a systematic review evaluated the current evidence to support the
long-term effectiveness of MTA as a pulpotomy medicament in primary molars.307 The
study concluded that there was no evidence that MTA pulpotomy was superior to FC
pulpotomy due to low-quality evidence.308 A weakness of the study was the use of a
‘modified standard assessment criteria’ scale developed from Curzon & Toumba. This
scale has not been subjected to validity and reliability testing and was initially devised to
assess restorations in primary teeth.309 Without the use of an appropriate quality scale,
the results and conclusion of the study may be biased and not representative of the
existing evidence.
7.11.11. Mineral trioxide aggregate and portland cement
Mineral trioxide aggregate is a refined form of PC. The most common use of PC is the
production of concrete. Portland cement and MTA have similar major constituents.254
Clinical and radiographic outcomes of MTA and PC pulpotomy in primary teeth were
demonstrated to be similar in a single weak randomized control trial with a small
sample.310 Despite the similarities between PC and MTA, PC has not been used routinely
in humans. Concerns include its heavy metal contents, lack of a radioopacifier,
! 69!
comparatively larger setting expansion, relatively high solubility increasing the release of
heavy metals in some forms and lack of Health Canada and US federal approval for
clinical use.254,287,311-313 Portland cement is manufactured worldwide and controlling the
quality, composition and biocompatibility of various forms of PC would be a significant
challenge.314
7.11.12. Summary of mineral trioxide aggregate review
MTA pulpotomy has demonstrated superior radiographic outcomes compared to the FC,
FS, laser, Ca(OH)2 and ZOE pulpotomy. MTA has low solubility, good seal and induces
hard tissue formation. Drawbacks of MTA include its discoloration of treated teeth and
short-term storage capacity once exposed to moisture.
8. Outcome assessment of vital pulp therapy in primary teeth
Multiple opinions regarding criteria for acceptable and unacceptable vital pulp therapy
outcomes have been reported and debated in literature. Clinicians agree that clinical
signs or symptoms of persistent or spontaneous pain, soft tissue swelling, fistula/sinus
tract, tenderness to percussion or pathological tooth mobility are considered an
unacceptable outcome of vital pulp therapy. There is also consensus among authors that
radiographic signs of furcation or periapical radiolucencies or external root resorption are
unfavorable outcomes of vital pulp. However, clinicians have disputed whether or not
widened PDL, mobility, PCO and internal root resorption should be considered
unacceptable outcomes of vital pulp therapy.
! 70!
Outcome assessment based on widened PDL or mobility has not been reliable. A
widened PDL on radiographic exam may be representative of inflammation or infection
associated with irreversible pulpitis and necrotic pulps. However, trauma may also cause
inflammation and widening of the PDL. Also, accurate assessment of a widened PDL on
a radiograph may not be reliable as it is dependent on subjective assessment by a
clinician, radiographic technique and patient cooperation. A randomized controlled trial
demonstrated widened PDL was not associated with unacceptable outcomes in molars
treated with vital pulp therapy (P=.99; OR:1.01).83 Mobility in primary teeth can be
representative of a dental abscess or pathological root resorption, however assessment of
mobility in primary teeth by clinicians can be subjective even with the use of scales. As
well, mobility can be associated with a number of causes such as trauma, infection,
pathological root resorption and physiological root resorption.
Investigators have disputed whether or not the presence of internal root resorption is an
unacceptable treatment outcome. Some authors have considered internal root resorption
an unacceptable outcome of pulp therapy only if the internal root resorption is
progressive and/or perforation of the root canal system occurs.131,198,315,316 A randomized
controlled trial demonstrated molars exhibiting internal root resorption on post-treatment
radiographic examination were significantly more likely to have an unfavorable
radiographic outcome (P<.0001; OR:9.90).83 Though internal root resorption has been
associated with unacceptable outcomes, internal root resorption has not been designated
an unacceptable outcome or failure in multiple studies.82,83,85,191,192,203,316-318 Clinicians
often monitor internal root resorption in the absence of signs and/or symptoms of
! 71!
infection as primary teeth with internal root resorption may remain quiescent until their
exfoliation.
PCO results from odontoblastic activity and deposition of hard tissue along the wall of
the root canal within a vital pulp.83-86 A randomized controlled trial demonstrated molars
with evidence of PCO on post-treatment radiographs were significantly less likely to have
an unacceptable radiographic outcome (P=.0008; OR:0.08).83 Many investigators agree
that PCO results from odontoblastic activity within a vital pulp and is an acceptable
outcome of vital pulp therapy.83-86,219
Clinicians do not regard all radiographic pathological changes occurring after vital pulp
therapy as an indication for immediate extraction or non-vital pulp therapy as long as the
pulp treated tooth remains asymptomatic without extension of pathoses to supporting
structures. Offered a clinical scenario involving an 8-year-old healthy child presenting
with an asymptomatic primary molar 3 years post-vital pulp therapy with radiographic
evidence of pathologic root resorption, over 60 percent of predoctoral pediatric dentistry
program directors and pediatric dentists surveyed opted to observe the molar rather than
extract or provide primary RCT.105
Multiple radiographic outcome evaluations protocols have been developed and modified
by various investigators to distinguish between minor pathological changes that allow for
observation versus major pathological changes necessitating extraction or non-vital pulp
therapy.82,83,93,191,192,203,219,221,317,319 These radiographic evaluation methods were
! 72!
developed to simulate day-to-day clinical decision-making as clinicians are often
prepared to accept a limited degree of radiographic pathosis as long as the tooth remains
asymptomatic.
Doyle et al. published a modification of the rating scale used previously by Casas et al.,
Yacobi et al. and Payne et al. in which 2 disinterested raters classified pulp treated
primary teeth into 1 of 3 outcomes based on radiographic evaluation: N=incisor without
pathologic change; Po=pathologic change present, follow-up recommended; and
Px=pathologic change present, extract.82,83,164,221,317 Primary teeth rated N or Po are
considered acceptable outcomes of vital pulp therapy. Teeth rated as Px are considered
unacceptable outcomes. The original scale published in Casas et al., Yacobi et al. and
Payne et al. included a fourth outcome category H which represented treated teeth with
radiographic changes associated with normal physiologic molar resorption.82,164,221,317
This category was integrated into the N category in Doyle et al.83
Howley et al. published a modification of the radiographic rating scale used by Zurn and
Seale and adapted from Flaitz et al.203,219,319 Two calibrated standardized examiners not
otherwise involved in the study performed the radiographic outcome assessment.
Radiographic outcomes of vital pulp therapy were evaluated and were classified into 1 of
3 outcomes: S=success; Q=questionable, observe; and F=failure, extract. Criteria for S
outcome in pulpotomy treated primary incisors are tapering internal root canal, normal
trabeculation in periapical region and no external pathological changes. Contained
internal resorption and calcific metamorphosis are considered acceptable. Criteria for S
! 73!
outcome in vital treated primary incisors are tapering internal root canal, normal
trabeculation in the periapical region and no external pathological changes. Resorption
of the root canal medicament is considered an acceptable outcome. Criteria for Q
outcome are the presence of questionable periapical radiolucency with trabeculation still
present and/or questionable external root resorption. Criteria for F outcome are
perforating internal resorption, frank radiolucency and/or pathological external root
resorption. Primary teeth rated S are considered acceptable outcomes vital pulp therapy
including pulpotomy and RCT. Teeth rated as Q and F are considered unacceptable
outcomes. The study categorized Q as an unacceptable outcome because the majority of
teeth rated as Q progressed to F during the study period.
The rating scales in Doyle et al. and Howley et al. appear similar as both rate pulp treated
teeth into categorical outcomes. However, the rating scale in Howley et al. defines the
pathological radiographic changes that corresponded to each outcome and provides
specific criteria used to score each primary tooth treated.219 These scoring systems
attempted to quantify and categorize radiographic changes. The raters who performed
the radiographic evaluation in Doyle et al. were not given specific radiographic criteria
for each outcome classification but instead were asked to use their clinical judgment.83
8.1. Concerns regarding outcome assessment in pulp therapy
Concerns have arisen regarding the standardization, validity and reliability of outcome
assessment in pulp therapy studies.320 The efficacy of pulp therapy outcomes has been
measured in various ways. Though clinical and radiographic assessment is the most
! 74!
reported method used to evaluate pulp therapy outcomes, other reported methods have
included histological assessment and survival analysis. In addition to different evaluation
methods used across various pulp therapy outcome studies, these studies have also
assessed outcomes at different times and there has been no consensus regarding the
definition of outcomes.320 An example would be the lack of consensus in criteria
defining acceptable and unacceptable treatment outcomes. Despite many similarities,
most investigators have used their own criteria.
In an attempt to standardize outcome assessment in pulp therapy outcome studies,
Smaı’l-Faugeron et al. developed a standardized core set of clinical and radiographic
component outcomes that could be used to define acceptable and unacceptable outcomes
for all randomized controlled trials assessing pulp therapy outcomes in primary teeth.320
The investigators performed a systematic review of all outcomes used in randomized
controlled trials comparing pulp therapy treatments for primary molars. Using a 3-round
Delphi process, the investigators had expert authors and dentists refine all outcomes
previously reported in the systematic review to what they considered the most relevant
component outcomes. The process identified the following 5 component outcomes that
the investigators suggested should be used to assess acceptable and unacceptable
outcomes of a pulp treatment. The 5 components were soft-tissue pathosis, pain,
pathologic mobility, pathologic radiolucency and pathologic root resorption. This
standardized system would aid in assessing the effectiveness of pulp treatments in
primary teeth across various studies and resolving one of the largest criticisms of pulp
therapy literature. However, it might be an oversimplified outcome rating system that
! 75!
might not take into account all factors clinicians consider when evaluating outcomes.
This standardized outcome assessment might not be a realistic representation of day-to-
day clinical scenarios.
A limitation of these rating scales is that no study has assessed the validity of these
radiographic rating systems. These rating systems have relied heavily on the association
between radiographic signs of pathosis and the histopathological state of infection or
inflammation of the pulp.60,73,74 However, these scales have demonstrated reliability
among evaluators or raters. Reliability has been assessed using inter- and intra-rater
reliability. Kappa scores for inter- and intra-rater reliability have ranged from fair to
excellent/very good based on Cohen’s and Fleiss’ kappa score and the Landis and Koch
interpretation (Table 3).82,83,191,192,203,219,221,317
8.2. Survival analysis
Survival analysis is a statistical technique that deals with the analysis of time duration
from an intervention until an event occurs, such as death in biological organisms or
failure in mechanical systems. Survival analysis is a statistic used by insurance
companies to estimate life expectancy. It has been adopted for clinical trials out of the
concern that clinical and radiographic outcome rating systems are not standardized.
Survival of pulp treated primary teeth can be defined as the probability that the teeth of
interest, at a given time, will still exist after treatment.321 Essentially, it is a prognostic
statistic and predicts the likelihood of the survival of a tooth at various time points in the
future. Using the Kaplan-Meier approach to survival analysis, the exact time of a non-
! 76!
survival event is used to calculate survival probability and can be used to predict survival
until the next event or follow-up interval. Survival curves can be generated for various
treatment groups and predicted survival in each treatment group can be compared using
the Mantel-Cox Log-Rank Test (log-rank test). The Cox proportional hazards model can
generate the hazard or probability of an event at a specific time, given survival of the
tooth up to this time and allows adjustment for any number of covariates, whether they
are discrete or continuous.322
Criteria for survival and non-survival have varied in the literature. In general, treated
teeth that develop clinical or radiographic pathosis are considered to have an
unacceptable treatment outcome. Subjects that drop out or are lost to follow-up are no
longer available for observation and can provide no additional data. These teeth are
considered to be at risk of a non-survival event and considered censored. Censored
observation occurs when the information about the survival time of a treated tooth is
unknown.321
Some investigators have defined non-survival of treated teeth as teeth with unacceptable
clinical or radiographic outcomes, exfoliated and extracted during the follow-up
interval.82,83,191,192 Other investigators defined survival as unacceptable clinical and
radiographic outcome of a treated tooth.85,323
9. Pulp therapy in primary incisors
Currently, there is no consensus with regard to a standard of care for the treatment of
! 77!
carious vital primary incisors with reversible pulpitis. Thirty-eight percent of a randomly
selected sample of AAPD members preferred pulpotomy, 33 percent preferred RCT and
23 percent preferred indirect pulp therapy for treatment of reversibly inflamed primary
incisor pulps.219 Survey respondents were asked to provide the rationale for selection of
their preferred primary incisor pulp technique. Of the 33 percent of survey respondents
who preferred RCT, 56 percent reported that it was the technique taught in the specialty
program from which they had graduated and 33 percent reported their belief that incisor
pulpotomy had poor outcomes.
The vital molar pulpotomy is the technique used by most pediatric dentists, the most
common technique taught in pediatric dentistry residency programs and the accepted
standard of care for carious exposures of asymptomatic vital primary molars in North
America.90,119 The AAPD guideline on pulp therapy states a pulpotomy is indicated
when caries removal results in pulp exposure, however this guideline does not
differentiate between posterior and anterior primary teeth.90 Although the vital pulp
therapy outcomes reported in primary molars cannot be extrapolated to primary incisors,
the anatomy and histology of the pulp in incisors and molars are similar and one would
expect similar outcomes between the two forms of teeth. Little evidence exists to
substantiate that pulpotomy of vital primary incisors have poor outcomes.
Flatiz et al. and Coll et al. were some of the first papers to compare primary incisor pulp
techniques in the 1980s.207,319 Flaitz et al. in a retrospective study compared FC
pulpotomy and ZOE RCT outcomes.319 A total of 144 primary incisors, 57 FC
! 78!
pulpotomy and 87 RCT incisors, were evaluated. The sample included vital and non-
vital incisors as well as incisors treated for caries and trauma. Radiographic evaluation
demonstrated 69 percent of FC pulpotomy and 84 percent of RCT treated incisors were
considered acceptable outcomes. Major weaknesses of the study were the treatment
groups included vital and non-vital incisors and pulpotomy was used to treat non-vital
incisors. Coll et al. in a retrospective study assessed the clinical and radiographic
outcomes of FC pulpotomy, IPT and RCT of carious and traumatized primary incisors.207
Forty-five subjects from a private practice were included in the study. Indications for
pulpotomy treatment were primary incisors with carious or traumatic pulp exposure
presenting with reversible pulpitis. Indications for IPT were similar to that of pulpotomy
except no carious or traumatic pulp exposure was present. Indications for RCT were
based on clinical and radiographic signs of irreversible pulpitis or pulpal necrosis. Total
overall outcome combined clinical and radiographic outcomes. Total acceptable
outcomes reported were 86 percent (24 of 28) for FC pulpotomy, 92 percent (24 of 26)
for IPT and 78 percent (21 of 27) for RCT treated incisors with a mean follow-up
between 42 to 46 months post-treatment. Weaknesses of the study included different
inclusion criteria for each treatment group, a small sample and no comparative statistics
between treatment groups were reported.
Payne et al. in a clinical trial evaluated the clinical and radiographic outcomes of ZOE
RCT in vital primary teeth 24 months post-treatment.317 The sample consisted of healthy
children with primary incisors and/or molars presenting with reversible pulpitis. At 24
months post-treatment, acceptable radiographic outcomes were observed in 83 percent
! 79!
(124 of 150) of RCT treated incisors. Yacobi et al., in a similar study to Payne et al., also
evaluated outcomes of RCT of carious primary incisors and molar with reversible
pulpitis.221 The sample consisted of 106 subjects and acceptable radiographic outcomes
were 76 percent of RCT treated teeth 12 months post-treatment. At 24 months post-
treatment, 59 percent of RCT treated teeth were considered acceptable radiographically.
Primosch et al. in a retrospective study also evaluated the clinical and radiographic
outcomes of RCT with the addition of a 4-minute application of FC prior to obturation.222
Acceptable radiographic outcome of RCT was 81 percent (65 of 80) of treated incisors
after a mean duration of 18 months.
Casas et al. in a randomized controlled trial compared FS pulpotomy and RCT in
cariously exposed vital primary incisors with reversible pulpitis.192 Subjects were
assessed for clinically and radiographically 12- and 24-months post-treatment.
Acceptable clinical outcomes were observed in 78 percent (32 of 41) of FS pulpotomy
and 100 percent (36 of 36) of RCT treated incisors 24 months post-treatment. Acceptable
radiographic outcomes were observed in 42 percent (5 of 12) of FS pulpotomy and 73
percent (8 of 11) of RCT treated incisors. FS pulpotomy and RCT demonstrated no
significant difference in clinical and radiographic outcomes (P<.05). RCT treated
incisors demonstrated significantly higher survival rates than FS pulpotomy treated
incisors 24 months post-treatment (P=.04, log-rank test). One weakness of this study was
the large sample wastage. The final sample size was only 23 incisors with a dropout rate
of over 50 percent.
! 80!
Aminabadi et al. in a randomized controlled trial assessed the clinical and radiographic
outcomes of FC pulpotomy and RCT in primary incisors.324 Teeth were reassessed 12
and 24 months post-operatively. Criteria for acceptable and unacceptable clinical and
radiographic outcomes were not clearly defined. At 24 months post-treatment, 87 percent
(40 of 47) of FC pulpotomy and 96 percent (44 of 45) of RCT treated incisors
demonstrated acceptable clinical outcomes. Clinical outcomes did not differ between FC
pulpotomy and RCT (P>.05). Acceptable radiographic outcomes were shown in 76
percent (35 of 47) of FC pulpotomy and 91 percent (42 of 45) of RCT treated incisors.
RCT had significantly more acceptable radiographic outcomes than FC pulpotomy
(P<.05). Major weaknesses of this study included that the methodology did not define
the parameters for an acceptable clinical and radiographic outcome. The study also used
of a very low concentration of FC (1.5 percent) for FC pulpotomy treatment.
Howley et al. in a split mouth randomized controlled trial compared FC pulpotomy and
Vitapex RCT outcomes in carious vital primary incisors with reversible pulpitis.219
Twenty-nine subjects with 50 matched pairs of incisors were enrolled from a private
pediatric dental office. Subjects were recalled at approximately 6-month intervals with a
follow-up time ranging from 5 to 23 months (mean=13.0+/-5.6 months). At 15 to 23
months post-treatment, 89 percent (29 of 33) of FC pulpotomy and 73 percent (20 of 27)
of Vitapex RCT treated incisors had acceptable radiographic outcomes. FC pulpotomy
and RCT demonstrated equivalent clinical and radiographic outcomes (P>.05).
Three randomized controlled trials on pulp therapy in primary incisors have been
! 81!
published to date. Casas et al. demonstrated RCT incisor survival was significantly
higher than FS pulpotomy incisor survival, however the study suffered from large sample
wastage.192 Two prospective studies have demonstrated conflicting results when
comparing FC pulpotomy and RCT in vital primary incisors. Howley et al. demonstrated
equivalent radiographic outcomes when comparing FC pulpotomy and RCT,219 however,
Aminabadi et al. demonstrated radiographic outcomes of FC pulpotomy were inferior to
RCT.324 These conflicting results may be due to different methodologies. Aminabadi et
al. used a 1.5 percent dilution of FC and a self cure resin with questionable marginal seal
where as Howley used full-strength Buckley’s FC and SSC. Overall, evidence produced
in Howley et al. is representative of a higher quality randomized controlled trial based on
Jadad scoring and Consort guidelines than Aminabadi et al.
Reported clinical outcomes of pulpotomy treated incisors ranged from 78 to 100 and
radiographic outcomes of pulpotomy treated incisors ranged from 59 to 89 percent over
follow-up periods from 12 to 24 months (Appendix 1E). Reported clinical outcomes of
RCT treated incisors ranged from 96 to 100 and radiographic outcomes of RCT treated
incisors ranged from 73 to 91 percent over follow-up periods between 12 to 65 months
(Appendix 1E). The most common radiographic finding noted in pulpotomy treated
incisors was calcific metamorphosis. Based on available evidence, FC pulpotomy and
RCT are effective treatment options for carious vital primary incisors.
Despite a reported anecdotal belief that pulpotomy of vital primary incisors have poor
outcomes there is little evidence-based literature to support this.219 There is currently no
! 82!
strong evidence to support the use of RCT over pulpotomy in carious primary incisors
with reversible pulpitis. Potential benefits of pulpotomy versus RCT include the
pulpotomy is a simpler time efficient technique and more cost effective to the patient.
The Ontario Dental Association Dental Fee Guide of 2013 reports the mean cost of a
primary incisor RCT was twice the cost of a pulpotomy. The reported risk of ectopic
eruption of succedaneous teeth and the retention of RCT obturation materials in the
periodontium risk with primary RCT may not be an issue in pulpotomy treated
incisors.207,214
10. Restoration of primary incisors
Currently, there is a dearth of evidence regarding the restoration of primary teeth that
have undergone pulp therapy, however the restoration of permanent teeth that have
undergone pulp therapy has been assessed. Coronal restorations were demonstrated to
have a significantly greater impact on periapical health than the quality of the RCT in the
permanent dentition.325,326 RCT treated teeth that had amalgam or composite restorations
were 6 times more likely to be lost than crowned permanent teeth.327 A retrospective
study evaluated the outcome of 220 endodontically treated permanent teeth without
crown coverage.328 Overall acceptable outcome rates of RCT treated permanent teeth
were 96 percent at 1-year, 88 percent at 2-years and 36 percent at 5-years. The results of
these studies all substantiate a strong association between coronal restoration and the
survival of RCT teeth in the permanent dentition.327 There is little evidence that has
assessed the effect of restoration type and pulp therapy longevity in the primary dentition.
! 83!
Treatment options for restoring primary incisors with pulp therapy have included: GI
restorations, resin bonded composite restorations, resin bonded composite strip crowns,
SSC, porcelain veneered SSC, resin faced SSC, polycarbonate crowns, polyester crown,
porcelain crowns and zirconium crowns. The longevity of these restorations in a clinical
setting has not been extensively researched. No prospective studies regarding the
restoration of primary incisors has been published, as the majority of studies were
retrospective studies.329 Of 90 papers concerning the restoration of primary anterior teeth
with pre-formed crowns or crown forms, none of the papers were considered strong
clinical evidence based on the Curzon & Toumba scale.329 Reported failure rates of strip
crowns ranged between 0 to 50 percent and pre-veneered metal crowns were 32 to 39
percent in this literature review.329
Composite strip crowns are a common choice for the restoration of primary incisors.
Strip crowns are esthetically pleasing and easily repaired if subsequently chipped or
fractured. However, strip crowns are technique-sensitive as moisture contamination may
compromise esthetics and/or longevity. Adequate tooth structure must be available to
ensure sufficient surface area for bonding and retention. When additional retention is
required in primary incisors due to loss of adequate tooth structure, use of the composite
resin short-post technique (Figure 6) may be considered.330 A case series assessed the
retention rate of the composite resin short-post technique in RCT primary incisors for one
year330. The study followed 92 teeth and observed no loss of retention in any of the
incisors. Four of the 92 teeth were reported to have recurrent decay, 3 crowns were
reported to have incisal fractures and 4 crowns displayed severe attrition.
! 84!
The longevity of resin bonded composite strip crowns placed in primary maxillary
incisors was assessed retrospectively.331 Two hundred children, aged 22 to 48 months,
who had resin strip crowns placed with a follow-up of 24 months were included in the
study. Strip crowns were considered to be acceptable if the surface appeared smooth,
without chipping or caries, the color remained good or acceptable and radiographically,
the margins were properly adapted, without overhangs, and there was no evidence of
pulpal or periapical pathosis. Eighty percent of the restorations were judged to have
acceptable outcomes. The number of carious surfaces of the tooth at baseline influenced
the treatment outcome. Central and lateral incisors with 4 carious surfaces had a higher
strip crown failure rate than strip crowns on 1 or 2 surfaces (P<.001).
