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Medicationandtoothmovement
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American Journal of Pharmacy and Pharmacology 2014; x(x): xx-xx
Published online MM DD 2014 (http://www.aascit.org/journal/ajpp)
Keywords
Drugs,
Orthodontic Tooth Movement,
Systematic Review
Received: September 24, 2014
Revised: October 09, 2014
Accepted: October 10, 2014
Medication and tooth movement
Nezar Watted1, *
, Peter Proff2, Borbély Péter
3,
Abu-Hussein Muhamad4
1Department of Orthodontics, Arab American University, Jenin, Palestine 2Department of Orthodontics, University of Regensburg, Regensburg, Germany 3Fogszabályozási Stúdió, Budapest, Hungary 4Department of Pediatric Dentistry, University of Athens, Athens, Greece
Email address
[email protected] (N. Watted)
Citation
Nezar Watted, Peter Proff, Borbély Péter, Abu-Hussein Muhamad. Medication and Tooth
Movement. American Journal of Pharmacy and Pharmacology. Vol. x, No. x, 2014, pp. x-x.
Abstract
Orthodontic tooth movement is basically a biologic response towards a mechanical force.
Osteoclast and osteoblast cells mediate bone resorption and apposition, which eventually
produces tooth movement. Researches showed that the rate of orthodontic tooth
movement can be altered by certain drugs locally or systemically. The Objective of this
article is to discuss the current data concerning the effect of drugs on orthodontic tooth
movement.
1. Introduction
Orthodontics is a specialty, using biomechanical principles of physiological
mechanisms that can correct dental malposition and malformations of the jaws to restore
a functional and aesthetic dentition. Orthodontic treatments are limited to dental
displacements, using either fixed or removable systems. Only the alveolar bone needs to
be remodeled. Dentofacial orthopedics treatments also include the control and
modification of jaw positions and facial growth by controlling the growth sites in the
maxilla and mandible.{1,2}
When a force is applied to the crown of a tooth, it is transmitted through the root of
the tooth to the periodontal ligament and alveolar bone. According to the direction of the
force, there will be areas of pressure and areas of tension on these supporting
structures{1}. For the tooth to move, there must be resorption of alveolar bone in
response to this stress, and if the tooth is to remain firmly attached there must also be
deposition of bone to maintain the integrity of the attachmentmechanism. In effect, the
socket of the tooth must move, concomitant with movement of the tooth through the
alveolar bone. Although the general nature of the cellular reactions to force on the teeth,
which result in bone resorption and deposition, are not in dispute, the intermediary
causes of these reactions have been the subject of morerecent investigation. The classical
theory of tooth movement suggests that the cellular reactions are simply the result of
differential pressuresinduced in the periodontal ligament, and that the response to force
is confined to the cellular elements of the ligament and the endosteal marrow spaces. {1,
2, 3}(Fig. 1, Fig. 2)
This concept has been challenged by several investigators; Baumrind has suggested
that the ligament should be considered as a continuous hydrostatic system, in which
differential pressures cannot exist. If this is so, the pressure-tension concept of the
classical theory must be questioned. {4.5, 6}
The effects of physical distortion of the alveolar bone by the forces from orthodontic
appliances may be responsible for the cellular reactions observed. Picton, Cochran et al.,
Baumrind and Grimm, among others, have shown that even relatively light forces on the
2 Nezar Watted et al.: Medication and Tooth Movement
teeth, such as are used in orthodontic treatment, cause
bending of the alveolar bone. It has also been shown that
bone which is deformed by stress becomes electrically
charged, concave surfaces taking a negative polarity and
convex surfaces a positive polarity.[6,7,8,9,10,11}
Fig. 1. Orthodontic tooth movement
Fig. 2. The biology of tooth movement17
As a result of these bioelectric potential differences, bone
is added to the concave surfaces and resorbed from the
convex surfaces. In the dento-alveolar complex this would
result in tooth movement.
Justus and Luft have put forward a mechano-chemical
hypothesis for the remodelling of bone under stress. Their
experiments have suggested that altered physical stress in the
bone changes the solubility of the hydroxyapatite crystals,
which in turn induces the osteoblastic and osteoclastic
activity which results in bone remodelling.{12,13}
Davidovitch et al. have also shown a biochemical process
resulting from mechanically stressed alveolar bone to be an
intermediate stage in bone resorption and tooth
movement.{14}
Gianelli confirmed, from experimental work, the previous
findings of several investigators that an intact vascular
perfusion system in the periodontal ligament seems to be
necessary for frontal resorption of the bone, and that when
American Journal of Pharmacy and Pharmacology 2014; x(x): xx-xx 3
the vessels are occluded by the force, undermining resorption
occurs. He put forward the suggestion that the vasculature
may act as a hydraulic pressure system, transmitting the
applied force to the attachment apparatus, the resultant
pressures distorting the crystal structure of the bone.{15}
Mostafa et al. have postulated that force applied to a tooth
produces two main effects, the periodontal tissue injury
causing vascular responses and the bending of the alveolar
bone causing piezoelectric responses and the local production
of prostaglandins, all of which mediate tooth movement.{16}
Schwarz , the ideal force is one which induces a pressure
in the periodontal ligament not exceeding capillary blood
pressure, i.e. not more than 32 mmHg. The force to be
applied by artificial means to the crown of a tooth in order to
produce such a pressure on the periodontal ligament vessels
has not been accurately assessed It is likely to depend on the
size and shape of the tooth, and particularly the size and
number of the roots. It will also be influenced by other
factors, such as the natural forces acting on the teeth and the
exact nature and direction of the force applied.{17}
The forces used in successful orthodontic treatment have
usually been determined empirically, and no doubt
sometimes cause pressures greater than capillary blood
pressure.{1,2,3,4,5,6}
In considering these forces it is necessary to review the
different types of tooth movement which are commonly
required.Table.1
Table 1. tooth movements
Several different types of tooth movement occur during
orthodontic treatment. Because of the nature of the
attachment of the teeth to the alveolar bone all these
movements are likely to be complex, but they can be
considered in simplified form as follows;
1 Tipping movements.
2 Rotational movements.
3 Bodily movements.
4 Torque movements.
5 Vertical movements
2. Force and Center of Resistance
Orthodontic appliances are used to produce force systems
that will displace teeth and initiate a biologic cascade,
allowing teeth to move. Although many treatment modalities
and philosophies advocate different appliances, the force
system they produce can be dissected into the same basic
physical components: forces and moments. Force alone can
be used to move teeth and will often produce moment
causing the teeth to also rotate, tip, and torque. By using
appliances to control rotation, practitioners gain more control
over how teeth move. Varying the ratio of