The photographic and radiographic outcomes of composite resin strip crowns on non-
pulp treated maxillary primary incisors were assessed in a retrospective study.332 One
hundred forty-five restorations, placed in 52 children, were evaluated after a minimum of
18 months (mean=31 months). The retention rate was 83 percent in strip crowns
followed-up between 18 and 24 months and 78 percent in those followed-up for over 36
months. Ninety-two percent of the teeth demonstrated healthy pulps and 6 percent
demonstrated pulpal changes that did not require immediate treatment. Two percent of
teeth showed radiographic evidence of pulpal pathology requiring non-vital pulp therapy
or extraction. Ninety-nine percent of the strip crowns demonstrated either no gingival
inflammation (43 percent) or mild marginal gingivitis (56 percent).
Parental satisfaction was evaluated and compared with clinical outcomes of bonded resin
! 85!
composite strip crowns in maxillary primary incisors.333 Two pediatric dentists
independently rated clinical outcomes based color photographs of primary maxillary
incisors treated with strip crowns. Parental satisfaction regarding the esthetics of the
crowns was evaluated through a questionnaire. One hundred and twelve restorations,
placed for an average of 18 months (range=6-25 months) were evaluated. Overall
parental satisfaction with the treatment was excellent, however, parental satisfaction with
regard to color was the lowest. No significant differences were found between dentist
and parent evaluations of color, size, and overall appearance (P=.19). Parents rated their
overall satisfaction as being positive regardless of their poor ratings of color, size, or
overall appearance. However, a significant relationship was found between shorter
survival and decreasing overall parental satisfaction (P=.046). Parental satisfaction with
bonded resin composite strip crowns for the treatment of primary incisors with large or
multi-surface caries was excellent however parents’ dissatisfaction was most often related
to color and survival of the restorations.
Esthetics has been a concern of clinicians in pulp treated primary incisors.334 In a
retrospective study, clinical and radiographic outcomes of maxillary incisors restored
with composite resin strips crowns were assessed. Incisors that had pulp treatment were
judged to have far more significant color match discrepancies than those without pulp
treatment.334 MTA, ZOE, Endoflas and iodoform are obturation materials reported to
have the potential to discolor coronal structure in primary teeth.
No prospective trials have been done to assess restorations with pulp therapy in primary
! 86!
incisors. Available evidence reports restoration longevity of resin strip crowns is 50 to
100 percent over a 2 to 3 year follow-up. The resin bonded strip crown is a treatment
modality that appears esthetically pleasing for parents and, for clinicians, provides a
functionally satisfactory means of restoring decayed primary incisors in young children.
Esthetic outcomes of teeth that discolored secondary to pulp therapy were a concern
reported by authors when placing strip crowns.334 Coronal restoration seal may affect
outcomes of pulp therapy. With restoration longevity for resin strip crowns ranging from
50 to 100 percent over a 2 to 3 year follow-up period, longevity of restoration may be a
confounding factor in the assessment of pulp therapy.
11. Summary of literature review
Dental caries is the most common chronic disease in children. Maxillary primary incisors
are one of the most commonly affected teeth in ECC. Caries that extends to the pulps of
primary maxillary incisors is common. The premature loss of primary maxillary incisors
can adversely affect a child’s occlusion, articulation accuracy, esthetics and psychosocial
development. Treatment of these teeth often requires pulp therapy or extraction.
Successful pulp treatment for cariously exposed vital primary incisors avoids premature
tooth loss and maintains incisors in a quiescent state. The choice of pulp therapy and
outcome of treatment is dependent on the pulp status of the tooth. Reversibly inflamed
pulps are candidates for vital pulp therapy. Treatment options of vital pulps with
reversible pulpitis in primary teeth include IPT, pulpotomy, RCT and extraction.
Currently, there is a paucity of dental literature with regards to vital pulp therapy in
! 87!
primary incisors.
Pulp therapy in primary molars has been extensively investigated. The pulpotomy is the
accepted standard of care for carious exposures of vital primary molars with reversible
pulpitis. It is the most widely used and taught vital primary pulp therapy technique in
North America. Variations in the pulpotomy technique include use of FC, FS, NaOCL,
ZOE, electrosurgery, lasers, Ca(OH)2, GA and MTA. Superior radiographic outcomes of
MTA pulpotomy have been demonstrated when compared to FS, FC and Ca(OH)2 in
primary molars.
Only 3 randomized controlled trials have been published to date regarding vital pulp
therapy in primary incisors.192,219,324 Based on the current state of evidence, clinicians
have no guidance with regards to the treatment of vital primary incisors with reversible
pulpitis. No study has been published to date that has assessed the outcomes of MTA
pulpotomies in primary incisors. MTA vital primary incisor pulpotomy could offer a
clinically efficient and cost-effective therapy for vital primary incisors with extensive
caries compared to other therapies such as RCT and FC pulpotomy. Furthermore, using
FS to induce hemostasis after coronal pulp amputation prior to placement of MTA would
improve the clinical efficiency of the pulpotomy procedure.
! 88!
1.12. References
1.! Acs!G,!Shulman!R,!Ng!MW,!Chussid!S.!The!effect!of!dental!rehabilitation!on!the!
body!weight!of!children!with!early!childhood!caries.!Pediatr(Dent.(1999;21(2):109G113.!
2.! Mouradian!WE,!Wehr!E,!Crall!JJ.!Disparities!in!children's!oral!health!and!access!to!dental!care.!JAMA.(2000;284(20):2625G2631.!
3.! Shaw!WC,!Meek!SC,!Jones!DS.!Nicknames,!teasing,!harassment!and!the!salience!of!dental!features!among!school!children.!Br(J(Orthod.(1980;7(2):75G80.!
4.! Riekman!GA,!el!Badrawy!HE.!Effect!of!premature!loss!of!primary!maxillary!incisors!on!speech.!Pediatr(Dent.(1985;7(2):119G122.!
5.! Filstrup!SL,!Briskie!D,!da!Fonseca!M,!Lawrence!L,!Wandera!A,!Inglehart!MR.!Early!childhood!caries!and!quality!of!life:!child!and!parent!perspectives.!Pediatr(Dent.(2003;25(5):431G440.!
6.! Woo!D,!Sheller!B,!Williams!B,!Mancl!L,!Grembowski!D.!Dentists'!and!parents'!perceptions!of!health,!esthetics,!and!treatment!of!maxillary!primary!incisors.!Pediatr(Dent.(2005;27(1):19G23.!
7.! Lamberghini!F,!Kaste!LM,!Fadavi!S,!Koerber!A,!Punwani!IC,!Smith!EB.!An!association!of!premature!loss!of!primary!maxillary!incisors!with!speech!production!of!bilingual!children.!Pediatr(Dent.(2012;34(4):307G311.!
8.! Adewumi!AO,!Horton!C,!Guelmann!M,!DixonGWood!V,!McGorray!SP.!Parental!perception!vs.!professional!assessment!of!speech!changes!following!premature!loss!of!maxillary!primary!incisors.!Pediatr(Dent.(2012;34(4):295G299.!
9.! Nanci!A.!Ten(Cate's(Oral(Histology:(Development,(Structure,(and(Function.!7!ed:!Elsevier!Health!Sciences;!2008.!
10.! Nelson!SJ.!Wheeler's(Dental(Anatomy,(Physiology(and(Occlusion.!Elsevier!Health!Sciences;!2009.!
11.! Barker!BC,!Parsons!KC,!Williams!GL,!Mills!PR.!Anatomy!of!root!canals.!IV!deciduous!teeth.!Aust(Dent(J.(1975;20(2):101G106.!
12.! Murray!PE,!Hafez!AA,!Smith!AJ,!Windsor!LJ,!Cox!CF.!Histomorphometric!analysis!of!odontoblastGlike!cell!numbers!and!dentine!bridge!secretory!activity!following!pulp!exposure.!Int(Endod(J.(2003;36(2):106G116.!
13.! Coppe!C,!Zhang!Y,!Den!Besten!PK.!Characterization!of!primary!dental!pulp!cells!in!vitro.!Pediatr(Dent.(2009;31(7):467G471.!
14.! Miura!M,!Gronthos!S,!Zhao!M,!et!al.!SHED:!stem!cells!from!human!exfoliated!deciduous!teeth.!Proc(Natl(Acad(Sci(U(S(A.(2003;100(10):5807G5812.!
15.! Zhang!JQ,!Nagata!K,!Iijima!T.!Scanning!electron!microscopy!and!immunohistochemical!observations!of!the!vascular!nerve!plexuses!in!the!dental!pulp!of!rat!incisor.!Anat(Rec.(1998;251(2):214G220.!
16.! Matsumoto!M,!Kato!S,!Yokoyama!H,!Ishii!H.![Effect!of!alcohol!on!patients!with!diabetes,!hypertension!or!cardiovascular!disease].!Nihon(Rinsho.(1997;55!Suppl:597G603.!
! 89!
17.! Sawa!Y,!Yoshida!S,!Ashikaga!Y,!Kim!T,!Yamaoka!Y,!Suzuki!M.!Immunohistochemical!demonstration!of!lymphatic!vessels!in!human!dental!pulp.!Tissue(Cell.(1998;30(5):510G516.!
18.! Hargreaves!KM,!Goodis!HE,!Tay!FR.!Seltzer(and(Bender's(Dental(Pulp.!Second!ed:!Quintessence!Pub.;!2012.!
19.! Haug!SR,!Heyeraas!KJ.!Modulation!of!dental!inflammation!by!the!sympathetic!nervous!system.!J(Dent(Res.(2006;85(6):488G495.!
20.! Andrew!D,!Matthews!B.!Properties!of!single!nerve!fibres!that!evoke!blood!flow!changes!in!cat!dental!pulp.!J(Physiol.(2002;542(Pt!3):921G928.!
21.! Fristad!I.!Dental!innervation:!functions!and!plasticity!after!peripheral!injury.!Acta(Odontol(Scand.(1997;55(4):236G254.!
22.! Vongsavan!N,!Matthews!B.!Changes!in!pulpal!blood!flow!and!in!fluid!flow!through!dentine!produced!by!autonomic!and!sensory!nerve!stimulation!in!the!cat.!Proc(Finn(Dent(Soc.(1992;88!Suppl!1:491G497.!
23.! Pohto!P,!Antila!R.!Innervation!of!blood!vessels!in!the!dental!pulp.!Int(Dent(J.(1972;22(2):228G239.!
24.! Olgart!L.!Neural!control!of!pulpal!blood!flow.!Crit(Rev(Oral(Biol(Med.(1996;7(2):159G171.!
25.! Edwall!L,!Kindlova!M.!The!effect!of!sympathetic!nerve!stimulation!on!the!rate!of!disappearance!of!tracers!from!various!oral!tissues.!Acta(Odontol(Scand.(1971;29(4):387G400.!
26.! Heyeraas!KJ,!Kim!S,!Raab!WH,!Byers!MR,!Liu!M.!Effect!of!electrical!tooth!stimulation!on!blood!flow,!interstitial!fluid!pressure!and!substance!P!and!CGRPGimmunoreactive!nerve!fibers!in!the!low!compliant!cat!dental!pulp.!Microvasc(Res.(1994;47(3):329G343.!
27.! Logan!WHG,!Kronfeld!R.!Development!of!the!human!jaws!and!surrounding!structures!from!birth!to!the!age!of!fifteen!years.!J(Am(Dent(Assoc(1933;20(3):379G427.!
28.! Potts!TV,!Cunningham!T,!Finkelstein!MJ,!SilverbergGStrumfeld!L.!The!movement!of!radioactive!molecules!across!dentine!in!vivo!in!the!dog.!Arch(Oral(Biol.(1985;30(4):353G357.!
29.! Pashley!DH,!Matthews!WG.!The!effects!of!outward!forced!convective!flow!on!inward!diffusion!in!human!dentine!in!vitro.!Arch(Oral(Biol.(1993;38(7):577G582.!
30.! Tagami!J,!Hosoda!H,!Burrow!MF,!Nakajima!M.!Effect!of!aging!and!caries!on!dentin!permeability.!Proc(Finn(Dent(Soc.(1992;88!Suppl!1:149G154.!
31.! Rodd!HD,!Boissonade!FM.!Innervation!of!human!tooth!pulp!in!relation!to!caries!and!dentition!type.!J(Dent(Res.(2001;80(1):389G393.!
32.! Rodd!HD,!Boissonade!FM.!Immunocytochemical!investigation!of!neurovascular!relationships!in!human!tooth!pulp.!J(Anat.(2003;202(2):195G203.!
33.! Egan!CA,!Bishop!MA,!Hector!MP.!An!immunohistochemical!study!of!the!pulpal!nerve!supply!in!primary!human!teeth:!evidence!for!the!innervation!of!deciduous!dentine.!J(Anat.(1996;188!(!Pt!3):623G631.!
! 90!
34.! Egan!CA,!Hector!MP,!Bishop!MA.!On!the!pulpal!nerve!supply!in!primary!human!teeth:!evidence!for!the!innervation!of!primary!dentine.!Int(J(Paediatr(Dent.(1999;9(1):57G66.!
35.! Rodd!HD,!Boissonade!FM.!Vascular!status!in!human!primary!and!permanent!teeth!in!health!and!disease.!Eur(J(Oral(Sci.(2005;113(2):128G134.!
36.! Rodd!HD,!Boissonade!FM.!Immunocytochemical!investigation!of!immune!cells!within!human!primary!and!permanent!tooth!pulp.!Int(J(Paediatr(Dent.(2006;16(1):2G9.!
37.! Rapp!R,!Avery!JK,!Strachan!DS.!The!distribution!of!nerves!in!human!primary!teeth.!Anat(Rec.(1967;159(1):89G103.!
38.! Hori!A,!Poureslami!HR,!Parirokh!M,!Mirzazadeh!A,!Abbott!P.!The!ability!of!pulp!sensibility!tests!to!evaluate!the!pulp!status!in!primary!teeth.!Int(J(Paediatr(Dent.(2011;21(6):441G445.!
39.! Petersson!K,!Soderstrom!C,!KianiGAnaraki!M,!Levy!G.!Evaluation!of!the!ability!of!thermal!and!electrical!tests!to!register!pulp!vitality.!Endod(Dent(Traumatol.(1999;15(3):127G131.!
40.! Anand!KJ,!Hickey!PR.!Pain!and!its!effects!in!the!human!neonate!and!fetus.!N(Engl(J(Med.(1987;317(21):1321G1329.!
41.! Fitzgerald!M,!Anand!KJS.!Developmental!neuroanatomy!and!neurophysiology!of!pain.!In:!Schechter!NL,!Berde!CB,!Yaster!M,!eds.!Pain(in(infants,(children(and(adolescents.!Baltimore:!Williams!&!Wilkins;!1993:11G31.!
42.! McGrath!PA.!ChildrenGnot!simply!"little!adults.!In:!Merskey!H,!Loeser!JD,!Dubner!R,!eds.!Paths(of(Pain.!Seattle:!IASP!Press;!2005:433G446.!
43.! Stanford!EA,!Chambers!CT,!Craig!KD.!The!role!of!developmental!factors!in!predicting!young!children's!use!of!a!selfGreport!scale!for!pain.!Pain.(2006;120(1G2):16G23.!
44.! HarokopakisGHajishengallis!E.!Physiologic!root!resorption!in!primary!teeth:!molecular!and!histological!events.!J(Oral(Sci.(2007;49(1):1G12.!
45.! Bolan!M,!Rocha!MJ.!Histopathologic!study!of!physiological!and!pathological!resorptions!in!human!primary!teeth.!Oral(Surg(Oral(Med(Oral(Pathol(Oral(Radiol(Endod.(2007;104(5):680G685.!
46.! Marsh!PD,!Martin!MV,!Lewis!MAO.!Oral(Microbiology.!Elsevier!Science!Health!Science!Division;!2009.!
47.! US!Department!of!Health!and!Human!Services.!Oral!Health!in!America:!A!Report!of!the!Surgeon!GeneralGG!Executive!Summary.!Rockville,!MD:!US!Department!of!Health!and!Human!Services,!National!Institute!of!Dental!and!Craniofacial!Research,!National!Institutes!of!Health;!2000.!
48.! Kim!S,!Liu!M,!Simchon!S,!DorscherGKim!JE.!Effects!of!selected!inflammatory!mediators!on!blood!flow!and!vascular!permeability!in!the!dental!pulp.!Proc(Finn(Dent(Soc.(1992;88!Suppl!1:387G392.!
49.! Heyeraas!KJ,!Kvinnsland!I.!Tissue!pressure!and!blood!flow!in!pulpal!inflammation.!Proc(Finn(Dent(Soc.(1992;88!Suppl!1:393G401.!
50.! Siskin!M.!The(biology(of(the(human(dental(pulp.!Mosby;!1973.!51.! Heyeraas!KJ,!Berggreen!E.!Interstitial!fluid!pressure!in!normal!and!inflamed!
pulp.!Crit(Rev(Oral(Biol(Med.(1999;10(3):328G336.!
! 91!
52.! FerreroGMiliani!L,!Nielsen!OH,!Andersen!PS,!Girardin!SE.!Chronic!inflammation:!importance!of!NOD2!and!NALP3!in!interleukinG1beta!generation.!Clin(Exp(Immunol.(2007;147(2):227G235.!
53.! Maita!E,!Simpson!MD,!Tao!L,!Pashley!DH.!Fluid!and!protein!flux!across!the!pulpodentine!complex!of!the!dog!in!vivo.!Arch(Oral(Biol.(1991;36(2):103G110.!
54.! Vongsavan!N,!Matthews!RW,!Matthews!B.!The!permeability!of!human!dentine!in!vitro!and!in!vivo.!Arch(Oral(Biol.(2000;45(11):931G935.!
55.! Kamal!AM,!Okiji!T,!Kawashima!N,!Suda!H.!Defense!responses!of!dentin/pulp!complex!to!experimentally!induced!caries!in!rat!molars:!an!immunohistochemical!study!on!kinetics!of!pulpal!Ia!antigenGexpressing!cells!and!macrophages.!J(Endod.(1997;23(2):115G120.!
56.! Sakurai!K,!Okiji!T,!Suda!H.!CoGincrease!of!nerve!fibers!and!HLAGDRG!and/or!factorGXIIIaGexpressing!dendritic!cells!in!dentinal!cariesGaffected!regions!of!the!human!dental!pulp:!an!immunohistochemical!study.!J(Dent(Res.(1999;78(10):1596G1608.!
57.! Berggreen!E,!Haug!SR,!Mkonyi!LE,!Bletsa!A.!Characterization!of!the!dental!lymphatic!system!and!identification!of!cells!immunopositive!to!specific!lymphatic!markers.!Eur(J(Oral(Sci.(2009;117(1):34G42.!
58.! Izumi!T,!Kobayashi!I,!Okamura!K,!Sakai!H.!Immunohistochemical!study!on!the!immunocompetent!cells!of!the!pulp!in!human!nonGcarious!and!carious!teeth.!Arch(Oral(Biol.(1995;40(7):609G614.!
59.! Tziafas!D,!Smith!AJ,!Lesot!H.!Designing!new!treatment!strategies!in!vital!pulp!therapy.!J(Dent.(2000;28(2):77G92.!
60.! Koch!G,!Nyborg!H.!Correlation!between!clinical!and!histological!indications!for!pulpotomy!of!deciduous!teeth.!J(Int(Assoc(Dent(Child.(1970;1(1):3G10.!
61.! Rayner!JA,!Southam!JC.!Pulp!changes!in!deciduous!teeth!associated!with!deep!carious!dentine.!J(Dent.(1979;7(1):39G42.!
62.! Trowbridge!HO.!Histology!of!pulpal!inflammation.!In:!Hargreaves!KM,!Goodis!HE,!eds.!Seltzer(and(Bender's(Dental(Pulp.!3rd!ed.!Chicago:!Quintessence!Publishing!Co;!2002:227G246.!
63.! Waterhouse!PJ,!Whitworth!JM,!Camp!JH,!Fuks!AB.!Pediatric!endodontics:!Endodontic!treatment!for!the!primary!and!young!permanent!dentition.!In:!Hargreaves!KM,!Cohen!S,!eds.!Cohen's(Pathways(of(the(Pulp.!St.!Louis:!Mosby;!2011:808G857.!
64.! Bjorndal!L.!The!caries!process!and!its!effect!on!the!pulp:!the!science!is!changing!and!so!is!our!understanding.!Pediatr(Dent.(2008;30(3):192G196.!
65.! Bjorndal!L,!Darvann!T.!A!light!microscopic!study!of!odontoblastic!and!nonGodontoblastic!cells!involved!in!tertiary!dentinogenesis!in!wellGdefined!cavitated!carious!lesions.!Caries(Res.(1999;33(1):50G60.!
66.! Nagaoka!S,!Miyazaki!Y,!Liu!HJ,!Iwamoto!Y,!Kitano!M,!Kawagoe!M.!Bacterial!invasion!into!dentinal!tubules!of!human!vital!and!nonvital!teeth.!J(Endod.(1995;21(2):70G73.!
67.! Merskey!H,!Bogduk!N,!Taxonomy!IAftSoPTFo.!Classification(of(chronic(pain:(descriptions(of(chronic(pain(syndromes(and(definitions(of(pain(terms.!IASP!Press;!1994.!
! 92!
68.! Torneck!CD.!Changes!in!the!fine!structure!of!the!human!dental!pulp!subsequent!to!carious!exposure.!J(Oral(Pathol.(1977;6(2):82G95.!
69.! Clarke!M,!Locker!D,!Berall!G,!Pencharz!P,!Kenny!DJ,!Judd!P.!Malnourishment!in!a!population!of!young!children!with!severe!early!childhood!caries.!Pediatr(Dent.(2006;28(3):254G259.!
70.! Patel!RR,!Tootla!R,!Inglehart!MR.!Does!oral!health!affect!self!perceptions,!parental!ratings!and!videoGbased!assessments!of!children's!smiles?!Community(Dent(Oral(Epidemiol.(2007;35(1):44G52.!
71.! Gable!TO,!Kummer!AW,!Lee!L,!Creaghead!NA,!Moore!LJ.!Premature!loss!of!the!maxillary!primary!incisors:!effect!on!speech!production.!ASDC(J(Dent(Child.(1995;62(3):173G179.!
72.! Glickman!GN.!AAE!Consensus!Conference!on!Diagnostic!Terminology:!background!and!perspectives.!J(Endod.(2009;35(12):1619G1620.!
73.! Waterhouse!PJ,!Nunn!JH,!Whitworth!JM.!Prostaglandin!E2!and!treatment!outcome!in!pulp!therapy!of!primary!molars!with!carious!exposures.!Int(J(Paediatr(Dent.(2002;12(2):116G123.!
74.! Schroder!U.!Agreement!between!clinical!and!histologic!findings!in!chronic!coronal!pulpitis!in!primary!teeth.!Scand(J(Dent(Res.(1977;85(7):583G587.!
75.! Kassa!D,!Day!P,!High!A,!Duggal!M.!Histological!comparison!of!pulpal!inflammation!in!primary!teeth!with!occlusal!or!proximal!caries.!Int(J(Paediatr(Dent.(2009;19(1):26G33.!
76.! Hobson!P.!Pulp!treatment!of!deciduous!teeth.!1.!Factors!affecting!diagnosis!and!treatment.!Br(Dent(J.(1970;128(5):232G238.!
77.! Berman!LH,!Hartwell!GR.!Diagnosis.!10th!ed.!St.!Louis:!Mosby;!2011.!78.! Nooh!AM.!The(Relationship(Between(the(Extent(of(Carious(Involvement(of(the(
Marginal(Ridge(and(Pulpal(Inflammation(in(Primary(Teeth.!UK:!Leeds!Dental!Institute1998.!
79.! Eidelman!E,!Ulmanksy!M,!Michaeli!Y.!Histopathology!of!the!pulp!in!primary!incisors!with!deep!dentinal!caries.!Pediatr(Dent.(1992;14(6):372G375.!
80.! Duggal!MS,!Nooh!A,!High!A.!Response!of!the!primary!pulp!to!inflammation:!a!review!of!the!Leeds!studies!and!challenges!for!the!future.!Eur(J(Paediatr(Dent.(2002;3(3):111G114.!
81.! Guthrie!TJ,!McDonald!RE,!Mitchell!DF.!Dental!Pulp!Hemogram.!J(Dent(Res.(1965;44:678G682.!
82.! Casas!MJ,!Layug!MA,!Kenny!DJ,!Johnston!DH,!Judd!PL.!TwoGyear!outcomes!of!primary!molar!ferric!sulfate!pulpotomy!and!root!canal!therapy.!Pediatr(Dent.(2003;25(2):97G102.!
83.! Doyle!TL,!Casas!MJ,!Kenny!DJ,!Judd!PL.!Mineral!trioxide!aggregate!produces!superior!outcomes!in!vital!primary!molar!pulpotomy.!Pediatr(Dent.(2010;32(1):41G47.!
84.! Peng!L,!Ye!L,!Guo!X,!et!al.!Evaluation!of!formocresol!versus!ferric!sulphate!primary!molar!pulpotomy:!a!systematic!review!and!metaGanalysis.!Int(Endod(J.(2007;40(10):751G757.!
85.! Smith!NL,!Seale!NS,!Nunn!ME.!Ferric!sulfate!pulpotomy!in!primary!molars:!a!retrospective!study.!Pediatr(Dent.(2000;22(3):192G199.!
! 93!
86.! Willard!RM.!Radiographic!changes!following!formocresol!pulpotomy!in!primary!molars.!ASDC(J(Dent(Child.(1976;43(6):414G415.!
87.! Evans!D,!Reid!J,!Strang!R,!Stirrups!D.!A!comparison!of!laser!Doppler!flowmetry!with!other!methods!of!assessing!the!vitality!of!traumatised!anterior!teeth.!Endod(Dent(Traumatol.(1999;15(6):284G290.!
88.! Chen!E,!Abbott!PV.!Evaluation!of!accuracy,!reliability,!and!repeatability!of!five!dental!pulp!tests.!J(Endod.(2011;37(12):1619G1623.!
89.! Asgary!S,!Eghbal!MJ,!Ghoddusi!J.!TwoGyear!results!of!vital!pulp!therapy!in!permanent!molars!with!irreversible!pulpitis:!an!ongoing!multicenter!randomized!clinical!trial.!Clin(Oral(Investig.(2014;18(2):635G641.!
90.! American!Academy!of!Pediatric!Dentistry.!Guideline!on!pulp!therapy!for!primary!and!immature!permanent!teeth:!Reference!Manual!2011G12.!Pediatr(Dent.(2011;33:212G219.!
91.! Wambier!DS,!dos!Santos!FA,!GuedesGPinto!AC,!Jaeger!RG,!Simionato!MR.!Ultrastructural!and!microbiological!analysis!of!the!dentin!layers!affected!by!caries!lesions!in!primary!molars!treated!by!minimal!intervention.!Pediatr(Dent.(2007;29(3):228G234.!
92.! Duque!C,!Negrini!Tde!C,!Sacono!NT,!Spolidorio!DM,!de!Souza!Costa!CA,!Hebling!J.!Clinical!and!microbiological!performance!of!resinGmodified!glassGionomer!liners!after!incomplete!dentine!caries!removal.!Clin(Oral(Investig.(2009;13(4):465G471.!
93.! A!collaborative!effort!of!the!American!Academy!of!Pedodontics!and!the!American!Academy!of!Pediatrics.!Policy!on!early!childhood!caries!(ECC):!classifications.!Reference(Manual(2011R2012.(2011;34(12/13):50G52.!
94.! Lula!EC,!MonteiroGNeto!V,!Alves!CM,!Ribeiro!CC.!Microbiological!analysis!after!complete!or!partial!removal!of!carious!dentin!in!primary!teeth:!a!randomized!clinical!trial.!Caries(Res.(2009;43(5):354G358.!
95.! Paddick!JS,!Brailsford!SR,!Kidd!EA,!Beighton!D.!Phenotypic!and!genotypic!selection!of!microbiota!surviving!under!dental!restorations.!Appl(Environ(Microbiol.(2005;71(5):2467G2472.!
96.! Bjorndal!L,!Larsen!T.!Changes!in!the!cultivable!flora!in!deep!carious!lesions!following!a!stepwise!excavation!procedure.!Caries(Res.(2000;34(6):502G508.!
97.! Magnusson!BO,!Sundell!SO.!Stepwise!excavation!of!deep!carious!lesions!in!primary!molars.!J(Int(Assoc(Dent(Child.(1977;8(2):36G40.!
98.! Maltz!M,!Oliveira!EF,!Fontanella!V,!Carminatti!G.!Deep!caries!lesions!after!incomplete!dentine!caries!removal:!40Gmonth!followGup!study.!Caries(Res.(2007;41(6):493G496.!
99.! Marchi!JJ,!de!Araujo!FB,!Froner!AM,!Straffon!LH,!Nor!JE.!Indirect!pulp!capping!in!the!primary!dentition:!a!4!year!followGup!study.!J(Clin(Pediatr(Dent.(2006;31(2):68G71.!
100.! Casagrande!L,!Falster!CA,!Di!Hipolito!V,!et!al.!Effect!of!adhesive!restorations!over!incomplete!dentin!caries!removal:!5Gyear!followGup!study!in!primary!teeth.!J(Dent(Child.(2009;76(2):117G122.!
101.! Falster!CA,!Araujo!FB,!Straffon!LH,!Nor!JE.!Indirect!pulp!treatment:!in!vivo!outcomes!of!an!adhesive!resin!system!vs!calcium!hydroxide!for!protection!of!the!dentinGpulp!complex.!Pediatr(Dent.(2002;24(3):241G248.!
! 94!
102.! Farooq!NS,!Coll!JA,!Kuwabara!A,!Shelton!P.!Success!rates!of!formocresol!pulpotomy!and!indirect!pulp!therapy!in!the!treatment!of!deep!dentinal!caries!in!primary!teeth.!Pediatr(Dent.(2000;22(4):278G286.!
103.! AlGZayer!MA,!Straffon!LH,!Feigal!RJ,!Welch!KB.!Indirect!pulp!treatment!of!primary!posterior!teeth:!a!retrospective!study.!Pediatr(Dent.(2003;25(1):29G36.!
104.! Bjorndal!L.!Indirect!pulp!therapy!and!stepwise!excavation.!Pediatr(Dent.(2008;30(3):225G229.!
105.! Dunston!B,!Coll!JA.!A!survey!of!primary!tooth!pulp!therapy!as!taught!in!US!dental!schools!and!practiced!by!diplomates!of!the!American!Board!Of!Pediatric!Dentistry.!Pediatr(Dent.(2008;30(1):42G48.!
106.! Vij!R,!Coll!JA,!Shelton!P,!Farooq!NS.!Caries!control!and!other!variables!associated!with!success!of!primary!molar!vital!pulp!therapy.!Pediatr(Dent.(2004;26(3):214G220.!
107.! de!Souza!EM,!Cefaly!DF,!Terada!RS,!Rodrigues!CC,!de!Lima!Navarro!MF.!Clinical!evaluation!of!the!ART!technique!using!high!density!and!resinGmodified!glass!lonomer!cements.!Oral(Health(Prev(Dent.(2003;1(3):201G207.!
108.! Pinto!AS,!de!Araujo!FB,!Franzon!R,!et!al.!Clinical!and!microbiological!effect!of!calcium!hydroxide!protection!in!indirect!pulp!capping!in!primary!teeth.!Am(J(Dent.(2006;19(6):382G386.!
109.! Menezes!JP,!Rosenblatt!A,!Medeiros!E.!Clinical!evaluation!of!atraumatic!restorations!in!primary!molars:!a!comparison!between!2!glass!ionomer!cements.!J(Dent(Child.(2006;73(2):91G97.!
110.! Gruythuysen!RJ,!van!Strijp!AJ,!Wu!MK.!LongGterm!survival!of!indirect!pulp!treatment!performed!in!primary!and!permanent!teeth!with!clinically!diagnosed!deep!carious!lesions.!J(Endod.(2010;36(9):1490G1493.!
111.! Kopel!HM.!The!pulp!capping!procedure!in!primary!teeth!"revisited".!ASDC(J(Dent(Child.(1997;64(5):327G333.!
112.! Fuks!AB.!Pulp!therapy!for!the!primary!and!young!permanent!dentitions.!Dent(Clin(North(Am.(2000;44(3):571G596,!vii.!
113.! Orhan!AI,!Oz!FT,!Orhan!K.!Pulp!exposure!occurrence!and!outcomes!after!1G!or!2Gvisit!indirect!pulp!therapy!vs!complete!caries!removal!in!primary!and!permanent!molars.!Pediatr(Dent.(2010;32(4):347G355.!
114.! Rodd!HD,!Waterhouse!PJ,!Fuks!AB,!Fayle!SA,!Moffat!MA.!Pulp!therapy!for!primary!molars.!Int(J(Paediatr(Dent.(2006;16!Suppl!1:15G23.!
115.! Fuks!AB.!Pulp(therapy(for(the(primary(dentition.!4th!ed.!St.!Louis:!Elsevier!Saunders!Co;!2005.!
116.! Starkey!PE.!Methods!of!preserving!primary!teeth!which!have!exposed!pulps.!ASDC(J(Dent(Child.(1963;30:219G224.!
117.! Aminabadi!NA,!Farahani!RM,!Oskouei!SG.!Formocresol!versus!calcium!hydroxide!direct!pulp!capping!of!human!primary!molars:!two!year!followGup.!J(Clin(Pediatr(Dent.(2010;34(4):317G321.!
118.! Hunter!ML,!Hunter!B.!Vital!pulpotomy!in!the!primary!dentition:!attitudes!and!practices!of!Specialists!in!Paediatric!Dentistry!practising!in!the!United!Kingdom.!Int(J(Paediatr(Dent.(2003;13(4):246G250.!
! 95!
119.! Walker!LA,!Sanders!BJ,!Jones!JE,!et!al.!Current!trends!in!pulp!therapy:!a!survey!analyzing!pulpotomy!techniques!taught!in!pediatric!dental!residency!programs.!J(Dent(Child((Chic).(2013;80(1):31G35.!
120.! Waterhouse!PJ.!"New!age"!pulp!therapy:!personal!thoughts!on!a!hot!debate.!Pediatr(Dent.(2008;30(3):247G252.!
121.! Mejare!I,!Mejare!B.!An!in!vitro!study!with!various!vehicles!of!diffusion!of!formocresol!and!its!components.!Scand(J(Dent(Res.(1978;86(4):259G266.!
122.! Gravenmade!EJ.!Some!biochemical!considerations!of!fixation!in!endodontics.!J(Endod.(1975;1(7):233G237.!
123.! GarciaGGodoy!F.!Penetration!and!pulpal!response!by!two!concentrations!of!formocresol!using!two!methods!of!application.!J(Pedod.(1981;5(2):102G135.!
124.! Kurji!ZA,!Sigal!MJ,!Andrews!P,!Titley!K.!A!retrospective!study!of!a!modified!1Gminute!formocresol!pulpotomy!technique!part!1:!clinical!and!radiographic!findings.!Pediatr(Dent.(2011;33(2):131G138.!
125.! Emmerson!CC,!Miyamoto!O,!Sweet!CA,!Bhatia!HL.!Pulpal!changes!following!formocresol!applications!on!rat!molars!and!human!primary!teeth.!South(California(State(Dental(Association(1959;27(9):309G323.!
126.! Massler!M,!Mansukhani!N.!Effects!of!formocresol!on!the!dental!pulp.!Journal(of(Dentistry(for(Children.(1959;26:277G297.!
127.! Beaver!HA,!Kopel!HM,!Sabes!WR.!The!effect!of!zinc!oxideGeugenol!cement!on!a!formocresolized!pulp.!Journal(of(Dentistry(for(Children.(1966;33:381G396.!
128.! Berger!JE.!Pulp!Tissue!Reaction!to!Formocresol!and!Zinc!OxideGEugenol.!ASDC(J(Dent(Child.(1965;32:13G28.!
129.! Sweet!C.!Treatment!of!vital!exposed!primary!and!young!permanent!teeth.!Journal(of(Dentistry(for(Children.(1956;23(86G89).!
130.! Loos!PJ,!Straffon!LH,!Han!SS.!Biological!effects!of!formocresol.!ASDC(J(Dent(Child.(1973;40(3):193G197.!
131.! Fuks!AB,!Holan!G,!Davis!JM,!Eidelman!E.!Ferric!sulfate!versus!dilute!formocresol!in!pulpotomized!primary!molars:!longGterm!follow!up.!Pediatr(Dent.(1997;19(5):327G330.!
132.! GarciaGGodoy!F,!Novakovic!DP,!Carvajal!IN.!Pulpal!response!to!different!application!times!of!formocresol.!J(Pedod.(1982;6(2):176G193.!
133.! Thompson!KS,!Seale!NS,!Nunn!ME,!Huff!G.!Alternative!method!of!hemorrhage!control!in!full!strength!formocresol!pulpotomy.!Pediatr(Dent.(2001;23(3):217G222.!
134.! Fuks!AB,!Bimstein!E,!Bruchim!A.!Radiographic!and!histologic!evaluation!of!the!effect!of!two!concentrations!of!formocresol!on!pulpotomized!primary!and!young!permanent!teeth!in!monkeys.!Pediatr(Dent.(1983;5(1):9G13.!
135.! Ferreira!DC,!Brito!DG,!Cavalcanti!BN.!Cytokine!production!from!human!primary!teeth!pulp!fibroblasts!stimulated!by!different!pulpotomy!agents.!J(Dent(Child.(2009;76(3):194G198.!
136.! Rolling!I,!Poulsen!S.!Formocresol!pulpotomy!of!primary!teeth!and!occurrence!of!enamel!defects!on!the!permanent!successors.!Acta(Odontol(Scand.(1978;36(4):243G247.!
! 96!
137.! Huth!KC,!HajekGAlGKhatar!N,!Wolf!P,!Ilie!N,!Hickel!R,!Paschos!E.!LongGterm!effectiveness!of!four!pulpotomy!techniques:!3Gyear!randomised!controlled!trial.!Clin(Oral(Investig.(2012;16(4):1243G1250.!
138.! Huth!KC,!Paschos!E,!HajekGAlGKhatar!N,!et!al.!Effectiveness!of!4!pulpotomy!techniquesGGrandomized!controlled!trial.!J(Dent(Res.(2005;84(12):1144G1148.!
139.! Sushynski!JM,!Zealand!CM,!Botero!TM,!et!al.!Comparison!of!gray!mineral!trioxide!aggregate!and!diluted!formocresol!in!pulpotomized!primary!molars:!a!6G!to!24Gmonth!observation.!Pediatr(Dent.(2012;34(5):120G128.!
140.! Zealand!CM,!Briskie!DM,!Botero!TM,!Boynton!JR,!Hu!JC.!Comparing!gray!mineral!trioxide!aggregate!and!diluted!formocresol!in!pulpotomized!human!primary!molars.!Pediatr(Dent.(2010;32(5):393G399.!
141.! Aeinehchi!M,!Dadvand!S,!Fayazi!S,!BayatGMovahed!S.!Randomized!controlled!trial!of!mineral!trioxide!aggregate!and!formocresol!for!pulpotomy!in!primary!molar!teeth.!Int(Endod(J.(2007;40(4):261G267.!
142.! Farsi!N,!Alamoudi!N,!Balto!K,!Mushayt!A.!Success!of!mineral!trioxide!aggregate!in!pulpotomized!primary!molars.!J(Clin(Pediatr(Dent.(2005;29(4):307G311.!
143.! Mettlach!SE,!Zealand!CM,!Botero!TM,!Boynton!JR,!Majewski!RF,!Hu!JC.!Comparison!of!Mineral!Trioxide!Aggregate!and!Diluted!Formocresol!in!Pulpotomized!Human!Primary!Molars:!42Gmonth!FollowGup!and!Survival!Analysis.!Pediatr(Dent.(2013;35(3):87G94.!
144.! Lin!PY,!Chen!HS,!Wang!YH,!Tu!YK.!Primary!molar!pulpotomy:!A!systematic!review!and!network!metaGanalysis.!J(Dent.(2014.!
145.! Shirvani!A,!Asgary!S.!Mineral!trioxide!aggregate!versus!formocresol!pulpotomy:!a!systematic!review!and!metaGanalysis!of!randomized!clinical!trials.!Clin(Oral(Investig.(2014.!
146.! Liteplo!RG,!Beauchamp!R,!Meek!ME,!Chenier!R.!Formaldehyde:(Concise(International(Chemical(Assessment(Document(40.(Geneva2002.!
147.! Health!Canada!I.!Formaldehyde.!Environmental(and(Workplace(Health!2012;!http://www.hcGsc.gc.ca/ewhGsemt/air/in/poll/construction/formaldehydeGeng.php,!2013.!
148.! Berke!JH.!Cytologic!examination!of!the!nasal!mucosa!in!formaldehydeGexposed!workers.!J(Occup(Med.(1987;29(8):681G684.!
149.! Horvath!EP,!Jr.,!Anderson!H,!Jr.,!Pierce!WE,!Hanrahan!L,!Wendlick!JD.!Effects!of!formaldehyde!on!the!mucous!membranes!and!lungs.!A!study!of!an!industrial!population.!JAMA.(1988;259(5):701G707.!
150.! Malaka!T,!Kodama!AM.!Respiratory!health!of!plywood!workers!occupationally!exposed!to!formaldehyde.!Arch(Environ(Health.(1990;45(5):288G294.!
151.! Rølling!I,!Thulin!H.!Allergy!tests!against!formaldehyde,!cresol,!and!eugenol!in!children!with!pulpotomized!primary!teeth.!Scand(J(Dent(Res(1976;84:345G347.!
152.! Longwill!DG,!Marshall!FJ,!Creamer!HR.!Reactivity!of!human!lymphocytes!to!pulp!antigens.!J(Endod.(1982;8(1):27G32.!
153.! Doi!S,!Suzuki!S,!Morishita!M,!et!al.!The!prevalence!of!IgE!sensitization!to!formaldehyde!in!asthmatic!children.!Allergy.(2003;58(7):668G671.!
! 97!
154.! Kerns!WD,!Pavkov!KL,!Donofrio!DJ,!Gralla!EJ,!Swenberg!JA.!Carcinogenicity!of!formaldehyde!in!rats!and!mice!after!longGterm!inhalation!exposure.!Cancer(Res.(1983;43(9):4382G4392.!
155.! Swenberg!JA,!Kerns!WD,!Mitchell!RI,!Gralla!EJ,!Pavkov!KL.!Induction!of!squamous!cell!carcinomas!of!the!rat!nasal!cavity!by!inhalation!exposure!to!formaldehyde!vapor.!Cancer(Res.(1980;40(9):3398G3402.!
156.! Marsh!GM,!Youk!AO,!Buchanich!JM,!Erdal!S,!Esmen!NA.!Work!in!the!metal!industry!and!nasopharyngeal!cancer!mortality!among!formaldehydeGexposed!workers.!Regul(Toxicol(Pharmacol.(2007;48(3):308G319.!
157.! Nilsson!JA,!Zheng!X,!Sundqvist!K,!et!al.!Toxicity!of!formaldehyde!to!human!oral!fibroblasts!and!epithelial!cells:!influences!of!culture!conditions!and!role!of!thiol!status.!J(Dent(Res.(1998;77(11):1896G1903.!
158.! Merk!O,!Speit!G.!Significance!of!formaldehydeGinduced!DNAGprotein!crosslinks!for!mutagenesis.!Environ(Mol(Mutagen.(1998;32(3):260G268.!
159.! Crosby!RM,!Richardson!KK,!Craft!TR,!Benforado!KB,!Liber!HL,!Skopek!TR.!Molecular!analysis!of!formaldehydeGinduced!mutations!in!human!lymphoblasts!and!E.!coli.!Environ(Mol(Mutagen.(1988;12(2):155G166.!
160.! Casas!MJ,!Kenny!DJ,!Judd!PL,!Johnston!DH.!Do!we!still!need!formocresol!in!pediatric!dentistry?!J(Can(Dent(Assoc.(2005;71(10):749G751.!
161.! Zarzar!PA,!Rosenblatt!A,!Takahashi!CS,!Takeuchi!PL,!Costa!Junior!LA.!Formocresol!mutagenicity!following!primary!tooth!pulp!therapy:!an!in!vivo!study.!J(Dent.(2003;31(7):479G485.!
162.! Milnes!AR.!Is!formocresol!obsolete?!A!fresh!look!at!the!evidence!concerning!safety!issues.!Pediatr(Dent.(2008;30(3):237G246.!
163.! Kahl!J,!Easton!J,!Johnson!G,!Zuk!J,!Wilson!S,!Galinkin!J.!Formocresol!blood!levels!in!children!receiving!dental!treatment!under!general!anesthesia.!Pediatr(Dent.(2008;30(5):393G399.!
164.! Formaldehyde.!Industrial(Chemicals!2014;!http://www.carexcanada.ca/en/formaldehyde/.!Accessed!2014/05/20,!2014.!
165.! Centers!for!Disease!Control!and!Prevention.!Formaldehyde.!Documentation(for(Immediately(Dangerous(To(Life(or(Health(Concentrations((IDLHs)!1994,!2013.!
166.! Momeni!S,!Mcbride!JB,!Williams!CH,!Tomlin!N,!Ruby!JD.!2200!Ambient!Formaldehyde!Levels!from!Formocresol!in!a!Dental!Clinic!Environment.!University!of!Alabama!at!Birmingham;!2008.!
167.! Ni!Chaollai!A,!Monteiro!J,!Duggal!MS.!The!teaching!of!management!of!the!pulp!in!primary!molars!in!Europe:!a!preliminary!investigation!in!Ireland!and!the!UK.!Eur(Arch(Paediatr(Dent.(2009;10(2):98G103.!
168.! Jeng!HW,!Feigal!RJ,!Messer!HH.!Comparison!of!the!cytotoxicity!of!formocresol,!formaldehyde,!cresol,!and!glutaraldehyde!using!human!pulp!fibroblast!cultures.!Pediatr(Dent.(1987;9(4):295G300.!
169.! Ranly!DM,!Lazzari!EP.!A!biochemical!study!of!two!bifunctional!reagents!as!alternatives!to!formocresol.!J(Dent(Res.(1983;62(10):1054G1057.!
170.! Ranly!DM.!Glutaraldehyde!purity!and!stability:!implications!for!preparation,!storage,!and!use!as!a!pulpotomy!agent.!Pediatr(Dent.(1984;6(2):83G87.!
! 98!
171.! Ranly!DM,!GarciaGGodoy!F,!Horn!D.!Time,!concentration,!and!pH!parameters!for!the!use!of!glutaraldehyde!as!a!pulpotomy!agent:!an!in!vitro!study.!Pediatr(Dent.(1987;9(3):199G203.!
172.! Tsai!TP,!Su!HL,!Tseng!LH.!Glutaraldehyde!preparations!and!pulpotomy!in!primary!molars.!Oral(Surg(Oral(Med(Oral(Pathol.(1993;76(3):346G350.!
173.! Fuks!AB,!Bimstein!E,!Guelmann!M,!Klein!H.!Assessment!of!a!2!percent!buffered!glutaraldehyde!solution!in!pulpotomized!primary!teeth!of!schoolchildren.!ASDC(J(Dent(Child.(1990;57(5):371G375.!
174.! Civjan!S,!Huget!EF,!Wolfhard!G,!Waddell!LS.!Characterization!of!zinc!oxideGeugenol!cements!reinforced!with!acrylic!resin.!J(Dent(Res.(1972;51(1):107G114.!
175.! Pashley!EL,!Tao!L,!Pashley!DH.!The!sealing!properties!of!temporary!filling!materials.!J(Prosthet(Dent.(1988;60(3):292G297.!
176.! Moller!B,!Schroder!U,!Granath!L.!Effect!of!IRM!on!human!dental!pulp.!Scand(J(Dent(Res.(1983;91(4):281G287.!
177.! Tchaou!WS,!Turng!BF,!Minah!GE,!Coll!JA.!In!vitro!inhibition!of!bacteria!from!root!canals!of!primary!teeth!by!various!dental!materials.!Pediatr(Dent.(1995;17(5):351G355.!
178.! Hume!WR.!Effect!of!eugenol!on!respiration!and!division!in!human!pulp,!mouse!fibroblasts,!and!liver!cells!in!vitro.!J(Dent(Res.(1984;63(11):1262G1265.!
179.! Hume!WR.!In!vitro!studies!on!the!local!pharmacodynamics,!pharmacology!and!toxicology!of!eugenol!and!zinc!oxideGeugenol.!Int(Endod(J.(1988;21(2):130G134.!
180.! Ho!YC,!Huang!FM,!Chang!YC.!Mechanisms!of!cytotoxicity!of!eugenol!in!human!osteoblastic!cells!in!vitro.!Int(Endod(J.(2006;39(5):389G393.!
181.! Hume!WR.!The!pharmacologic!and!toxicological!properties!of!zinc!oxideGeugenol.!J(Am(Dent(Assoc.(1986;113(5):789G791.!
182.! Erdem!AP,!Guven!Y,!Balli!B,!et!al.!Success!rates!of!mineral!trioxide!aggregate,!ferric!sulfate,!and!formocresol!pulpotomies:!a!24Gmonth!study.!Pediatr(Dent.(2011;33(2):165G170.!
183.! Magnusson!B.!Therapeutic!pulpotomy!in!primary!molarsGGclinical!and!histological!followGup.!II.!Zinc!oxideGeugenol!as!wound!dressing.!Odontol(Revy.(1971;22(1):45G54.!
184.! Hansen!HP,!Ravn!JJ,!Ulrich!D.!Vital!pulpotomy!in!primary!molars.!A!clinical!and!histologic!investigation!of!the!effect!of!zinc!oxideGeugenol!cement!and!Ledermix.!Scand(J(Dent(Res.(1971;79(1):13G25.!
185.! Miller!RA,!Bussell!NE,!Ricketts!CK,!Jordi!H.!Analysis!and!purification!of!eugenol.!J(Dent(Res.(1979;58(4):1394G1400.!
186.! Webb!JG,!Jr.,!Bussell!NE.!A!comparison!of!the!inflammatory!response!produced!by!commercial!eugenol!and!purified!eugenol.!J(Dent(Res.(1981;60(9):1724G1728.!
187.! Kim!S,!Kratchman!S.!Modern!endodontic!surgery!concepts!and!practice:!a!review.!J(Endod.(2006;32(7):601G623.!
188.! Fei!AL,!Udin!RD,!Johnson!R.!A!clinical!study!of!ferric!sulfate!as!a!pulpotomy!agent!in!primary!teeth.!Pediatr(Dent.(1991;13(6):327G332.!
! 99!
189.! Lemon!RR,!Steele!PJ,!Jeansonne!BG.!Ferric!sulfate!hemostasis:!effect!on!osseous!wound!healing.!Left!in!situ!for!maximum!exposure.!J(Endod.(1993;19(4):170G173.!
190.! Jeansonne!BG,!Boggs!WS,!Lemon!RR.!Ferric!sulfate!hemostasis:!effect!on!osseous!wound!healing.!II.!With!curettage!and!irrigation.!J(Endod.(1993;19(4):174G176.!
191.! Casas!MJ,!Kenny!DJ,!Johnston!DH,!Judd!PL.!LongGterm!outcomes!of!primary!molar!ferric!sulfate!pulpotomy!and!root!canal!therapy.!Pediatr(Dent.(2004;26(1):44G48.!
192.! Casas!MJ,!Kenny!DJ,!Johnston!DH,!Judd!PL,!Layug!MA.!Outcomes!of!vital!primary!incisor!ferric!sulfate!pulpotomy!and!root!canal!therapy.!J(Can(Dent(Assoc.(2004;70(1):34G38.!
193.! Loh!A,!O'Hoy!P,!Tran!X,!et!al.!EvidenceGbased!assessment:!evaluation!of!the!formocresol!versus!ferric!sulfate!primary!molar!pulpotomy.!Pediatr(Dent.(2004;26(5):401G409.!
194.! Fuks!AB,!Papagiannoulis!L.!Pulpotomy!in!primary!teeth:!review!of!the!literature!according!to!standardized!criteria.!Eur(Arch(Paediatr(Dent.(2006;7(2):64G71;!discussion!72.!
195.! Fernandez!CC,!Martinez!SS,!Jimeno!FG,!Lorente!Rodriguez!AI,!Mercade!M.!Clinical!and!radiographic!outcomes!of!the!use!of!four!dressing!materials!in!pulpotomized!primary!molars:!a!randomized!clinical!trial!with!2Gyear!followGup.!Int(J(Paediatr(Dent.(2012.!
196.! Sonmez!D,!Sari!S,!Cetinbas!T.!A!Comparison!of!four!pulpotomy!techniques!in!primary!molars:!a!longGterm!followGup.!J(Endod.(2008;34(8):950G955.!
197.! Watts!A,!Paterson!RC.!Pulpal!response!to!a!zinc!oxideGeugenol!cement.!Int(Endod(J.(1987;20(2):82G86.!
198.! Holan!G,!Eidelman!E,!Fuks!AB.!LongGterm!evaluation!of!pulpotomy!in!primary!molars!using!mineral!trioxide!aggregate!or!formocresol.!Pediatr(Dent.(2005;27(2):129G136.!
199.! Demir!T,!Cehreli!ZC.!Clinical!and!radiographic!evaluation!of!adhesive!pulp!capping!in!primary!molars!following!hemostasis!with!1.25%!sodium!hypochlorite:!2Gyear!results.!Am(J(Dent.(2007;20(3):182G188.!
200.! Ruby!JD,!Cox!CF,!Mitchell!SC,!Makhija!S,!ChompuGInwai!P,!Jackson!J.!A!randomized!study!of!sodium!hypochlorite!versus!formocresol!pulpotomy!in!primary!molar!teeth.!Int(J(Paediatr(Dent.(2013;23(2):145G152.!
201.! Percinoto!C,!de!Castro!AM,!Pinto!LM.!Clinical!and!radiographic!evaluation!of!pulpotomies!employing!calcium!hydroxide!and!trioxide!mineral!aggregate.!Gen(Dent.(2006;54(4):258G261.!
202.! Shirvani!A,!Hassanizadeh!R,!Asgary!S.!Mineral!Trioxide!Aggregate!vs.!Calcium!Hydroxide!in!Primary!Molar!Pulpotomy:!A!Systematic!Review.!Iran(Endod(J.(2014;9(2):83G88.!
203.! Zurn!D,!Seale!NS.!LightGcured!calcium!hydroxide!vs!formocresol!in!human!primary!molar!pulpotomies:!a!randomized!controlled!trial.!Pediatr(Dent.(2008;30(1):34G41.!
204.! Harrison!JW.!Irrigation!of!the!root!canal!system.!Dent(Clin(North(Am.(1984;28(4):797G808.!
! 100!
205.! GarciaGGodoy!F.!Evaluation!of!an!iodoform!paste!in!root!canal!therapy!for!infected!primary!teeth.!ASDC(J(Dent(Child.(1987;54(1):30G34.!
206.! Holan!G,!Fuks!AB.!A!comparison!of!pulpectomies!using!ZOE!and!KRI!paste!in!primary!molars:!a!retrospective!study.!Pediatr(Dent.(1993;15(6):403G407.!
207.! Coll!JA,!Josell!S,!Nassof!S,!Shelton!P,!Richards!MA.!An!evaluation!of!pulpal!therapy!in!primary!incisors.!Pediatr(Dent.(1988;10(3):178G184.!
208.! Nadkarni!U,!Damle!SG.!Comparative!evaluation!of!calcium!hydroxide!and!zinc!oxide!eugenol!as!root!canal!filling!materials!for!primary!molars:!a!clinical!and!radiographic!study.!J(Indian(Soc(Pedod(Prev(Dent.(2000;18(1):1G10.!
209.! Weiger!R,!Rosendahl!R,!Lost!C.!Influence!of!calcium!hydroxide!intracanal!dressings!on!the!prognosis!of!teeth!with!endodontically!induced!periapical!lesions.!Int(Endod(J.(2000;33(3):219G226.!
210.! Moskovitz!M,!Sammara!E,!Holan!G.!Success!rate!of!root!canal!treatment!in!primary!molars.!J(Dent.(2005;33(1):41G47.!
211.! Ozalp!N,!Saroglu!I,!Sonmez!H.!Evaluation!of!various!root!canal!filling!materials!in!primary!molar!pulpectomies:!an!in!vivo!study.!Am(J(Dent.(2005;18(6):347G350.!
212.! Nakornchai!S,!Banditsing!P,!Visetratana!N.!Clinical!evaluation!of!3Mix!and!Vitapex!as!treatment!options!for!pulpally!involved!primary!molars.!Int(J(Paediatr(Dent.(2010;20(3):214G221.!
213.! Fuks!AB,!Eidelman!E,!Pauker!N.!Root!fillings!with!Endoflas!in!primary!teeth:!a!retrospective!study.!J(Clin(Pediatr(Dent.(2002;27(1):41G45.!
214.! Coll!JA,!Sadrian!R.!Predicting!pulpectomy!success!and!its!relationship!to!exfoliation!and!succedaneous!dentition.!Pediatr(Dent.(1996;18(1):57G63.!
215.! Huang!TH,!Ding!SJ,!Kao!CT.!Biocompatibility!of!various!formula!root!filling!materials!for!primary!teeth.!J(Biomed(Mater(Res(B(Appl(Biomater.(2007;80(2):486G490.!
216.! Mass!E,!Zilberman!UL.!Endodontic!treatment!of!infected!primary!teeth,!using!Maisto's!paste.!ASDC(J(Dent(Child.(1989;56(2):117G120.!
217.! Mortazavi!M,!Mesbahi!M.!Comparison!of!zinc!oxide!and!eugenol,!and!Vitapex!for!root!canal!treatment!of!necrotic!primary!teeth.!Int(J(Paediatr(Dent.(2004;14(6):417G424.!
218.! Spedding!RH.!Incomplete!resorption!of!resorbable!zinc!oxide!root!canal!fillings!in!primary!teeth:!report!of!two!cases.!ASDC(J(Dent(Child.(1985;52(3):214G216.!
219.! Howley!B,!Seale!NS,!McWhorter!AG,!Kerins!C,!Boozer!KB,!Lindsey!D.!Pulpotomy!versus!pulpectomy!for!carious!vital!primary!incisors:!randomized!controlled!trial.!Pediatr(Dent.(2012;34(5):112G119.!
220.! Bawazir!OA,!Salama!FS.!Clinical!evaluation!of!root!canal!obturation!methods!in!primary!teeth.!Pediatr(Dent.(2006;28(1):39G47.!
221.! Yacobi!R,!Kenny!DJ,!Judd!PL,!Johnston!DH.!Evolving!primary!pulp!therapy!techniques.!J(Am(Dent(Assoc.(1991;122(2):83G85.!
222.! Primosch!RE,!Ahmadi!A,!Setzer!B,!Guelmann!M.!A!retrospective!assessment!of!zinc!oxideGeugenol!pulpectomies!in!vital!maxillary!primary!incisors!successfully!restored!with!composite!resin!crowns.!Pediatr(Dent.(2005;27(6):470G477.!
! 101!
223.! Dandashi!MB,!Nazif!MM,!Zullo!T,!Elliott!MA,!Schneider!LG,!Czonstkowsky!M.!An!in!vitro!comparison!of!three!endodontic!techniques!for!primary!incisors.!Pediatr(Dent.(1993;15(4):254G256.!
224.! Nurko!C,!Ranly!DM,!GarciaGGodoy!F,!Lakshmyya!KN.!Resorption!of!a!calcium!hydroxide/iodoform!paste!(Vitapex)!in!root!canal!therapy!for!primary!teeth:!a!case!report.!Pediatr(Dent.(2000;22(6):517G520.!
225.! Sari!S,!Okte!Z.!Success!rate!of!Sealapex!in!root!canal!treatment!for!primary!teeth:!3Gyear!followGup.!Oral(Surg(Oral(Med(Oral(Pathol(Oral(Radiol(Endod.(2008;105(4):e93G96.!
226.! Sigurdsson!A,!Stancill!R,!Madison!S.!Intracanal!placement!of!Ca(OH)2:!a!comparison!of!techniques.!J(Endod.(1992;18(8):367G370.!
227.! Tausche!E,!Luck!O,!Harzer!W.!Prevalence!of!malocclusions!in!the!early!mixed!dentition!and!orthodontic!treatment!need.!Eur(J(Orthod.(2004;26(3):237G244.!
228.! Torabinejad!M,!Hong!CU,!McDonald!F,!Pitt!Ford!TR.!Physical!and!chemical!properties!of!a!new!rootGend!filling!material.!J(Endod.(1995;21(7):349G353.!
229.! Parirokh!M,!Torabinejad!M.!Mineral!trioxide!aggregate:!a!comprehensive!literature!reviewGGPart!I:!chemical,!physical,!and!antibacterial!properties.!J(Endod.(2010;36(1):16G27.!
230.! Tingey!MC,!Bush!P,!Levine!MS.!Analysis!of!mineral!trioxide!aggregate!surface!when!set!in!the!presence!of!fetal!bovine!serum.!J(Endod.(2008;34(1):45G49.!
231.! Nekoofar!MH,!Stone!DF,!Dummer!PM.!The!effect!of!blood!contamination!on!the!compressive!strength!and!surface!microstructure!of!mineral!trioxide!aggregate.!Int(Endod(J.(2010;43(9):782G791.!
232.! Bozeman!TB,!Lemon!RR,!Eleazer!PD.!Elemental!analysis!of!crystal!precipitate!from!gray!and!white!MTA.!J(Endod.(2006;32(5):425G428.!
233.! Sarkar!NK,!Caicedo!R,!Ritwik!P,!Moiseyeva!R,!Kawashima!I.!Physicochemical!basis!of!the!biologic!properties!of!mineral!trioxide!aggregate.!J(Endod.(2005;31(2):97G100.!
234.! Tay!FR,!Pashley!DH,!Rueggeberg!FA,!Loushine!RJ,!Weller!RN.!Calcium!phosphate!phase!transformation!produced!by!the!interaction!of!the!portland!cement!component!of!white!mineral!trioxide!aggregate!with!a!phosphateGcontaining!fluid.!J(Endod.(2007;33(11):1347G1351.!
235.! Saghiri!MA,!Lotfi!M,!Saghiri!AM,!Vosoughhosseini!S,!Aeinehchi!M,!Ranjkesh!B.!Scanning!electron!micrograph!and!surface!hardness!of!mineral!trioxide!aggregate!in!the!presence!of!alkaline!pH.!J(Endod.(2009;35(5):706G710.!
236.! Srinivasan!V,!Patchett!CL,!Waterhouse!PJ.!Is!there!life!after!Buckley's!Formocresol?!Part!I!GG!a!narrative!review!of!alternative!interventions!and!materials.!Int(J(Paediatr(Dent.(2006;16(2):117G127.!
237.! Danesh!G,!Dammaschke!T,!Gerth!HU,!Zandbiglari!T,!Schafer!E.!A!comparative!study!of!selected!properties!of!ProRoot!mineral!trioxide!aggregate!and!two!Portland!cements.!Int(Endod(J.(2006;39(3):213G219.!
238.! Poggio!C,!Lombardini!M,!Alessandro!C,!Simonetta!R.!Solubility!of!rootGendGfilling!materials:!a!comparative!study.!J(Endod.(2007;33(9):1094G1097.!
239.! Shie!MY,!Huang!TH,!Kao!CT,!Huang!CH,!Ding!SJ.!The!effect!of!a!physiologic!solution!pH!on!properties!of!white!mineral!trioxide!aggregate.!J(Endod.(2009;35(1):98G101.!
! 102!
240.! Budig!CG,!Eleazer!PD.!In!vitro!comparison!of!the!setting!of!dry!ProRoot!MTA!by!moisture!absorbed!through!the!root.!J(Endod.(2008;34(6):712G714.!
241.! Chogle!S,!Mickel!AK,!Chan!DM,!Huffaker!K,!Jones!JJ.!Intracanal!assessment!of!mineral!trioxide!aggregate!setting!and!sealing!properties.!Gen(Dent.(2007;55(4):306G311.!
242.! Nekoofar!MH,!Adusei!G,!Sheykhrezae!MS,!Hayes!SJ,!Bryant!ST,!Dummer!PM.!The!effect!of!condensation!pressure!on!selected!physical!properties!of!mineral!trioxide!aggregate.!Int(Endod(J.(2007;40(6):453G461.!
243.! Lee!YL,!Lee!BS,!Lin!FH,!Yun!Lin!A,!Lan!WH,!Lin!CP.!Effects!of!physiological!environments!on!the!hydration!behavior!of!mineral!trioxide!aggregate.!Biomaterials.(2004;25(5):787G793.!
244.! Camilleri!J.!The!chemical!composition!of!mineral!trioxide!aggregate.!J(Conserv(Dent.(2008;11(4):141G143.!
245.! Komabayashi!T,!Spangberg!LS.!Comparative!analysis!of!the!particle!size!and!shape!of!commercially!available!mineral!trioxide!aggregates!and!Portland!cement:!a!study!with!a!flow!particle!image!analyzer.!J(Endod.(2008;34(1):94G98.!
246.! Camilleri!J,!Pitt!Ford!TR.!Mineral!trioxide!aggregate:!a!review!of!the!constituents!and!biological!properties!of!the!material.!Int(Endod(J.(2006;39(10):747G754.!
247.! Fridland!M,!Rosado!R.!MTA!solubility:!a!long!term!study.!J(Endod.(2005;31(5):376G379.!
248.! Torabinejad!M,!Parirokh!M.!Mineral!trioxide!aggregate:!a!comprehensive!literature!reviewGGpart!II:!leakage!and!biocompatibility!investigations.!J(Endod.(2010;36(2):190G202.!
249.! Dreger!LA,!Felippe!WT,!ReyesGCarmona!JF,!Felippe!GS,!Bortoluzzi!EA,!Felippe!MC.!Mineral!trioxide!aggregate!and!Portland!cement!promote!biomineralization!in!vivo.!J(Endod.(2012;38(3):324G329.!
250.! ReyesGCarmona!JF,!Felippe!MS,!Felippe!WT.!The!biomineralization!ability!of!mineral!trioxide!aggregate!and!Portland!cement!on!dentin!enhances!the!pushGout!strength.!J(Endod.(2010;36(2):286G291.!
251.! ReyesGCarmona!JF,!Felippe!MS,!Felippe!WT.!Biomineralization!ability!and!interaction!of!mineral!trioxide!aggregate!and!white!portland!cement!with!dentin!in!a!phosphateGcontaining!fluid.!J(Endod.(2009;35(5):731G736.!
252.! Chang!SW.!Chemical!characteristics!of!mineral!trioxide!aggregate!and!its!hydration!reaction.!Restor(Dent(Endod.(2012;37(4):188G193.!
253.! Chng!HK,!Islam!I,!Yap!AU,!Tong!YW,!Koh!ET.!Properties!of!a!new!rootGend!filling!material.!J(Endod.(2005;31(9):665G668.!
254.! Islam!I,!Chng!HK,!Yap!AU.!XGray!diffraction!analysis!of!mineral!trioxide!aggregate!and!Portland!cement.!Int(Endod(J.(2006;39(3):220G225.!
255.! Torabinejad!M,!Hong!CU,!Pitt!Ford!TR,!Kettering!JD.!Antibacterial!effects!of!some!root!end!filling!materials.!J(Endod.(1995;21(8):403G406.!
256.! Masuda!YM,!Wang!X,!Hossain!M,!et!al.!Evaluation!of!biocompatibility!of!mineral!trioxide!aggregate!with!an!improved!rabbit!ear!chamber.!J(Oral(Rehabil.(2005;32(2):145G150.!
! 103!
257.! Moretton!TR,!Brown!CE,!Jr.,!Legan!JJ,!Kafrawy!AH.!Tissue!reactions!after!subcutaneous!and!intraosseous!implantation!of!mineral!trioxide!aggregate!and!ethoxybenzoic!acid!cement.!J(Biomed(Mater(Res.(2000;52(3):528G533.!
258.! Saidon!J,!He!J,!Zhu!Q,!Safavi!K,!Spangberg!LS.!Cell!and!tissue!reactions!to!mineral!trioxide!aggregate!and!Portland!cement.!Oral(Surg(Oral(Med(Oral(Pathol(Oral(Radiol(Endod.(2003;95(4):483G489.!
259.! Vosoughhosseini!S,!Lotfi!M,!Shahi!S,!et!al.!Influence!of!white!versus!gray!mineral!trioxide!aggregate!on!inflammatory!cells.!J(Endod.(2008;34(6):715G717.!
260.! Martinez!Lalis!R,!Esain!ML,!Kokubu!GA,!Willis!J,!Chaves!C,!Grana!DR.!Rat!subcutaneous!tissue!response!to!modified!Portland!cement,!a!new!mineral!trioxide!aggregate.!Braz(Dent(J.(2009;20(2):112G117.!
261.! Andelin!WE,!Shabahang!S,!Wright!K,!Torabinejad!M.!Identification!of!hard!tissue!after!experimental!pulp!capping!using!dentin!sialoprotein!(DSP)!as!a!marker.!J(Endod.(2003;29(10):646G650.!
262.! Tecles!O,!Laurent!P,!Aubut!V,!About!I.!Human!tooth!culture:!a!study!model!for!reparative!dentinogenesis!and!direct!pulp!capping!materials!biocompatibility.!J(Biomed(Mater(Res(B(Appl(Biomater.(2008;85(1):180G187.!
263.! Takita!T,!Hayashi!M,!Takeichi!O,!et!al.!Effect!of!mineral!trioxide!aggregate!on!proliferation!of!cultured!human!dental!pulp!cells.!Int(Endod(J.(2006;39(5):415G422.!
264.! Kardos!TB,!Hunter!AR,!Hanlin!SM,!Kirk!EE.!Odontoblast!differentiation:!a!response!to!environmental!calcium?!Endod(Dent(Traumatol.(1998;14(3):105G111.!
265.! Okiji!T,!Yoshiba!K.!Reparative!dentinogenesis!induced!by!mineral!trioxide!aggregate:!a!review!from!the!biological!and!physicochemical!points!of!view.!Int(J(Dent.(2009;2009:464280.!
266.! Accorinte!ML,!Loguercio!AD,!Reis!A,!et!al.!Response!of!human!dental!pulp!capped!with!MTA!and!calcium!hydroxide!powder.!Oper(Dent.(2008;33(5):488G495.!
267.! Aeinehchi!M,!Eslami!B,!Ghanbariha!M,!Saffar!AS.!Mineral!trioxide!aggregate!(MTA)!and!calcium!hydroxide!as!pulpGcapping!agents!in!human!teeth:!a!preliminary!report.!Int(Endod(J.(2003;36(3):225G231.!
268.! Bortoluzzi!EA,!Broon!NJ,!Bramante!CM,!et!al.!Mineral!Trioxide!Aggregate!with!or!without!Calcium!Chloride!in!Pulpotomy.!J(Endod.(2008;34(2):172G175.!
269.! Chacko!V,!Kurikose!S.!Human!pulpal!response!to!mineral!trioxide!aggregate!(MTA):!a!histologic!study.!J(Clin(Pediatr(Dent.(2006;30(3):203G209.!
270.! Iwamoto!CE,!Adachi!E,!Pameijer!CH,!Barnes!D,!Romberg!EE,!Jefferies!S.!Clinical!and!histological!evaluation!of!white!ProRoot!MTA!in!direct!pulp!capping.!Am(J(Dent.(2006;19(2):85G90.!
271.! Kuratate!M,!Yoshiba!K,!Shigetani!Y,!Yoshiba!N,!Ohshima!H,!Okiji!T.!Immunohistochemical!analysis!of!nestin,!osteopontin,!and!proliferating!cells!in!the!reparative!process!of!exposed!dental!pulp!capped!with!mineral!trioxide!aggregate.!J(Endod.(2008;34(8):970G974.!
272.! Menezes!R,!Bramante!CM,!Letra!A,!Carvalho!VG,!Garcia!RB.!Histologic!evaluation!of!pulpotomies!in!dog!using!two!types!of!mineral!trioxide!
! 104!
aggregate!and!regular!and!white!Portland!cements!as!wound!dressings.!Oral(Surg(Oral(Med(Oral(Pathol(Oral(Radiol(Endod.(2004;98(3):376G379.!
273.! Nair!PN,!Duncan!HF,!Pitt!Ford!TR,!Luder!HU.!Histological,!ultrastructural!and!quantitative!investigations!on!the!response!of!healthy!human!pulps!to!experimental!capping!with!mineral!trioxide!aggregate:!a!randomized!controlled!trial.!Int(Endod(J.(2008;41(2):128G150.!
274.! Parirokh!M,!Asgary!S,!Eghbal!MJ,!et!al.!A!comparative!study!of!white!and!grey!mineral!trioxide!aggregate!as!pulp!capping!agents!in!dog's!teeth.!Dent(Traumatol.(2005;21(3):150G154.!
275.! Simon!S,!Cooper!P,!Smith!A,!Picard!B,!Ifi!CN,!Berdal!A.!Evaluation!of!a!new!laboratory!model!for!pulp!healing:!preliminary!study.!Int(Endod(J.(2008;41(9):781G790.!
276.! Min!KS,!Park!HJ,!Lee!SK,!et!al.!Effect!of!mineral!trioxide!aggregate!on!dentin!bridge!formation!and!expression!of!dentin!sialoprotein!and!heme!oxygenaseG1!in!human!dental!pulp.!J(Endod.(2008;34(6):666G670.!
277.! Sawicki!L,!Pameijer!CH,!Emerich!K,!AdamowiczGKlepalska!B.!Histological!evaluation!of!mineral!trioxide!aggregate!and!calcium!hydroxide!in!direct!pulp!capping!of!human!immature!permanent!teeth.!Am(J(Dent.(2008;21(4):262G266.!
278.! Yasuda!Y,!Ogawa!M,!Arakawa!T,!Kadowaki!T,!Saito!T.!The!effect!of!mineral!trioxide!aggregate!on!the!mineralization!ability!of!rat!dental!pulp!cells:!an!in!vitro!study.!J(Endod.(2008;34(9):1057G1060.!
279.! Ballal!S,!Venkateshbabu!N,!Nandini!S,!Kandaswamy!D.!An!in!vitro!study!to!assess!the!setting!and!surface!crazing!of!conventional!glass!ionomer!cement!when!layered!over!partially!set!mineral!trioxide!aggregate.!J(Endod.(2008;34(4):478G480.!
280.! Nandini!S,!Ballal!S,!Kandaswamy!D.!Influence!of!glassGionomer!cement!on!the!interface!and!setting!reaction!of!mineral!trioxide!aggregate!when!used!as!a!furcal!repair!material!using!laser!Raman!spectroscopic!analysis.!J(Endod.(2007;33(2):167G172.!
281.! Kayahan!MB,!Nekoofar!MH,!Kazandag!M,!et!al.!Effect!of!acidGetching!procedure!on!selected!physical!properties!of!mineral!trioxide!aggregate.!Int(Endod(J.(2009;42(11):1004G1014.!
282.! Roberts!HW,!Toth!JM,!Berzins!DW,!Charlton!DG.!Mineral!trioxide!aggregate!material!use!in!endodontic!treatment:!a!review!of!the!literature.!Dent(Mater.(2008;24(2):149G164.!
283.! Haglund!R,!He!J,!Jarvis!J,!Safavi!KE,!Spangberg!LS,!Zhu!Q.!Effects!of!rootGend!filling!materials!on!fibroblasts!and!macrophages!in!vitro.!Oral(Surg(Oral(Med(Oral(Pathol(Oral(Radiol(Endod.(2003;95(6):739G745.!
284.! Organization!WH.!Arsenic!Fact(Sheet!2012.!Accessed!March!31,2014,!2014.!285.! Organization!WH.!Exposure!to!arsenic:!a!major!public!health!concern.!
Preventing(disease(through(healthy(environments.(2010.!286.! Flanagan!SV,!Johnston!RB,!Zheng!Y.!Arsenic!in!tube!well!water!in!Bangladesh:!
health!and!economic!impacts!and!implications!for!arsenic!mitigation.!Bull(World(Health(Organ.(2012;90(11):839G846.!
! 105!
287.! Duarte!MA,!De!Oliveira!Demarchi!AC,!Yamashita!JC,!Kuga!MC,!De!Campos!Fraga!S.!Arsenic!release!provided!by!MTA!and!Portland!cement.!Oral(Surg(Oral(Med(Oral(Pathol(Oral(Radiol(Endod.(2005;99(5):648G650.!
288.! Matsunaga!T,!Tsujimoto!M,!Kawashima!T,!et!al.!Analysis!of!arsenic!in!gray!and!white!mineral!trioxide!aggregates!by!using!atomic!absorption!spectrometry.!J(Endod.(2010;36(12):1988G1990.!
289.! Chang!SW,!Baek!SH,!Yang!HC,!et!al.!Heavy!metal!analysis!of!ortho!MTA!and!ProRoot!MTA.!J(Endod.(2011;37(12):1673G1676.!
290.! Chang!SW,!Shon!WJ,!Lee!W,!Kum!KY,!Baek!SH,!Bae!KS.!Analysis!of!heavy!metal!contents!in!gray!and!white!MTA!and!2!kinds!of!Portland!cement:!a!preliminary!study.!Oral(Surg(Oral(Med(Oral(Pathol(Oral(Radiol(Endod.(2010;109(4):642G646.!
291.! Bortoluzzi!EA,!Araujo!GS,!Guerreiro!Tanomaru!JM,!TanomaruGFilho!M.!Marginal!gingiva!discoloration!by!gray!MTA:!a!case!report.!J(Endod.(2007;33(3):325G327.!
292.! Jacobovitz!M,!de!Lima!RK.!Treatment!of!inflammatory!internal!root!resorption!with!mineral!trioxide!aggregate:!a!case!report.!Int(Endod(J.(2008;41(10):905G912.!
293.! Jacobovitz!M,!de!Pontes!Lima!RK.!The!use!of!calcium!hydroxide!and!mineral!trioxide!aggregate!on!apexification!of!a!replanted!tooth:!a!case!report.!Dent(Traumatol.(2009;25(3):e32G36.!
294.! Belobrov!I,!Parashos!P.!Treatment!of!tooth!discoloration!after!the!use!of!white!mineral!trioxide!aggregate.!J(Endod.(2011;37(7):1017G1020.!
295.! Asgary!S,!Parirokh!M,!Eghbal!MJ,!Brink!F.!Chemical!differences!between!white!and!gray!mineral!trioxide!aggregate.!J(Endod.(2005;31(2):101G103.!
296.! Boutsioukis!C,!Noula!G,!Lambrianidis!T.!Ex!vivo!study!of!the!efficiency!of!two!techniques!for!the!removal!of!mineral!trioxide!aggregate!used!as!a!root!canal!filling!material.!J(Endod.(2008;34(10):1239G1242.!
297.! Maroto!M,!Barberia!E,!Planells!P,!Garcia!Godoy!F.!Dentin!bridge!formation!after!mineral!trioxide!aggregate!(MTA)!pulpotomies!in!primary!teeth.!Am(J(Dent.(2005;18(3):151G154.!
298.! Watts!JD,!Holt!DM,!Beeson!TJ,!Kirkpatrick!TC,!Rutledge!RE.!Effects!of!pH!and!mixing!agents!on!the!temporal!setting!of!toothGcolored!and!gray!mineral!trioxide!aggregate.!J(Endod.(2007;33(8):970G973.!
299.! Tsujimoto!M,!Ookubo!A,!Wada!Y,!Matsunaga!T,!Tsujimoto!Y,!Hayashi!Y.!Surface!changes!of!mineral!trioxide!aggregate!after!the!application!of!bleaching!agents:!electron!microscopy!and!an!energyGdispersive!XGray!microanalysis.!J(Endod.(2011;37(2):231G234.!
300.! Felman!D,!Parashos!P.!Coronal!tooth!discoloration!and!white!mineral!trioxide!aggregate.!J(Endod.(2013;39(4):484G487.!
301.! Valles!M,!Mercade!M,!DuranGSindreu!F,!Bourdelande!JL,!Roig!M.!Influence!of!light!and!oxygen!on!the!color!stability!of!five!calcium!silicateGbased!materials.!J(Endod.(2013;39(4):525G528.!
302.! Valles!M,!Mercade!M,!DuranGSindreu!F,!Bourdelande!JL,!Roig!M.!Color!stability!of!white!mineral!trioxide!aggregate.!Clin(Oral(Investig.(2013;17(4):1155G1159.!
! 106!
303.! Sanz!O,!HaroGPoniatowski!E,!Gonzalo!J,!Navarro!JF.!Influence!of!the!melting!conditions!of!heavy!metal!oxide!glasses!containing!bismuth!oxide!on!their!optical!absorption.!Journal(of(nonRcrystalline(solids.(2006;352:761G768.!
304.! Zhang!Y,!Yang!Y,!Zheng!J,!Hua!W,!Chen!G.!Effects!of!oxidizing!additives!on!optical!properties!of!Bi2O3GB2O3GSiO2!glasses.!Journal(of(the(American(Ceramic(Society.(2008;91(10):3410G3412.!
305.! Zhang!L,!Wang!W,!Yang!J,!Chen!Z,!Zhang!W,!Liu!S.!Sonochemical!synthesis!of!nanocrystallite!Bi2O3!as!a!visibleGlightGdriven!photocatalyst.!Applied(catalysis(A(Geneneral.(2006;308:105G110.!
306.! Turro!NJ.!Modern(Molecular(Photochemistry.!University!Science!Books;!1991.!307.! Anthonappa!RP,!King!NM,!Martens!LC.!Is!there!sufficient!evidence!to!support!
the!longGterm!efficacy!of!mineral!trioxide!aggregate!(MTA)!for!endodontic!therapy!in!primary!teeth?!Int(Endod(J.(2013;46(3):198G204.!
308.! Asgary!S,!Shirvani!A.!Comment!on!methodological!problems!of!'Is!there!sufficient!evidence!to!support!the!longGterm!efficacy!of!mineral!trioxide!aggregate!for!endodontic!therapy!in!primary!teeth?'!by!Anthonappa!RP!et!al.!(International!Endodontic!Journal,!46,!198G204,!2013).!Int(Endod(J.(2013.!
309.! Curzon!ME,!Toumba!KJ.!Restoration!of!primary!teeth:!clinical!criteria!for!assessment!of!the!literature.!Eur(Arch(Paediatr(Dent.(2006;7(2):48G52.!
310.! Oliveira!TM,!Moretti!AB,!Sakai!VT,!et!al.!Clinical,!radiographic!and!histologic!analysis!of!the!effects!of!pulp!capping!materials!used!in!pulpotomies!of!human!primary!teeth.!Eur(Arch(Paediatr(Dent.(2013;14(2):65G71.!
311.! Bortoluzzi!EA,!Broon!NJ,!Bramante!CM,!Felippe!WT,!Tanomaru!Filho!M,!Esberard!RM.!The!influence!of!calcium!chloride!on!the!setting!time,!solubility,!disintegration,!and!pH!of!mineral!trioxide!aggregate!and!white!Portland!cement!with!a!radiopacifier.!J(Endod.(2009;35(4):550G554.!
312.! Monteiro!Bramante!C,!Demarchi!AC,!de!Moraes!IG,!et!al.!Presence!of!arsenic!in!different!types!of!MTA!and!white!and!gray!Portland!cement.!Oral(Surg(Oral(Med(Oral(Pathol(Oral(Radiol(Endod.(2008;106(6):909G913.!
313.! Vivan!RR,!OrdinolaGZapata!R,!Bramante!CM,!et!al.!Evaluation!of!the!radiopacity!of!some!commercial!and!experimental!rootGend!filling!materials.!Oral(Surg(Oral(Med(Oral(Pathol(Oral(Radiol(Endod.(2009;108(6):e35G38.!
314.! Primus!CM.!Comments!on!"arsenic!release!provided!by!MTA!and!Portland!cement"!by!Duarte!MA,!et!al.!Oral(Surg(Oral(Med(Oral(Pathol(Oral(Radiol(Endod.(2006;101(4):416G417;!author!reply!417G418.!
315.! Dean!JA,!Mack!RB,!Fulkerson!BT,!Sanders!BJ.!Comparison!of!electrosurgical!and!formocresol!pulpotomy!procedures!in!children.!Int(J(Paediatr(Dent.(2002;12(3):177G182.!
316.! Hicks!MJ,!Barr!ES,!Flaitz!CM.!Formocresol!pulpotomies!in!primary!molars:!a!radiographic!study!in!a!pediatric!dentistry!practice.!J(Pedod.(1986;10(4):331G339.!
317.! Payne!RG,!Kenny!DJ,!Johnston!DH,!Judd!PL.!TwoGyear!outcome!study!of!zinc!oxideGeugenol!root!canal!treatment!for!vital!primary!teeth.!J(Can(Dent(Assoc.(1993;59(6):528G530,!533G526.!
! 107!
318.! Strange!DM,!Seale!NS,!Nunn!ME,!Strange!M.!Outcome!of!formocresol/ZOE!subGbase!pulpotomies!utilizing!alternative!radiographic!success!criteria.!Pediatr(Dent.(2001;23(4):331G336.!
319.! Flaitz!CM,!Barr!ES,!Hicks!MJ.!Radiographic!evaluation!of!pulpal!therapy!for!primary!anterior!teeth.!ASDC(J(Dent(Child.(1989;56(3):182G185.!
320.! Smaı%̈lGFaugeron!V,!Chabouis!HF,!Durieux!P,!Attal!JP,!MullerGBolla!M,!Courson!F.!Development!of!a!core!set!of!outcomes!for!randomized!controlled!trials!with!multiple!outcomes!–!example!of!pulp!treatments!of!primary!teeth!for!extensive!decay!in!children.!PLoS(ONE.(2013;8(1):e51908.!
321.! Rosner!BA.!Fundamentals(of(Biostatistics.!ThomsonGBrooks/Cole;!2006.!322.! Norman!GR,!Streiner!DL.!Biostatistics:(The(Bare(Essentials.!B.C.!Decker;!2008.!323.! Markovic!D,!Zivojinovic!V,!Vucetic!M.!Evaluation!of!three!pulpotomy!
medicaments!in!primary!teeth.!Eur(J(Paediatr(Dent.(2005;6(3):133G138.!324.! Aminabadi!NA,!Farahani!RM,!Gajan!EB.!A!clinical!study!of!formocresol!
pulpotomy!versus!root!canal!therapy!of!vital!primary!incisors.!J(Clin(Pediatr(Dent.(2008;32(3):211G214.!
325.! Ray!HA,!Trope!M.!Periapical!status!of!endodontically!treated!teeth!in!relation!to!the!technical!quality!of!the!root!filling!and!the!coronal!restoration.!Int(Endod(J.(1995;28(1):12G18.!
326.! Kirkevang!LL,!Orstavik!D,!HorstedGBindslev!P,!Wenzel!A.!Periapical!status!and!quality!of!root!fillings!and!coronal!restorations!in!a!Danish!population.!Int(Endod(J.(2000;33(6):509G515.!
327.! Aquilino!SA,!Caplan!DJ.!Relationship!between!crown!placement!and!the!survival!of!endodontically!treated!teeth.!J(Prosthet(Dent.(2002;87(3):256G263.!
328.! Nagasiri!R,!Chitmongkolsuk!S.!LongGterm!survival!of!endodontically!treated!molars!without!crown!coverage:!a!retrospective!cohort!study.!J(Prosthet(Dent.(2005;93(2):164G170.!
329.! Waggoner!WF.!Anterior!crowns!for!primary!anterior!teeth:!an!evidence!based!assessment!of!the!literature.!Eur(Arch(Paediatr(Dent.(2006;7(2):53G57;!discussion!57.!
330.! Judd!PL,!Kenny!DJ,!Johnston!DH,!Yacobi!R.!Composite!resin!shortGpost!technique!for!primary!anterior!teeth.!The(journal(of(the(American(Dental(Association.(1990;120(5):553G555.!
331.! Ram!D,!Fuks!AB.!Clinical!performance!of!resinGbonded!composite!strip!crowns!in!primary!incisors:!a!retrospective!study.!Int(J(Paediatr(Dent.(2006;16(1):49G54.!
332.! Kupietzky!A,!Waggoner!WF.!Parental!satisfaction!with!bonded!resin!composite!strip!crowns!for!primary!incisors.!Pediatr(Dent.(2004;26(4):337G340.!
333.! Kupietzky!A,!Waggoner!WE,!Galea!J.!LongGterm!photographic!and!radiographic!assessment!of!bonded!resin!composite!strip!crowns!for!primary!incisors:!results!after!3!years.!Pediatr(Dent.(2005;27(3):221G225.!
334.! Kupietzky!A,!Waggoner!WF,!Galea!J.!The!clinical!and!radiographic!success!of!bonded!resin!composite!strip!crowns!for!primary!incisors.!Pediatr(Dent.(2003;25(6):577G581.!
! 108!
335.! Godhi!B,!Sood!PB,!Sharma!A.!Effects!of!mineral!trioxide!aggregate!and!formocresol!on!vital!pulp!after!pulpotomy!of!primary!molars:!An!in!vivo!study.!Contemp(Clin(Dent.(2011;2(4):296G301.!
336.! Ansari!G,!Ranjpour!M.!Mineral!trioxide!aggregate!and!formocresol!pulpotomy!of!primary!teeth:!a!2Gyear!followGup.!Int(Endod(J.(2010;43(5):413G418.!
337.! SimancasGPallares!MA,!DiazGCaballero!AJ,!LunaGRicardo!LM.!Mineral!trioxide!aggregate!in!primary!teeth!pulpotomy.!A!systematic!literature!review.!Med(Oral(Patol(Oral(Cir(Bucal.(2010;15(6):e942G946.!
338.! Subramaniam!P,!Konde!S,!Mathew!S,!Sugnani!S.!Mineral!trioxide!aggregate!as!pulp!capping!agent!for!primary!teeth!pulpotomy:!2!year!follow!up!study.!J(Clin(Pediatr(Dent.(2009;33(4):311G314.!
339.! Bahrololoomi!Z,!Moeintaghavi!A,!Emtiazi!M,!Hosseini!G.!Clinical!and!radiographic!comparison!of!primary!molars!after!formocresol!and!electrosurgical!pulpotomy:!a!randomized!clinical!trial.!Indian(J(Dent(Res.(2008;19(3):219G223.!
340.! Ng!FK,!Messer!LB.!Mineral!trioxide!aggregate!as!a!pulpotomy!medicament:!an!evidenceGbased!assessment.!Eur(Arch(Paediatr(Dent.(2008;9(2):58G73.!
341.! Noorollahian!H.!Comparison!of!mineral!trioxide!aggregate!and!formocresol!as!pulp!medicaments!for!pulpotomies!in!primary!molars.!Br(Dent(J.(2008;204(11):E20.!
342.! Peng!L,!Ye!L,!Tan!H,!Zhou!X.!Evaluation!of!the!formocresol!versus!mineral!trioxide!aggregate!primary!molar!pulpotomy:!a!metaGanalysis.!Oral(Surg(Oral(Med(Oral(Pathol(Oral(Radiol(Endod.(2006;102(6):e40G44.!
343.! Saltzman!B,!Sigal!M,!Clokie!C,!Rukavina!J,!Titley!K,!Kulkarni!GV.!Assessment!of!a!novel!alternative!to!conventional!formocresolGzinc!oxide!eugenol!pulpotomy!for!the!treatment!of!pulpally!involved!human!primary!teeth:!diode!laserGmineral!trioxide!aggregate!pulpotomy.!Int(J(Paediatr(Dent.(2005;15(6):437G447.!
344.! Agamy!HA,!Bakry!NS,!Mounir!MM,!Avery!DR.!Comparison!of!mineral!trioxide!aggregate!and!formocresol!as!pulpGcapping!agents!in!pulpotomized!primary!teeth.!Pediatr(Dent.(2004;26(4):302G309.!
345.! Ibricevic!H,!AlGJame!Q.!Ferric!sulphate!and!formocresol!in!pulpotomy!of!primary!molars:!long!term!followGup!study.!Eur(J(Paediatr(Dent.(2003;4(1):28G32.!
346.! Ibricevic!H,!alGJame!Q.!Ferric!sulfate!as!pulpotomy!agent!in!primary!teeth:!twenty!month!clinical!followGup.!J(Clin(Pediatr(Dent.(2000;24(4):269G272.!
!
! 109!
1.13. Tables & Figures
Table 1. Sensitivity and specificity of sensibility test in the primary (Hori et al. 2011) and permanent dentition (Petersson et al. 1999)
Cold Test Hot Test Electric Pulp Test Sensitivity Specificity Sensitivity Specificity Sensitivity Specificity Permanent Dentition 0.83 0.93 0.86 0.41 0.72 0.93
Primary Dentition 0.73 0.75 0.87 0.71 0.90 0.95 !(
!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!
! 110!
Table(2.(Commercially(available(forms(of(mineral(trioxide(aggregate((MTA)312(
Materials Distributor Production Site ProRoot MTA Dentsply Tulsa Dental Tulsa, Oklahoma, USA Tooth-Colored MTA Dentsply Tulsa Dental Tulsa, Oklahoma, USA Gray MTA Angelus Angelus Indústria de Produtos
Odontológicos Ltda. Londrina, PR, Brazil
White MTA Angelus Angelus Indústria de Produtos Odontológicos Ltda.
Londrina, PR, Brazil
Angelus MTA-Obtura Angelus Indústria de Produtos Odontológicos Ltda.
Londrina, PR, Brazil
Egeo CPM in white Egeo S.R.L. Buenos Aires, Argentina Egeo CPM sealer Egeo S.R.L. Buenos Aires, Argentina MTA Bio Angelus Indústria de Produtos
Odontológicos Ltda. Londrina, PR, Brazil
(
(
(
(
(
(
(
(
(
(
!!!!!!!!!!!!!
! 111!
Table(3.(Intra9(and(inter9rater(Kappa(scores(of(studies(using(radiographic(classification(systems(in(primary(teeth(
Study Kappa Score Interpretation
Method
Intra-rater Reliability
Intra-rater Reliability
Interpretation
Inter-rater Reliability
Inter-rater Reliability
Interpretation Mettlach et al.
2013 Cohen’s N/A N/A 0.49-0.57 Moderate
Howley et al. 2012
Cohen’s 1 Very good 0.77 Good
Doyle et al. 2010
Cohen’s 0.68 Good 0.58 Moderate
Zurn and Seale 2008
Cohen’s N/A N/A 0.80 Very good
Casas et al. 2004b
Fleiss’ 0.71 Good 0.75 Good
Casas et al. 2004a
Fleiss’ 0.61 Good 0.54 Fair
Casas et al. 2003
Fleiss’ 0.71 Good 0.75 Good
Payne et al. 1993
Fleiss’ 0.84 Very good 0.58 Fair
Yacobi et al. 1991
Fleiss’ N/A N/A 0.41-0.56 Fair
(
! 112!
Figure(1.!Schematic!representation!of!dentin,!predentin,!odontoblasts!layer,!cellGfree!zone!and!cellGrich!zone!within!the!pulp.!!Adapted!from!Nanci!2008.
! 113!
!
Figure(2.!Schematic!diagram!of!the!!various!types!of!dentin!and!!their!disG!tribution!within!a!tooth.!!Attrition!(blue!!arrow),!abrasion!(toothbrush)!and!cavG!itation!secondary!to!caries!are!shown!!to!stimulate!tertiary!dentin.!!Adapted!!from!Nanci!2008.!
! 114!
Figure(3.(Histological!section!of!dentin.!!The!black!arrows!depict!!a!region!where!dentinal!tubules!change!orientation!delineating!!the!junction!between!primary!and!secondary!dentin.!!Adapted!!from!Nanci!2008.!
! 115!
Figure(4.((A)(Discolouration(of(Tooth9coloured(MTA(noted(after(3(days.((Note(whiter(end((top)(was(open(to(PBS(solution.((B)(Tooth9coloured(MTA(sample(after(3(day9set(in(mold(followed(by(1(week(of(air(exposure.(
! 116!
Figure(5.(Spectrophotometric(images(of(samples(of(Tooth9colored(ProRoot(MTA(irradiated(with(various(light(sources(taken(at(different(time(points.(
! 117!
Figure(6.(Composite(resin(short9post(technique.(((
Adapted(from(Judd(et(al.(1990.
! 118!
1.14. Appendix
1.14.1. Summary of published vital pulp therapy investigations (
Appendix(1A.(Summary(of(published(formocresol(pulpotomy(clinical(controlled(trials,(meta9analysis(and(systematic(reviews.(Formocresol,(FC;(mineral(trioxide(aggregate,(MTA;(calcium(hydroxide,(Ca(OH)2;(ferric(sulphate,(FS;(root(canal(therapy,(RCT;(sodium(hypochlorite,((NaOCl);(=,(not(significantly(different(than;(>,(significantly(higher(acceptable(outcome(rates(than;(<,(significantly(lower(outcomes(rates(than.(
Investigators& *Level&of&Evidence&
Follow9up&&
(months)&
Statistical&Analysis&
FC&Acceptable&Outcomes&(%)&
Statistical&Outcomes&
Lin&et&al.&2014144&
Ia# 18&24# Odds#ratio# Meta&analysis#and#
systematic#review#
FC#<#MTA#(P<.05)#for#radiographic#outcome##
FC#>#Ca(OH)2#(P<.05)#for#clinical#outcome##
FC#>#Ca(OH)2#(P<.05)#for#radiographic#outcome##
FC#>#laser#(P<.05)#for#clinical#outcome##
FC#>#laser#(P<.05)#for#radiographic#outcome##
Shirvani&et&al.&2014145&
Ia# 6&24# Relative#
risk#
Meta&analysis# FC#3.85#at#6#months,#2.70#at#12#months#and#2.44#
at#24#months#the#relative#risk#for#an#unacceptable#
outcome#compared#to#MTA#
#
Mettlach&et&al.&2013143&
Ib# 6&42# Percent#
acceptable#
outcomes#
#
Survival#
#
Odds#ratio#
Clinical#=#99##
Radiographic#=#79#
Survival#clinical#=#.95#
Survival#
radiographic#=#.47#
MTA#>#FC#(P&<.001)#for#radiographic#outcome##
MTA#>#FC#(P<.001)#for#radiographic#survival##
Ruby&et&al.&2013200&
Ib# 12# Percent#
acceptable#
outcome#
Clinical#=#100#
Radiographic#=#90#
FC#=#NaOCl#(P>.05)#for#clinical#and#radiographic#outcomes#
Howley&et&al.&2012219&
Ib# 15&23# Percent#
acceptable#
outcome#
Clinical#=#100#
Radiographic#=#89#
FC#=#RCT#(P>.05)#for#clinical#and#radiographic#outcomes#
Sushynski&et&al.&2012139&&
Ib# 24# Percent#
acceptable#
outcome#
Clinical#=#98#
Radiographic#=#85#
MTA#>#FC#(P<.05)#for#radiographic#outcome#
Huth&et&al.&2012137&
Ib# 36# Percent#
acceptable#
outcome#
Total#(clinical#and#
radiographic)#=#72#
#
FC#=#Er:YAG#=#Ca(OH)2#=#FS##(P>.05)#for#total#(clinical#and#radiographic)#outcome#
#
Fernandez&et&al.&2012195&
Ib# 24# Percent#
acceptable#
outcome#
Radiographic#=#95# FC#=#FS#=#MTA#=#NaOCl#(P>.05)#for#clinical#and#radiographic#outcomes#
Godhi&et&al.&2011335
#
IIb# 12# Percent#
acceptable#
outcome#
Radiographic#=#88# FC#=#MTA#(P>.05)#for#clinical#and#radiographic#outcomes#
Erdem&et&al.&2011182&
Ib# 24# Percent#
acceptable#
outcome#
Total#(clinical#and#
radiographic)#=#96#
FC#=#MTA#=#FS#(P>.05)#for#clinical#and#radiographic#outcomes#
Ansari&and&Ranjpour&2010336&"
Ib# 24# Percent#
acceptable#
outcome#
Radiographic#=#90# FC#=#MTA#(P>.05)#for#clinical#and#radiographic#outcomes#
Simancas9Pallares&et&al.2010337&
Ia# 6#to#<#74# # Systematic#review# MTA#>#FC#for#clinical#and#radiographic#outcomes#
Zealand&et&al.&2010140&#
Ib# 6# Percent#
acceptable#
outcome#
Clinical#=#97#
Radiographic#=#86#
MTA#>#FC#(P<.05)#for#radiographic#outcome#
Subramanian&et&al.2009338&
Ib# 24# Percent#
acceptable#
Clinical#=#100##
Radiographic#=#85#
FC#=#MTA#(P<.05)#for#clinical#and#radiographic#outcomes#
! 119!
outcome#
Aminabadi&et&al.&2008324&
Ib# 24# Percent#
acceptable#
outcome#
Clinical#=#87#
Radiographic#=#76#
RCT#>#FC#(P<.05)#for#radiographic#outcomes#
Bahrololoomi&et&al.&2008339&
Ib# 9# Percent#
acceptable#
outcome#
Clinical#=#100#
Radiographic#=#97#
FC#=#ES#(P>.05)#for#clinical#and#radiographic#outcomes#
Ng&and&Messer&2008340&
Ia# 4&91# Percent#
acceptable#
outcome#
Meta&analysis#
#
MTA#>#FC#(P<.05)#for#clinical#and#radiographic#outcomes#
Noorollahian&2008341&
Ib# 24# Percent#
acceptable#
outcome#
Clinical#=#100#
Radiographic#=#100#
MTA#=#FC#(P>0.05)#for#clinical#and#radiographic#outcomes#
Sonmez&et&al.&2008196&
Ib# 24# Percent#
acceptable#
outcome#
Radiographic#=#77# FC#=#FS#=#Ca(OH)2#=#MTA#(P>.05)#for#clinical#and#radiographic#outcomes#
Zurn&and&Seale&2008203&
Ib# 13# Percent#
acceptable#
outcome#
Clinical#=#97#
Radiographic#=#97#
#
FC#>#Ca(OH)2#(P>.05)#for#clinical#and#radiographic#outcomes#
Aeinehchi&et&al.2007141&
Ib# 6# Percent#
acceptable#
outcome#
Clinical#=#100#
Radiographic#=#89#
#
MTA#>#FC#(P<.05)#for#radiographic#outcomes#
Peng&et&al.&200784&
IIa# >#6# Percent#
acceptable#
outcome#
Meta&analysis## FC#=#FS#(P>.05)#for#clinical#and#radiographic#outcomes#
Peng&et&al.&2006342&
IIa# 1&74# Percent#
acceptable#
outcome#
Meta&analysis# MTA#>#FC#(P<.05)#for#radiographic#outcomes#
Holan&et&al.&2005198&#
Ib# 4#to#74#
(mean=3
8)#
Percent#
acceptable#
outcome#
Radiographic#=#83# FC#=#MTA#(P>.05)#for#radiographic#outcomes#
Huth&et&al.&2005138&#
Ib# 24# Percent#
acceptable#
outcome#
Total#(clinical#and#
radiographic)#=#85#
FC#>#Ca(OH)2#(P=.001)#for#total#(clinical#and#radiographic)#outcome#
FC#=#Er:YAG#=#FS#(P>.05)#for#total#(clinical#and#radiographic)#outcome#
Saltzman&et&al.&2005343&
Ib# 3&15# Percent#
acceptable#
outcome#
Clinical#=#100#
Radiographic#=#88#
FC#=#Laser+MTA#(P>.05)#for#clinical#and#radiographic#outcomes#
Agamy&et&al.&2004344&#
Ib# 12# Percent#
acceptable#
outcome#
Clinical#=#90#
Radiographic#=#90#
FC#=#MTA#(P>.05)#for#clinical#and#radiographic#outcomes#
#
Loh&et&al.&2004193&#
Ia# # # Meta&analysis# FS#=#FC#(P>.10)#for#clinical#and#radiographic#outcomes#
Ibricevic&and&Al9Jame&2003345&#
Ib# 42&48# Percent#
acceptable#
outcome#
Radiographic#=#94# FC#=#FS#(P>.05)#for#clinical#and#radiographic#outcomes#
Dean&et&al.&2002315&&
Ib# 5&12# Percent#
acceptable#
outcome#
Clinical#=#99#
Radiographic#=#87#
FC#=#ES#(P>.05)#for#clinical#and#radiographic#outcomes#
Ibricevic&and&Al9Jame&2000346&
Ib# 20# Percent#
acceptable#
outcome#
Clinical#=#100#
Radiographic#=#97#
FC#=#FS#(P>.05)#for#clinical#and#radiographic#outcomes#
Fuks&et&al.&1997131&#
IIb# 6#to#34#
(mean=2
0)#
Percent#
acceptable#
outcome#
Radiographic#=#84#
#
FC#=#FS#(P>.05)#for#clinical#and#radiographic#outcomes#
*#Shekelle#PG,#Woolf#SH,#Eccles#M,#Grinshaw#J.#Clinical#guidelines:#Developing#guidelines.#BMJ#1999;318:593&596.#
(
!!
! 120!
!Appendix(1B.(Summary(of(published(ferric(sulphate(pulptomy(clinical(controlled(trials,(meta9analysis(and(systematic(reviews.((Formocresol,(FC;(mineral(trioxide(aggregate,(MTA;(calcium(hydroxide,(Ca(OH)2;(ferric(sulphate,(FS;(root(canal(therapy,(RCT;(sodium(hypochlorite,(NaOCl.(
Investigators& *Level&of&Evidence&
Follow9up&&(months)&
FS&Acceptable&Outcomes&(%)&
Outcomes&
Lin&et&al.&2014144& Ia# 18&24# Meta&analysis#and#
systematic#review#
FS#>#Ca(OH)2#(P<.05)#for#clinical#outcome##
FS#>#Ca(OH)2#(P<.05)#for#radiographic#outcome##
FS#>#laser#(P<.05)#for#clinical#outcome##
FS#>#laser#(P<.05)#for#radiographic#outcome#
FS#<#MTA#(P<.05)#for#radiographic#outcome#
Huth&et&al.&2012137& Ib# 36# Total#(clinical#and#
radiographic)#=#76#
FS#=#Er:YAG#=#Ca(OH)2#=#FC##(P>.05)#for#total#(clinical#and#radiographic)#outcome#
Fernandez&et&al.&2012195&
Ib# 24# Radiographic#=#100# FS#=#FC#=#MTA#=#NaOCl#(P>.05)#for#clinical#and#radiographic#outcomes#
Erdem&et&al.&2011182& Ib# 24# Total#(clinical#and#
radiographic)#=#88#
FS#=#MTA#=#FC#(P>.05)#for#clinical#and#radiographic#outcomes#
Doyle&et&al.83& Ib# 6&38#
months#
Radiographic#=#74# MTA#>#FS#(P<.05)#for#radiographic#outcomes#
MTA#&#MTA/FS#>#eugenol&free#FS##(P<.05)#for#radiographic#outcomes#
FS#=#MTA/FS#&#eugenol&free#FS##(P>.05)#for#radiographic#outcomes#
MTA#=#MTA/FS#=#FS#(P>.05)#for#survival#MTA#>#eugenol&free#FS#(P<.05)#for#survival#
Sonmez&et&al.&2008196&
Ib# 24# Radiographic#=#73# FS#=#FC#=#Ca(OH)2#=#MTA#(P>.05)#for#clinical#and#radiographic#outcomes#
Peng&et&al.&200784& IIa# >#6# Meta&analysis## FS#=#FC#(P>.05)#for#clinical#and#radiographic#outcomes#
Huth&et&al.&2005138&#
Ib# 24# Total#(clinical#and#
radiographic)#=#85#
FS#=#Er:YAG#=#FC#(P>.05)#for#total#(clinical#and#radiographic)#outcome#
Casas&et&al.&2004191&&
Ib# 36#months# Radiographic#=#67# RCT#>#FS#(P=.05)#for#radiographic#outcomes#
RCT#>#FS#(P<.05)#for#survival##Casas&et&al.&2004192& Ib# 24#months# Clinical#=#78#
Radiographic#=#59##
FS#=#RCT#(P>.05)#for#radiographic#outcomes#
RCT#>#FS#(P<.05)#for#survival#Casas&et&al.&200382& Ib# 24#months# Radiographic#=#61# FS#=#RCT#(P>.05)#for#radiographic#outcomes#
FS#=#RCT#(P>.05)#for#survival#Loh&et&al.&2004193&#
Ia# # Meta&analysis# FS#=#FC#(P>.10)#for#clinical#and#radiographic#outcomes#
Ibricevic&and&Al9Jame&2003345&
Ib# 42&48# Radiographic#=#92# FS#=#FC#(P>.05)#for#clinical#and#radiographic#outcomes#
Ibricevic&and&Al9Jame&2000346&
Ib# 20# Clinical#=#100#
Radiographic#=#97#
FS#=#FC#(P>.05)#for#clinical#and#radiographic#outcomes#
Fuks&et&al.&1997131&#
IIb# 6#to#34#
(mean=20)#
Radiographic#=#93#
#
FS#=#FC#(P>.05)#for#clinical#and#radiographic#outcomes#
*#Shekelle#PG,#Woolf#SH,#Eccles#M,#Grinshaw#J.#Clinical#guidelines:#Developing#guidelines.#BMJ#1999;318:593&596.#
(
(
(
(
!!!(
! 121!
Appendix(1C.(Summary(of(published(vital(root(canal(therapy(clinical(controlled(trials(and(retrospective(studies.((Formocresol,(FC;(mineral(trioxide(aggregate,(MTA;(calcium(hydroxide,(Ca(OH)2;(ferric(sulphate,(FS;(root(canal(therapy,(RCT;(sodium(hypochlorite,((NaOCl).(
Investigators& *Level&of&Evidence&
Follow9up&&(months)&
RCT&Acceptable&Outcomes&(%)&
Outcomes&
Howley&et&al.&2012219&
Ib# 15&23# Clinical#=#100#
Radiographic#=#73#
RCT#=#FC#(P>.05)#for#clinical#and#radiographic#outcomes#
Aminabadi&et&al.&2008324&
Ib# 24# Clinical#=#96#
Radiographic#=#91#
RCT#>#FC#(P<.05)#for#radiographic#outcomes#
Casas&et&al.&2004191&&
Ib# 36#months# Radiographic#=#86# RCT#>#FS#(P=.05)#for#radiographic#outcomes#
RCT#>#FS#(P<.05)#for#survival##Casas&et&al.&2004192& Ib# 24#months# Clinical#=#100#
Radiographic#=#81#
RCT#=#FS#(P>.05)#for#radiographic#outcomes#
RCT#>#FS#(P<.05)#for#survival#Casas&et&al.&200382& Ib# 24#months# Radiographic#=#91# RCT#=#FS#(P>.05)#for#radiographic#outcomes#
RCT#=#FS#(P>.05)#for#survival#Payne&et&al.&317&&
IIb# 24#months## Total#(clinical#and#
radiographic)#=#83#
#
Yacobi&et&al.&221&&
IIb# 12#to#24#
months#
Radiographic#=#76#at#12#
months#
Radiographic#=#59#at#24#
months#
#
*#Shekelle#PG,#Woolf#SH,#Eccles#M,#Grinshaw#J.#Clinical#guidelines:#Developing#guidelines.#BMJ#1999;318:593&596.#
! 122!
Appendix(1D.(Summary(of(published(mineral(trioxide(aggregate(clinical(controlled(trials(and(retrospective(studies.(Formocresol,(FC;(mineral(trioxide(aggregate,(MTA;(calcium(hydroxide,(Ca(OH)2;(ferric(sulphate,(FS;(root(canal(therapy,(RCT;(sodium(hypochlorite,((NaOCl);(Portland(cement,((PC).(
Investigators& *Level&of&Evidence&
Follow9up&&(months)&
MTA&Acceptable&Outcomes&(%)&
Outcomes&
Lin&et&al.&2014144& Ia# 18&24# Meta&analysis#and#
systematic#review#
FC#1.52#x#more#likely#to#fail#than#MTA#for#
radiographic#outcome#(P<.05)#
Ca(OH)2#2.13#x#more#likely#to#fail#than#FC#for#
clinical#outcome#(P<.05)#
Ca(OH)2#4.55#x#more#likely#to#fail#than#FC#for#
radiographic#outcome#(P<.05)#
Laser#3.76#x#more#likely#to#fail#than#FC#for#clinical#
outcome#(P<.05)#
Laser#3.88#x#more#likely#to#fail#than#FC#for#
radiographic#outcome#(P<.05)#
Shirvani&et&al.&2014145&
Ia# 6&24# Meta&analysis# MTA#relative#risk#of#failure#0.26#compared#to#FC#at#
6#months#
MTA#relative#risk#of#failure#0.37#compared#to#FC#at#
12#months#
MTA#relative#risk#of#failure#0.41#compared#to#FC#at#
24#months#
Mettlach&et&al.&2013143&
Ib# 6&42# Clinical#=#99##
Radiographic#=#95#
Survival#clinical#=#.98#
Survival#radiographic#=#.90#
MTA#>#FC#(P&<.001)#for#radiographic#outcome##
MTA#>#FC#(P<.001)#for#radiographic#survival#FC#5.1#x#more#likely#to#fail#than#MTA#(P<.05)#
Anthonappa&et&al.307&
Ia# 6#to#74#
months#
#
Systematic#review# MTA#=#FC#for#clinical#and#radiographic#outcomes#
Sushynski&et&al.&2012139&&
Ib# 24# Clinical#=#100#
Radiographic#=#97#
MTA#>#FC#(P<.05)#for#radiographic#outcome#
Fernandez&et&al.&2012195&
Ib# 24# Radiographic#=#93# MTA#=#FC#=#FS#=#NaOCl#(P>.05)#for#clinical#and#radiographic#outcomes#
Godhi&et&al.&2011335# IIb# 12# Radiographic#=#96# MTA#=#FC#(P>.05)#for#clinical#and#radiographic#
outcomes#
Erdem&et&al.&2011182& Ib# 24# Total#(clinical#and#
radiographic)#=#88#
MTA#=#FC#=#FS#(P>.05)#for#clinical#and#radiographic#outcomes#
Ansari&and&Ranjpour&2010336&"
Ib# 24# Radiographic#=#95# MTA#=#FC#(P>.05)#for#clinical#and#radiographic#outcomes#
Doyle&et&al.83& Ib# 6&38#
months#
Radiographic#=#96#for#MTA#
and#87#for#MTA/FS##
MTA#>#FS#(P<.05)#for#radiographic#outcomes#
MTA#&#MTA/FS#>#eugenol&free#FS##(P<.05)#for#radiographic#outcomes#
MTA/FS#=#FS#(P>.05)#for#radiographic#outcomes#
MTA#=#MTA/FS#=#FS#(P>.05)#for#survival#MTA#>#eugenol&free#FS#(P<.05)#for#survival#
Simancas9Pallares&et&al.2010337&
Ia# 6#to#<#74# Systematic#review# MTA#>#FC#for#clinical#and#radiographic#outcomes#
Zealand&et&al.&2010140&#
Ib# 6# Clinical#=#100#
Radiographic#=#95#
MTA#>#FC#(P<.05)#for#radiographic#outcome#
Subramanian&et&al.2009338&
Ib# 24# Clinical#=#100##
Radiographic#=#95#
FC#=#MTA#(P<.05)#for#clinical#and#radiographic#outcomes#
Ng&and&Messer&2008340&
Ia# 4&91# Meta&analysis#
#
MTA#>#FC#(P<.05)#for#clinical#and#radiographic#outcomes#
Noorollahian&2008341&
Ib# 24# Clinical#=#100#
Radiographic#=#94#
MTA#=#FC#(P>0.05)#for#clinical#and#radiographic#outcomes#
Sonmez&et&al.&2008196&
Ib# 24# Radiographic#=#67# FC#=#FS#=#Ca(OH)2#=#MTA#(P>.05)#for#clinical#and#radiographic#outcomes#
Aeinehchi&et&al.2007141&
Ib# 6# Clinical#=#100#
Radiographic#=#100#
#
MTA#>#FC#(P<.05)#for#radiographic#outcomes#
Peng&et&al.&2006342& IIa# 1&74# Meta&analysis# MTA#>#FC#(P<.05)#for#radiographic#outcomes#
Holan&et&al.&2005198&#
Ib# 4#to#74#
(mean=38)#
Radiographic#=#97# FC#=#MTA#(P>.05)#for#radiographic#outcomes#
! 123!
Agamy&et&al.&2004344&#
Ib# 12# Clinical#=#100#for#gray#MTA#
and#80#for#white#MTA#
Radiographic#=#100#for#
gray#MTA#and#80#for#white#
MTA#
Gray#MTA#=#white#MTA#=#FC#(P>.05)#for#clinical#and#radiographic#outcomes#
#
*#Shekelle#PG,#Woolf#SH,#Eccles#M,#Grinshaw#J.#Clinical#guidelines:#Developing#guidelines.#BMJ#1999;318:593&596.#
! 124!
Appendix(1E.(Summary(of(published(pulp(therapy(of(primary(incisor(investigations.(Formocresol,(FC;(mineral(trioxide(aggregate,(MTA;(calcium(hydroxide,(Ca(OH)2;(ferric(sulphate,(FS;(root(canal(therapy,(RCT;(NaOCL,(sodium(hypochlorite;(ZOE,(zinc(oxide(eugenol.(
!Investigators& *Level&of&
Evidence&Follow9up&&(months)&
Acceptable&Outcomes&(%)& Outcomes&
Howley&et&al.&2012219&
Ib# 15&23# Clinical#
FC#pulpotomy#=#100#
RCT#=#100#
#
Radiographic#
FC#pulpotomy#=#89#
RCT#=#73#
RCT#=#FC#pulpotomy#(P>.05)#for#clinical#and#radiographic#outcomes#
Aminabadi&et&al.&2008324&
Ib# 24# Clinical##
FC#pulpotomy#=#87#
RCT#=#96#
#
Radiographic##
FC#pulpotomy#=#76#
RCT#=#91#
RCT#>#FC#pulpotomy#(P<.05)#for#radiographic#outcomes#
Primosch&et&al.&222&Retrospective#study&
III# 16&53#
(mean=34)#
Radiographic##
RCT#=#81#
#
Casas&et&al.&2004191&&
Ib# 36# Clinical#
FS#pulpotomy#=#78#
RCT#=#100#
#
Radiographic#
FS#pulpotomy#=#59#
RCT#=#81#
RCT#>#FS#pulpotomy#(P=.05)#for#radiographic#outcomes#
RCT#>#FS#pulpotomy#(P<.05)#for#survival##
Payne&et&al.&317&&
IIb# 24## Total#(clinical#and#
radiographic)#
RCT#=#83#
#
Yacobi&et&al.&221&&
IIb# 12#to#24# Radiographic##
RCT#=#76#at#12#months#
RCT#=#59#at#24#months#
#
Flaitz&et&al.&319&Retrospective#study&
III# 12&65#
(mean=37)#
Radiographic##
FC#pulpotomy#=#72#
RCT#=#86##
#
Coll&et&al.&207&Retrospective#study&
III# Mean#
Pulpotomy#
=#44##
IPT#=#42#
RCT#=#46##
Total#(clinical#and#
radiographic)##
FC#pulpotomy#=#86#
IPT#=#92#
RCT#=#78#
#
#
*#Shekelle#PG,#Woolf#SH,#Eccles#M,#Grinshaw#J.#Clinical#guidelines:#Developing#guidelines.#BMJ#1999;318:593&596.#
! 125!
! 126!
Chapter 2. Manuscript
Mineral Trioxide Aggregate/Ferric Sulfate Pulpotomy for Vital Primary Incisors:
A Randomized Controlled Trial
2.1. Abstract
Purpose: To compare clinical and radiographic outcomes and survival of mineral
trioxide aggregate/ferric sulfate (MTA/FS) pulpotomy and root canal therapy (RCT) in
carious vital primary maxillary incisors.
Methods: Asymptomatic carious vital primary incisors with pulp exposure in healthy
children aged 18 to 46 months were allocated randomly to receive MTA/FS pulpotomy or
RCT. FS was used to induce hemostasis after coronal pulp amputation prior to the
placement of MTA in MTA/FS pulpotomy treated incisors. Clinical and radiographic
post-treatment assessments occurred at 6-month intervals for up to 40 months. Two
disinterested raters classified each incisor into one of the following radiographic
outcomes: N=incisor without pathologic change; Po=pathologic change present, follow-
up recommended; Px=pathologic change present, extract.
Results: Eighteen-month outcomes demonstrated no statistical difference in clinical
outcomes for MTA/FS pulpotomy and RCT incisors (P=.52). No statistical difference in
radiographic outcomes for MTA/FS pulpotomy and RCT for Px outcomes was
demonstrated (P=.63). Survival analysis demonstrated no statistically significant
difference in survival for MTA/FS pulpotomy and RCT incisors (P=.22) over a 6 to 40
month follow-up interval.
Conclusions: MTA/FS pulpotomy is an effective treatment for carious vital primary
incisors.
! 127!
2.2. Objectives
1. To compare clinical and radiographic outcomes of MTA/FS pulpotomy and RCT
in carious vital primary maxillary incisors.
2. To compare the survival of vital primary incisors treated with MTA/FS
pulpotomy and RCT.
3. To investigate the association between radiographic findings and MTA/FS
pulpotomy and RCT outcomes.
! 128!
2.3. Introduction
Dental caries is the most common chronic disease in children.1 Primary maxillary
incisors are teeth commonly affected by caries in young children. Caries often extends to
the pulps of primary maxillary incisors necessitating either pulp therapy with restoration
or extraction. The premature loss of primary maxillary incisors can adversely affect a
child’s dental occlusion, ability to properly size food boluses for swallowing, speech
articulation, facial esthetics and psychosocial development.2-10 Pulp treatment of
cariously exposed vital primary incisors may prevent premature tooth loss as well as
eliminate pain. Currently, there is a paucity of outcome investigations with regards to
pulp therapy in primary incisors.
Pulpotomy is the amputation of inflamed coronal pulp tissue often followed by the
placement of a medicament on the remaining vital radicular pulp tissue. The pulpotomy
is the vital primary molar pulp technique used by most pediatric dentists, the most
common vital primary molar pulp technique taught in pediatric dentistry specialty
programs and the accepted standard of care for carious exposures of vital primary molars
in North America.11-12 There is currently no consensus with regard to standard of care for
treatment of vital primary incisors. Thirty-eight percent of a randomly selected sample of
American Academy of Pediatric Dentistry (AAPD) members preferred pulpotomy for the
treatment of vital primary incisors, 33 percent preferred root canal therapy (RCT) and 23
percent preferred indirect pulp therapy.13 Of the 33 percent of survey respondents that
reported they preferred RCT, 56 percent reported that they preferred RCT as it was the
preferred technique taught in their specialty program and 33 percent reported their belief
! 129!
that incisor pulpotomy had poor outcomes. Little evidence exists to substantiate the
perception that vital primary incisor pulpotomy has poor outcomes.
A variety of techniques have been investigated for the treatment of primary vital molars.
Recently, superior outcomes for mineral trioxide aggregate (MTA) primary molar
pulpotomy have been reported when compared to other common pulpotomy medicaments
including formocresol (FC) and ferric sulfate (FS).14-19
No outcome investigation assessing MTA pulpotomy in primary incisors has been
published. MTA pulpotomy could offer a clinically efficient or cost effective therapy for
vital primary incisor pulps compared to commonly used alternative therapies such as the
5-minute FC pulpotomy or RCT technique. Using FS to induce hemostasis after coronal
pulp amputation prior to placement of MTA could further improve the clinical efficiency
of the pulpotomy procedure.19
2.4. Methods
Approval to perform the investigation was obtained from the Research Ethics Board of
The Hospital for Sick Children, Toronto, Canada (No. 1000019443). The investigation
was registered with ClinicalTrials.gov Protocol and Registration System (ID
NCT02019563). The procedures, possible risks, discomforts and possible benefits were
explained to the parents of the patients involved at least 24 hours prior to being offered
participation into the study. Informed consent was obtained by the pediatric dentist
providing oral rehabilitation.
! 130!
Healthy children, 18 to 42 months of age, with one or more carious asymptomatic
primary maxillary incisors where removal of dental caries was likely to produce vital
pulp exposure were invited to participate in the investigation. Eligible incisors had no
signs or symptoms of inflammation extending beyond the coronal pulp and were
restorable. Exclusion criteria included history of spontaneous pain or lingering provoked
pain, swelling, fistula or sinus tract, tenderness to percussion and pathological mobility.
Incisors with preoperative radiographic evidence of periapical or periradicular
radiolucency, a widened periodontal ligament (PDL) space, physiological resorption,
incomplete root formation, internal or external root resorption, pulp canal obliteration
(PCO) or pulp calcifications were also excluded.
Sample size was determined using a sample size calculation program (PS Power and
Sample Size Calculation Program, Version 3.0.43). Sample size was calculated using
outcomes from Casas et al. comparing FS and vital primary RCT outcomes.20 Sample
size calculation produced a required sample size of 61 incisors per group to detect a
significant difference (80% power, two-sided 5% significance level).
Five pediatric dentists (PLJ, MJC, EJB, RDF, IYS) completed all pulp therapy. Each
subject was randomly allocated to one of two treatment groups using a computer
generated simple random numbers sequence. Each subject received the same pulp
therapy on all eligible incisors. The pediatric dentist, nurse or assistant would assign
subjects to the appropriate treatment group at the time of dental surgery. The
randomization sequence was concealed until treatment was initiated. One investigator
! 131!
(TDN) generated the randomization sequence and performed random quality assurance
checks to ensure compliance with the randomization protocol. All other contributors to
the study were blinded to generation and implementation of the treatment assignment.
All treatment was provided under general anesthesia with rubber dam isolation.
Following caries removal and pulp exposure, the pulp chamber was accessed using a
sterile no. 56 bur in a water-cooled high-speed handpiece. The access was refined using
a sterile no. 4 or 6 round bur in a slow-speed handpiece. The remaining pulp was treated
using either one of the two of the following pulp therapy techniques:
MTA/FS pulpotomy. The coronal pulp was amputated to a depth of approximately 2
millimeters below the free gingival margin with a no. 56 high-speed bur or slow speed
no. 4 or 6 round bur. Ferric sulfate 15.5 percent solution (Astringedent®, Ultradent
Products Inc, Salt Lake City, UT, USA) was applied using a syringe (Dento-Infusor®,
Ultradent Products Inc, Salt Lake City, UT, USA) to the radicular pulp surface for 10 to
15 seconds. The pulp chamber was then flushed with sterile water from an air-water
syringe. If hemostasis was not achieved the incisor was eliminated from the study. If
hemostasis was achieved, MTA (Tooth-colored ProRoot®, Dentsply, Tulsa Dental, Tulsa,
OK, USA) was applied to the amputated pulp surface to a thickness of not less than 1 mm
using an amalgam carrier. MTA was prepared according to the manufacturer’s
instructions. Excess MTA was removed and the pulp chamber was sealed with a layer of
light cured glass ionomer (VitrebondTM Plus, 3M Dental Products, St. Paul, MN, USA).
A retentive undercut was prepared within the canal using a no. 4 slow speed round bur.
! 132!
This allowed for a more retentive resin core when the incisors were restored with an acid
etch resin (Spectrum® TPH®, Dentsply/Caulk, Milford, DE, USA).
RCT. Pulp tissue was removed en bloc using 2 or more endodontic files (Hedstrom®,
Dentsply, Tulsa Dental, Tulsa, OK, USA). If the pulp was not fully removed in its
entirety in the initial attempt, this step was repeated until all pulp tissue was extirpated.
The canal was then irrigated with sterile water, lightly air dried using an air-water syringe
and obturated with non-reinforced ZOE (Zinc Oxide Powder and Eugenol USP, Keystone
Industries, Myerstown, PA, USA) using a spiral paste filler (Lentulo® Spiral Filler,
Dentsply, Tulsa Dental, Tulsa, OK, USA). Excess ZOE was removed and a retentive
undercut was prepared within the canal using a no. 4 slow speed round bur. The pulp
chamber was sealed with a thin layer of light cured glass ionomer (VitrebondTM Plus, 3M
Dental Products, St. Paul, MN, USA) and restored with acid etch resin (Spectrum®
TPH®, Dentsply/Caulk, Milford, DE, USA).
Incisors were assessed clinically and radiographically at 6-month intervals up to 40
months post-treatment. All follow-up data was recorded on preprinted data collection
sheets, entered into a computer database (FileMaker Pro 11, FileMaker Inc, Santa Clara,
MN, USA) and exported into a spreadsheet (Microsoft ExcelTM 2011, Microsoft Canada
Inc, Missisauga, ON, Canada). A single investigator (TDN), who did not complete any
pulp therapy or participate in radiographic evaluation, performed all the clinical
assessments. At each follow-up assessment, subjects and their parents/guardians were
asked to report any history of pain and/or swelling related to the pulp treated incisors.
! 133!
Clinical findings assessed included presence or absence of the treated incisor, presence of
restoration and if present whether the restoration was intact or not, localized gingival
erythema, swelling, fistula/sinus tract, pathological tooth mobility, tenderness to
percussion and tenderness to palpation. Clinical findings considered unacceptable
outcomes included spontaneous pain, tenderness to percussion, fistula/sinus tract, soft
tissue swelling and/or pathological tooth mobility associated with the pulp treated incisor.
Radiographic outcomes were categorized using the rating scale published in Doyle et al.20
Two disinterested experienced pediatric dentists (DRF, SSC) classified each treated
incisor into one of three outcomes based on radiographic evaluation: N=incisor without
pathologic change; Po=pathologic change present, follow-up recommended; and
Px=pathologic change present, extract. Incisors rated N or Po were considered an
acceptable radiographic outcome while incisors rated as Px were considered
unacceptable. Raters were not given specific radiographic criteria for each outcome
classification but were asked to use their clinical judgment. Raters were blinded to any
patient identifying information, date of the recall and date of treatment. Evaluators
assessed radiographs that were randomized by patient and date of recall.
Radiographs were taken of all treated incisors with a maxillary no. 2 occlusal phosphor
storage plate (ScanXTM, Air Techniques Inc, Melville, NY, USA) at each assessment. All
radiographs were available in digital format and were projected onto a 21.5 inch
widescreen LCD Picture Archiving and Communication System (PACS) diagnostic
monitor (ZR22w Monitor, HP, Palo Alto, CA, USA) at a resolution of 1920 x 1080 @ 60
! 134!
Hz. Radiographic findings assessed included presence or absence of periapical
radiolucency, pathological external root resorption, widened PDL space, physiological
root resorption, internal root resorption, PCO, dentin bridge and whether the restoration
was intact or not.
Univariate logistic regression was used to compare outcomes of incisors treated by
MTA/FS pulpotomy and RCT. Clinical and radiographic outcomes of each intervention
were calculated considering previous and unacceptable outcomes at the time of recall. A
binary logistic generalized estimating equation model was used to analyze predictor
variables such as age, gender, tooth and treatment provider between the two treatment
groups (α-level=0.05) given as an odds ratio with 95% confidence interval (OR±95% CI).
Univariate logistic regression was used to assess the association between pathological
radiographic findings and radiographic outcomes. Chi-square tests were applied to assess
the effect of radiographic findings on radiographic outcomes. Chi-square tests and t-tests
were used to compare differences in demographics. All tests were interpreted at a 0.05
level of significance. The inter-rater and intra-rater reliability were calculated and
interpreted using Cohen's unweighted kappa statistic. Subjects and incisors were
followed up at 6-month intervals up to 40 months.
Kaplan-Meier survival curves were generated for the MTA/FS pulpotomy and RCT
treatment groups. The log-rank test was used to statistically compare survival of incisors.
One treated incisor was randomly selected from each subject for survival analysis to
preserve independence of observations. Incisors from all recalled subjects, regardless of
! 135!
follow-up time, were included in the survival analysis. All data was entered into a
Microsoft ExcelTM spreadsheet and analyzed using SAS® (SAS®, SAS Institute Inc.,
Cary, NC, USA).
2.5. Results
Subjects were recruited at The Hospital for Sick Children between September 2010 and
September 2012. Inclusion into the study was offered to 115 eligible subjects (54 males;
61 females). Twenty subjects (10 males; 10 females) declined participation and 25
subjects (11 males; 14 females) were declined participation into the study by the surgeon.
Reasons subjects were declined participation by the surgeon included no pulp exposure
upon caries removal or the pulp was necrotic. A single incisor was declined participation
because hemostasis was not achieved after 10 to 15 second application of FS. A total of
171 maxillary primary incisors in 70 subjects were enrolled in the study (Figure 1). The
average age of subjects at the time of treatment was 31 months with a standard deviation
of 6 months and subjects ages ranged between 18 and 46 months. The MTA/FS group
consisted of 100 incisors in 41 subjects (19 males; 22 females) and the RCT group
consisted of 71 primary incisors in 29 subjects (14 males; 15 females). No difference in
gender distribution (P=.90, chi-square test) or age at the time of treatment (P=.27, sample
t-test) was shown between the MTA/FS pulpotomy and RCT groups. When the logistic
regression analyses were corrected for age, gender, tooth and treatment provider, the
effect of age, gender, tooth and treatment provider were not significant (P>.05, chi-square
test).
! 136!
At 12-month follow-up, 65 of 70 (93 percent) of subjects and 157 of 171 (92 percent) of
incisors returned for follow-up. Subjects lost included 3 subjects that could not be
contacted and 2 subjects that declined an offer for a recall appointment. Incisors lost
included 12 to follow-up or drop out and 2 to trauma. At 18-month follow-up, 57 of 70
(81 percent) of subjects and 132 of 171 (77 percent) of incisors returned for follow-up.
Subjects lost included 7 subjects that could not be contacted and 6 subjects that declined
an offer for a recall appointment. Incisors lost included 30 to follow-up or drop-out, 7 to
trauma and 2 to exfoliation (Figure 1).
No difference between MTA/FS pulpotomy and RCT clinical outcomes were
demonstrated at 12-month (P=.51, chi-square test) and 18-month (P=.52, chi-square test)
follow-up. Acceptable clinical outcomes were demonstrated in 98 percent (88 of 90) of
MTA/FS pulpotomy and 100 percent (67 of 67) of RCT incisors at 12-month and 96
percent (68 of 71) of MTA/FS pulpotomy and 99 percent (60 of 61) of RCT incisors at
18-month follow-up. Of the 4 incisors considered to have an unacceptable clinical
outcome, 2 incisors were associated with a fistula/sinus tract, 1 incisor was associated
with a history of spontaneous pain and tenderness to percussion and 1 incisor was
associated with soft tissue swelling, pathological tooth mobility and tenderness to
percussion.
Radiographic outcomes were not statistically different between MTA/FS pulpotomy and
RCT incisors for Px outcomes at 12-month (P=.21, chi-square test) and 18-month (P=.63,
chi-square test) follow-up (Table 1 and 2). Acceptable radiographic outcomes of incisors
! 137!
rated N or Po comprised 97 percent (87 of 90) of MTA/FS pulpotomy and 91 percent (61
of 67) of RCT incisors at 12-month follow-up and 92 percent (65 of 71) of MTA/FS
pulpotomy and 89 percent (54 of 61) of RCT incisors at 18-month follow-up.
Incisors demonstrating any pathological change or rated Po or Px comprised 8 percent (7
of 90) of MTA/FS pulpotomy and 22 percent (15 of 67) of RCT incisors at 12-month
follow-up and 10 percent (7 of 71) of MTA/FS pulpotomy and 21 percent (13 of 61) of
RCT incisors at 18-month follow-up. RCT incisors were statistically significantly more
likely to demonstrate any pathologic radiographic change (Po or Px) than MTA/FS
pulpotomy incisors at 12 months post-treatment (P=.04, chi-square test) . A similar
tendency was not demonstrated at 18-months post-treatment (P=0.1, chi-square test).
Incisors exhibiting a periapical radiolucency (P<.0001; chi-square test), external root
resorption (P<.0001; chi-square test), widened PDL space (P<.0001; chi-square test) or
internal root resorption (P=.009; chi-square test) on post-treatment radiographic
examination were significantly more likely to have a Px outcome.
Intra-rater agreement was perfect for incisors with outcome Px (K=1.0, Cohen’s kappa).
Inter-rater agreement was almost perfect for incisors with outcome Px (K=0.84; Cohen’s
kappa).
Outcome data from treated incisors of 66 of 70 (94 percent) of subjects who returned for
recall during the 6 to 40 month follow-up period contributed to the survival analysis. To
! 138!
ensure statistical independence of the observations, each subject contributed only one
incisor to the survival analysis by random draw. Thirty-eight observations for MTA/FS
pulpotomy and 28 observations for RCT incisors were available for survival analysis.
Incisors extracted due to unacceptable clinical outcomes or rated as Px were considered to
not meet the criteria for survival. Incisors were censored if lost to follow-up, exfoliated,
lost to trauma or had a non-occurrence of a failure before the trial end. Kaplan-Meier
survival curves for treated molars in each group are shown in Figure 3. The survival rate
was 0.94 for MTA/FS pulpotomy and 0.92 for RCT at 12-month follow-up and 0.87 for
MTA/FS pulpotomy and 0.88 for RCT at 18-month follow-up. Survival analysis
demonstrated no significant difference in survival for MTA/FS pulpotomy and RCT
incisors (P=.27, log-rank test) over a 6 to 40 month follow-up interval.
2.6. Discussion
Twelve- and 18-month clinical and radiographic outcomes and survival analysis
demonstrated no statistically significant difference between MTA/FS pulpotomy and
RCT treated asymptomatic vital primary incisors with carious pulp exposure. However,
RCT treated incisors demonstrated on radiographic examination, significantly more
pathological changes (Po or Px) than MTA/FS pulpotomy treated incisors at 12 months
post-treatment. This difference was not demonstrated at 18-months post-treatment.
Only 3 other randomized controlled trials have compared pulpotomy and RCT outcomes
in vital primary incisors. Howley et al. compared the clinical and radiographic outcomes
of FC pulpotomy and RCT up to 23 months post-treatment.13 Clinical and radiographic
! 139!
outcomes of FC pulpotomy and RCT were not statistically different (P>0.05).
Aminabadi et al. also compared the clinical and radiographic outcomes of FC pulpotomy
and RCT.21 Radiographic outcomes were significantly more favorable for RCT than FC
pulpotomy 2-years post-treatment (P<.05). Casas et al. compared FS pulpotomy and
RCT outcomes in asymptomatic vital primary incisors.20 The study found no significant
difference in clinical or radiographic outcomes of FS pulptomy and RCT. However,
RCT incisors demonstrated a significantly higher survival rate than FS pulpotomy
incisors 2-years post-treatment (P=.04). Methodology and small sample size issues limit
the interpretatively of the outcomes from Aminabadi et al. and Casas et al.
Esthetics is a reported concern of clinicians and parents in pulp treated primary incisors.22
MTA, ZOE, Endoflas and iodoform are obturation materials reported to have the
potential to discolor coronal tooth structure in primary teeth. Tooth-colored ProRoot
MTA has demonstrated gray discoloration in both in vivo and in vitro studies.23-25 The
mechanism of MTA discoloration is still not fully understood, but recent evidence
suggests tooth discoloration is associated with metallic black bismuth oxide formed from
the reaction of bismuth oxide with light in a non-oxygenated environment.26-28
Prominent gray discoloration of MTA can cause teeth to change in color or show through
restorations and effect esthetics. Discoloration of MTA may not be a concern in the
future as manufactures are distributing MTA where zirconium oxide has replaced
bismuth oxide as the radiopacifier. Also, alternative materials are being manufactured
and distributed (e.g. BioDentine and Portland cement) that are purported to have similar
properties to MTA and are color-stable.27
! 140!
There is a perception among some pediatric dentists “that pulpotomies do not work in
primary incisors.”13 The AAPD guideline on pulp therapy states a pulpotomy is indicated
when caries removal results in vital pulp exposure in primary teeth.29 MTA/FS
pulpotomy is an acceptable pulp therapy technique for asymptomatic vital primary
incisors with carious pulp exposure. The advantage of MTA/FS pulpotomy when
compared to RCT technique in primary incisors is clinical efficiency.
2.7. Conclusion
MTA/FS pulpotomy is an effective treatment for carious vital primary incisors with pulp
exposure.
2.8. Acknowledgements
The investigators would like to thank Drs. Sonia Chung and David Farkouh for rating
radiographs and Drs. Randi Fratkin and Ihab Suwwan for providing clinical care to a
portion of the study subjects. We would also like to thank Derek Stephens for statistical
support throughout the investigation.
! 141!
2.9. References
1. US Department of Health and Human Services. Oral Health in America: A Report of the Surgeon General-Executive Summary. Rockville, MD: US Department of Health and Human Services, National Institute of Dental and Craniofacial Research, National Institutes of Health; 2000.
2. Acs G, Shulman R, Ng MW, Chussid S. The effect of dental rehabilitation on the body weight of children with early childhood caries. Pediatr Dent 1999;21(2):109-113.
3. Mouradian WE, Wehr E, Crall JJ. Disparities in children's oral health and access to dental care. JAMA 2000;284(20):2625-2631.
4. Shaw WC, Meek SC, Jones DS. Nicknames, teasing, harassment and the salience of dental features among school children. Br J Orthod 1980;7(2):75-80.
5. Riekman GA, el Badrawy HE. Effect of premature loss of primary maxillary incisors on speech. Pediatr Dent 1985;7(2):119-122.
6. Filstrup SL, Briskie D, da Fonseca M, Lawrence L, Wandera A, Inglehart MR. Early childhood caries and quality of life: child and parent perspectives. Pediatr Dent 2003;25(5):431-440.
7. Woo D, Sheller B, Williams B, Mancl L, Grembowski D. Dentists' and parents' perceptions of health, esthetics, and treatment of maxillary primary incisors. Pediatr Dent 2005;27(1):19-23.
8. Lamberghini F, Kaste LM, Fadavi S, Koerber A, Punwani IC, Smith EB. An association of premature loss of primary maxillary incisors with speech production of bilingual children. Pediatr Dent 2012;34(4):307-311.
9. Adewumi AO, Horton C, Guelmann M, Dixon-Wood V, McGorray SP. Parental perception vs. professional assessment of speech changes following premature loss of maxillary primary incisors. Pediatr Dent 2012;34(4):295-299.
10. Shaw WC. The influence of children's dentofacial appearance on their social attractiveness as judged by peers and lay adults. Am J Orthod 1981;79(4):399-415.
11. American Academy of Pediatric Dentistry. Guideline on pulp therapy for primary and immature permanent teeth: Reference Manual 2011-12. Pediatr Dent 2011;33:212-219.
12. Walker LA, Sanders BJ, Jones JE, et al. Current trends in pulp therapy: a survey analyzing pulpotomy techniques taught in pediatric dental residency programs. J Clin Pediatr Dent 2013;80(1):31-35.
13. Howley B, Seale NS, McWhorter AG, Kerins C, Boozer KB, Lindsey D. Pulpotomy versus pulpectomy for carious vital primary incisors: randomized controlled trial. Pediatr Dent 2012;34(5):112-119.
14. Lin PY, Chen HS, Wang YH, Tu YK. Primary molar pulpotomy: A systematic review and network meta-analysis. J Dent. Feb 7 2014.
! 142!
15. Shirvani A, Asgary S. Mineral trioxide aggregate versus formocresol pulpotomy: a systematic review and meta-analysis of randomized clinical trials. Clin Oral Invest 2014.
16. Simancas-Pallares MA, Diaz-Caballero AJ, Luna-Ricardo LM. Mineral trioxide aggregate in primary teeth pulpotomy. A systematic literature review. Med Oral Patol Oral Cir Bucal 2010;15(6):e942-946.
17. Mettlach SE, Zealand CM, Botero TM, Boynton JR, Majewski RF, Hu JC. Comparison of Mineral Trioxide Aggregate and Diluted Formocresol in Pulpotomized Human Primary Molars: 42-month Follow-up and Survival Analysis. Pediatr Dent 2013;35(3):87-94.
18. Aeinehchi M, Dadvand S, Fayazi S, Bayat-Movahed S. Randomized controlled trial of mineral trioxide aggregate and formocresol for pulpotomy in primary molar teeth. Int Endod J. Apr 2007;40(4):261-267.
19. Doyle TL, Casas MJ, Kenny DJ, Judd P. Mineral trioxide aggregate produces superior outcomes in vital primary molar pulpotomy. Pediatr Dent 2010;32(1):41-47.
20. Casas MJ, Kenny DJ, Johnston DH, Judd PL, Layug MA. Outcomes of vital primary incisor ferric sulfate pulpotomy and root canal therapy. J Can Dent Assoc 2004;70(1):34-38.
21. Aminabadi NA, Farahani RM, Gajan EB. A clinical study of formocresol pulpotomy versus root canal therapy of vital primary incisors. J Clin Pediatr Dent 2008;32(3):211-214.
22. Kupietzky A, Waggoner WF, Galea J. The clinical and radiographic success of bonded resin composite strip crowns for primary incisors. Pediatr Dent. 2003;25(6):577-581.
23. Boutsioukis C, Noula G, Lambrianidis T. Ex vivo study of the efficiency of two techniques for the removal of mineral trioxide aggregate used as a root canal filling material. J Endod. 2008;34(10):1239-1242.
24. Maroto M, Barberia E, Planells P, Garcia Godoy F. Dentin bridge formation after mineral trioxide aggregate (MTA) pulpotomies in primary teeth. Am J Dent. 2005;18(3):151-154.
25. Watts JD, Holt DM, Beeson TJ, Kirkpatrick TC, Rutledge RE. Effects of pH and mixing agents on the temporal setting of tooth-colored and gray mineral trioxide aggregate. J Endod. 2007;33(8):970-973.
26. Felman D, Parashos P. Coronal tooth discoloration and white mineral trioxide aggregate. J Endod. 2013;39(4):484-487.
27. Valles M, Mercade M, Duran-Sindreu F, Bourdelande JL, Roig M. Influence of light and oxygen on the color stability of five calcium silicate-based materials. J Endod. 2013;39(4):525-528.
! 143!
28. Valles M, Mercade M, Duran-Sindreu F, Bourdelande JL, Roig M. Color stability of white mineral trioxide aggregate. Clin Oral Investig. 2013;17(4):1155-1159.
29. American Academy of Pediatric Dentistry. Guideline on pulp therapy for primary and immature permanent teeth: Reference Manual 2011-12. Pediatr Dent 2011:212-219.
! 144!
2.10. Figures & Tables
Figure 1. Flowchart demonstrating the number of incisors and subjects recruited, treated
and recalled at 12- and 18-month follow-up.((
!
Assessed for eligibility (115 subjects)
Excluded (45 subjects) ♦!!!Not meeting inclusion criteria (25
subjects) ♦!!!Declined to participate (20 subjects)
Analysed (n= 90 incisors)
!
Lost to follow-up or declined participation (n= 9 incisors)
Lost to trauma (n= 1 incisors) Lost to exfoliation (n= 0 incisors)
Allocated to MTA/FS pulpotomy (n= 100 incisors)!
Lost to follow-up or declined participation (n= 3 incisors)
Lost to trauma (n= 1 incisors) Lost to exfoliation (n= 0 incisors)
Allocated to RCT (n= 71 incisors)
!
Analysed (n= 67 incisors)!
Allocation)
12,Month)Analysis)
Follow,Up)
Randomized by subject
Enrollment)
Analysed (n= 71 incisors)
!
Lost to follow-up or declined participation (n= 14 incisors)
Lost to trauma (n= 3 incisors) Lost to exfoliation (n= 2 incisors)
Lost to follow-up or declined participation (n= 4 incisors)
Lost to trauma (n= 2 incisors) Lost to exfoliation (n= 0 incisors)
Analysed (n= 61 incisors)!
18,Month)Analysis))
Follow,Up))
! 145!
Table 1 and 2. Radiographic outcomes of MTA pulpotomy and RCT treated incisors at
12- and 18-month follow-up.
!
! 146!
Figure 2a and 2b. Example of incisors treated with MTA/FS pulpotomy (top) and RCT
(bottom).
! 147!
Figure 3. Kaplan-Meier Curves for MTA/FS pulpotomy and RCT treated primary
incisors in subjects returning 6 to 40 months post-treatment. Censored subjects are
indicated with a “+”.
! 148!
2.11. Appendix
2.11.1. Protocol
A prospective outcome investigation of mineral trioxide aggregate pulpotomy in
primary maxillary incisors
Principal investigator: Dr Peter L Judd
Co-investigators: Dr Michael J Casas, Dr. Edward J Barrett
Statement of the problem
The primary maxillary incisors are important in masticatory function, occlusal
development, articulation and self-esteem1. Cariously exposed vital pulps of primary
incisors require pulp treatment to avoid infection, pain and premature tooth loss.
Unfortunately, there is a paucity of investigations of maxillary incisor pulp treatment.
The formocresol pulpotomy is the most popular vital primary molar pulp technique in
North America and the UK.2,3 However, concerns about the safety of the active
component of formocresol, 19% formalin, persist.4 Concerns include immune
sensitization, mutagenicity and carcinogenicity 5,6. Interactions between formaldehyde
and rat DNA have produced experimental tumours. As a consequence, formaldehyde
represents a substantial human carcinogenic risk.7 The International Agency for Research
! 149!
on Cancer (IARC) of the World Health Organization classified formaldehyde as a known
human carcinogen.8
The root canal/zinc oxide and eugenol (RCT/ZOE) technique has been shown to have the
best outcomes and significantly higher survival rates than other vital pulp techniques for
treatment of carious exposed, inflamed pulps of the primary incisors.1,9 Consequently, it
is the clinical standard for vital pulp therapy for primary incisors at The Hospital for Sick
Children. However, RCT/ZOE has not been accepted into the mainstream of the dental
profession because it is a technically demanding procedure, expensive to provide and
requires a longer treatment time than pulpotomy procedures.
Mineral trioxide aggregate (MTA) is dental cement that consists of discrete crystals (87%
calcium, 3% silica, 10% oxygen) and amorphous structure (33% calcium, 49%
phosphate, 2% carbon, 3% chloride, 6% silica). It has a pH of 12.5 and sets to solid
consistency in under three hours with a compressive strength of 40 MPa at 24 hours.10
MTA is biocompatible and is associated with dental hard tissue formation in contact with
the dental pulp.10-12 MTA pulpotomy produced superior clinical and radiographic
outcomes in primary molars.1,12,13, If MTA primary molar pulpotomy outcomes were
replicated in primary incisor pulpotomies, a simpler, less time intensive cost-effective
therapy for vital primary incisor pulps would be available for children with primary
incisor caries. Furthermore, using ferric sulfate (FS) to induce haemostasis after coronal
pulp amputation prior placement of MTA would improve the clinical efficiency of the
! 150!
procedure. FS application prior to MTA placement did not significantly alter outcomes
for MTA primary molar pulpotomies.13
Objective of this investigation
The objective of this investigation is to compare statistically the clinical and radiographic
outcomes of MTA pulpotomies and RCT/ZOE in primary maxillary incisors. This
investigation will compare one and two year outcomes of conventional RCT/ZOE
(control) with the MTA pulpotomy. The experimental group will have MTA applied to
amputated pulp stump after hemostasis is achieved using FS. The control group will have
the pulp tissue removed completely and the empty canal filled with ZOE.
Materials and Methods
Typical children with one or more carious primary maxillary incisors where removal of
dental caries will likely to produce a vital pulp exposure will be eligible for the protocol.
The incisors included in the study will exhibit no radiographic evidence of physiological
or pathological root resorption or periapical radiolucencies. Children with maxillary
incisors that present with an associated swelling will not be included in the study. This
investigation will be submitted to and approved by the Research Ethics Board at The
Hospital for Sick Children prior to commencement. A consent form will be completed
and signed for each subject prior to treatment. Dentists will offer inclusion to eligible
subjects and their parents in person at the time of initial consultation and treatment
planning for oral rehabilitation for early childhood caries. Only dentists will offer
! 151!
inclusion in this trial. Specialist dentists who complete or supervise treatment for eligible
children will acquire consent.
The pulp technique used will be determined by random selection and will be consistent
for each child (each child will receive the same pulp treatment on all eligible incisors).
The inclusion criteria for pulp treatment are the same for all eligible incisors:
asymptomatic exposure of vital pulp by caries, no clinical or radiographic evidence of
pulp degeneration (such as internal/external root resorption and/or periapical bone
destruction or swelling) and possibility of proper restoration of the tooth.
The pulp treatment techniques will be carried out as follows:
1. ZOE/RCT (control)
A. After complete removal of all caries, open pulp chamber
B. Pulp tissue removed in its entirety with two or more Haedstrom
endodontic files
C. Canal irrigated with water followed by light air dry
D. Canal filled with non-reinforced ZOE using spiral paste filler
E. Excess ZOE removed from coronal chamber and retentive core
prepared using #4 slow speed round bur
F. Apply thin layer of light-cured glass ionomer dentin liner
G. Tooth restored with acid etch resin restoration
2. MTA/FS pulpotomy
A. After complete removal of all caries, open pulp chamber
! 152!
B. Remove coronal pulp to a depth of 2mm below free gingival margin with
high speed bur
C. Apply 15.5% solution of FS (Astringedent®) using Dento-Infusor® syringe
to amputated pulp surface for 10-15 seconds
D. Flush Astringedent® from pulp chamber with water.
(i) If bleeding does not stop after a 15 second application of
Astringedent®, then proceed to a primary ZOE/RCT or extraction.
This tooth is no longer eligible for this study.
E. Apply MTA paste to cover over the exposed amputated pulp surface and a
margin of not less that 1mm beyond the pulp dentin interface
F. Apply thin layer of light-cured glass ionomer dentin liner
G. Restore with acid etch resin
One hundred sixty subjects will be enrolled in the investigation. Subject will reside in the
GTA at time of inclusion to increase the likelihood of return for reassessment. Subjects
will be English-speaking to allow for ease of follow-up assessment. Subjects will be
reassessed at 6, 12 and 24 months after treatment for routine clinical and radiographic
follow-up. Sample wastage (subjects lost to follow-up) in a two year prospective
longitudinal pulp outcome study has been demonstrated to be approximately 50 per cent
at this institution.9,13,14 Numbers of subjects and individuals excluded from the
investigation (did not meet inclusion criteria, refused to participate, lost to follow-up) will
be recorded.
! 153!
Data analysis
The data unit for survival analyses will be a single primary maxillary incisor from each
child to preserve the independence of the observations. For subjects with multiple treated
incisors, one incisor will be selected for inclusion by random draw. Treated incisors will
be compared to each other for survival and presence of a number of clearly defined
radiographic and clinical signs. Surviving teeth will be categorized and tabulated
according to clinical and radiographic signs. Radiographic analysis of treated teeth will
be subjected to blinded assessment by independent expert raters. Their assessments will
be subjected to measures of inter-rater and intra-rater reliability. Outcome measures will
be statistically compared. The generalized estimating equation will be employed due to
the lack of independence of the observations for statistical comparisons of clinical and
radiographic outcomes.
References
1. Aminabadi NA, Farahani RM, Gajan EB: A clinical study of formocresol pulpotomy
versus root canal therapy of vital primary incisors. J Clin Pediatr Dent. 2008; 32(3): 211-
4
2. Primosch R, Glomb T, Jerrell R: Primary tooth pulp therapy as taught in pediatric
dental programs in the United States. Pediatr Dent 1997; 19:118-122
3. Hunter ML, Hunter B: Vital pulpotomy in the primary dentition: Attitudes and
practices of specialists in pediatric dentistry practising in the United Kingdom. Int J
Paediatr Dent 2003; 13:246-50
! 154!
4. Judd PL, Kenny DJ: Formocresol concerns: A review. J Can Dent Assoc 1987; 53:401-
404
5. Myers DR, Shoaf HK, Dirksen TR, Pashley DH, Whitford GM, Reynolds KE:
Distribution of 14C- formaldehyde after pulpotomy with formocresol. J Am Dent Assoc
1978; 96:805-13
6. Pashley EL, Myers DR, Pashley DH, Whitford GM: Systemic distribution of 14C-
formaldehyde from formocresol-treated pulpotomy sites. J Dent Res 1980; 59:602-7
7. Bolt HM: Experimental toxicology of formaldehyde. J Cancer Res Clin Oncology
1987; 113:305-309
8. International Agency for Research on Cancer, World Health Organization, Press
Release No.153, June 15, 2004; http://www.iarc.fr/pageroot/PRELEASES/pr153a.html
9. Casas, MJ, Kenny DH, Judd PL, Layug MA: Outcomes of vital primary incisor ferric
sulfate pulpotomy and root canal therapy. J Can Dent Assoc. 2004; 70 (1): 34-38
10. Torabinejad M, Hong CU, McDonald F, Pitt Ford, TR: Physical and chemical
properties of a new root-end filling material. J Endod 1995; 21: 349-353
11. Mitchell PJC, Pitt Ford TR, Torabinejad M, McDonald F: Osteoblast biocompatibility
of mineral trioxide aggregate. Biomaterials 1999; 20: 167-73
12. Eidelman E, Holan G, Fuks A: Mineral trioxide aggregate vs. formocresol in
pulpotomized primary molars: a preliminary report. Pediatr Dent 2001; 23: 15-84.
13. Doyle T, Casas MJ, Kenny DJ, Judd PL: MTA produces superior outcomes in vital
primary molar pulpotomy. Pediatr Dent, 2010 Jan-Feb, 32: 41-47
14. Casas MJ, Kenny DJ, Johnston, DH, Judd, PL: Long-term outcomes of primary molar
ferric sulfate pulpotomy and root canal therapy. Pediatr Dent 2004; 26:44-8
! 155!
2.11.2. Research consent form
Consent form version August 5, 2010 Page 1 of 4
Title of Research Project: A prospective outcome investigation of mineral trioxide aggregate pulpotomy in primary maxillary incisors Investigator(s): Dr. Peter L Judd, Dentist-in-Chief 416-813-6008 Dr. Michael J. Casas, Director of Clinics 416-813-6018 Dr. Ed Barrett, Staff Pediatric Dentist 416-813-8220 Purpose of the Research: This research investigation looks at the effectiveness of an alternative to our standard root canal technique for upper front teeth. Each technique is designed to eliminate the widespread use of formaldehyde (a known hazardous chemical) products in children. We demonstrated previously the effectiveness of this alternative root canal technique in children’s back (molars) teeth. This alternative technique uses a material that promotes nerve healing, is technically less demanding and requires less treatment time than our standard root canal technique. A root canal procedure will only be performed if it is required and the tooth is restorable. If the tooth is not restorable or it is infected the tooth will require extraction. Description of the Research: Approximately 160 children will participate in the study; eighty case subjects and eighty control subjects. The child’s health record will be viewed for research purposes. Your dentist will decide on the need for root canal treatment based upon the amount of decay in your child's front teeth. This will be decided after your child is asleep.
1. If your child’s tooth decay is mild, root canal treatment will not be needed and your child will not be suitable for this trial.
2. If tooth decay is too severe, extraction will be needed and your child will not be suitable for this study.
3. If the decay is moderate, root canal treatment is needed because decay has reached the nerve.
Two methods of root canal treatment are being compared in this study: 1. mineral trioxide aggregate (MTA) root canal treatment 2. zinc oxide and eugenol root canal treatment (a standard SickKids technique)
The dentist will randomly (like a toss of a coin) select from the two choices for the treatment that your child will receive. All front teeth treated in this study will be examined at follow-up visits and x-rayed at the 6, 12 and 24 month anniversaries of your child’s treatment date or until they are ready to fall out naturally. This is the routine schedule that we following for all root canal treated teeth.
! 156!
Consent/ Form Version Date: August 5, 2010
2
Potential Harms: We know of no harm that taking part in this study could cause your child. However, no root canal technique is successful in all cases and occasionally a tooth may need to be extracted. Although MTA has been shown to be an effective technique in the molar teeth, it is possible that it will not be as effective as the standard of care.
Potential Discomforts or Inconvenience: There are no anticipated discomforts associated with either technique that is not within the normal experience of root canal therapy in children. Although most children do not experience any discomfort, minor pain medication (e.g. Tempra) may be required within the first day or two following treatment. Potential Benefits: We anticipate that this alternate root canal techniqe will be as effective as the standard method based on our recently completed study using this technique on children’s molars. This study demonstrated superior results to the standard root canal technique when used in back teeth. Furthermore, this technique takes less time which means reduced treatment time in the dental chair or time spent under a general anesthetic. If this technique produces similar results in treating the front teeth, then this may become the new standard of care. To individual subjects: You (your child) will not benefit directly from participating in this study other than the possibility of a better successful outcome than the standard root canal technique. Results of the research study will be available should you be interested. To society: Dentists are more likely to use this alternative technique which is technically less demanding, less expensive and requires less treatment time (important in treating young children) and helps to eliminate the widespread use of formaldehyde (a known hazardous chemical) products in children. Alternatives to participation: As discussed at your child’s consultation appointment, alternative treatments at Sick Kids are zinc oxide-eugenol root canal treatment (one of the treatments in this study) or ferric sulfate root canal treatment or extraction, which is acceptable therapy for teeth with decay that reaches the nerve. Confidentiality: We will respect your privacy. No information about who you are (your child is) will be given to anyone or be published without your permission, unless the law requires us to do this. For example, the law requires us to give information about you (your child) if a child has been abused, if you (your child) has an illness that could spread to others, if you or someone else talks about suicide (killing themselves), or if the court orders us to give them the study papers. Sick Kids Clinical Research Monitors may see your child’s health record to check on the study.
! 157!
Consent/ Form Version Date: August 5, 2010
3
By signing this consent form, you agree to let these people look at your child’s records. We will put a copy of this research consent form in your child’s patient health records. We will give you a copy for your files. The data produced from this study will be stored in a secure, locked location. Only members of the research team (and maybe those individuals described above) will have access to the data. This could include external research team members. Following completion of the research study, the data will be kept as long as required and then destroyed as required by Sick Kids policy. Published study results will not reveal your identity.
Reimbursement:
We will reimburse you $10.00 for each recall visit to defray your costs of transportation to the hospital and in recognition of your time and effort. Participation: If you choose to let your child participate in this study, you can take your child out of the study at any time. The care your child gets at Sick Kids will not be affected in any way by whether you take part in this study.
New information that we get while we are doing this study may affect your decision to take part in this study. If this happens, we will tell you about this new information. And we will ask you again if you still want to be in the study. In some situations, the study doctor may decide to stop the study. This could happen even if the treatment given in the study is helping your child. If this happens, the study doctor will talk to you about what will happen next.
If your child becomes ill or are harmed because of study participation, we will treat your child for free. Your signing this consent form does not interfere with your legal rights in any way. The study staff, any people who gave money for the study, or the hospital are still responsible, legally and professionally, for what they do. Conflict of Interest: Dr. Peter Judd and the other research team members, have no conflict of interest to declare. Sponsorship: Dr. Peter Judd and the Department of Dentistry at the Hospital for Sick Children are the sponsor and funder of this research study.
! 158!
Consent/ Form Version Date: August 5, 2010
4
Consent: By signing this form, I agree that: 1) You have explained this study to me. You have answered all my questions. 2) You have explained the possible harms and benefits (if any) of this study. 3) I know what I could do instead of having my child take part in this study. I understand that I
have the right to refuse to let my child take part in the study. I also have the right to take my child out of the study at any time. My decision about my child taking part in the study will not affect my child’s health care at Sick Kids.
4) I am free now, and in the future, to ask questions about the study. 5) I have been told that my child’s medical records will be kept private except as described to me. 6) I understand that no information about my child will be given to anyone or be published without first asking my permission. 7) I have read and understood pages 1 to 4 of this consent form. I agree, or consent, that my child___________________ may take part in this study. 8) If I have any questions I can call Dr. Peter Judd at 416-813-6008. _________________________________ Printed Name of Parent/Legal Guardian Parent/Legal Guardian’s signature & date _________ _________________________________ Printed Name of person who explained consent Signature & date _______________________________________ __________________________________ Printed Witness’ name (if the parent/legal guardian Witness’ signature & date does not read English) If you have any questions about this study, please call _________________at__________________ If you have questions about your rights as a subject in a study or injuries during a study, please call the Research Ethics Manager at 416-813-5718.
! 159!
2.11.3. Procedural data collection form
DATA CAPTURE FORM
Patient sticker here
For SickKids dental staff use only Circle teeth treated and code the pulp technique used (bold) as defined:
MTA/FS: MTA pulpotomy with FS ZOE/RCT: Zinc oxide and eugenol root canal treatment
2. Submit this form to Dr. Peter Judd upon completion of treatment
52 51 61 62
! 160!
DATE:(!
(CLINICAL(EVALUATION(DATA(FORM(
((Tooth(#((((((((((((((((((((((((((((((((((((((((((((((((((((52( ((((((((((((51(((((((((((61(((((62(((Is(the(tooth(present?( (If#no,#explain#(ie#exfoliated,#lost#to#trauma#or#extracted)##
!!!!!!!!!!Yes!
!No!
!
(Is(the(restoration(intact?(If#no,#explain#(ie#recurrent#caries,#missing#or#mobile#restoration)##
!!!!!!!!!!Yes!
!No!
!!
(Is(there(erythema,(swelling(or(a(fistula?(If#yes,#which#one#and#explain.##
!!!!!!!!!!Yes!
!No!
!!
(Is(there(pathological(tooth(mobility?(If#yes,#explain.##
!!!!!!!!!!None!!!!!!!M1!!!!!!!M2!!!!!!!!M3!
!!
(Is(there(percussion(sensitivity?(If#yes#or#can't#tell,#explain.#(
!!!!!!!!!!Yes!
!No!
!
(Is(there(palpation(sensitivity?(If#yes#or#can't#tell,#explain.##
!!!!!!!!!!Yes!
!No!
!
(Is(there(a(history(of(pain?(If#yes#or#can't#tell,#explain.##
!!!!!!!!!!Yes!
!No!
!
(Is(there(a(history(of(swelling?(If#yes#or#can't#tell,#explain.#(
!!!!!!!!!!Yes!
!No!
!
!
2.11.4. Clinical data collection form
! 161!
2.11.5. Radiographic data collection form
! 162!
2.11.6. Ethics approval
!
PROTOCOL REFERENCE # 29065
June 6, 2013
Dr. Peter JuddFACULTY OF DENTISTRY
Dr. Trang NguyenFACULTY OF DENTISTRY
Dear Dr. Judd and Dr. Trang Nguyen,
Re: Administrative Approval of your research protocol entitled, "A prospective outcome investigationof mineral trioxide aggregate pulpotomy in primary maxillary incisors"
We are writing to advise you that the Office of Research Ethics (ORE) has granted administrativeapproval to the above-named research protocol. The level of approval is based on the following role(s)of the University of Toronto (University), as you have identified with your submission and administeredunder the terms and conditions of the affiliation agreement between the University and the associatedTAHSN hospital:
Graduate Student research - hospital-based onlyStorage or analysis of De-identified Personal Information (data)
This approval does not substitute for ethics approval, which has been obtained from your hospitalResearch Ethics Board (REB). Please note that you do not need to submit Annual Renewals, StudyCompletion Reports or Amendments to the ORE unless the involvement of the University changes sothat ethics review is required. Please contact the ORE to determine whether a particular change to theUniversity's involvement requires ethics review.
Best wishes for the successful completion of your research.
Yours sincerely,
Daniel GyewuREB Manager
OFFICE OF RESEARCH ETHICSMcMurrich Building, 12 Queen's Park Crescent West, 2nd Floor, Toronto, ON M5S 1S8 CanadaTel: +1 416 946-3273 Fax: +1 416 946-5763 [email protected] http://www.research.utoronto.ca/for-researchers-administrators/ethics/
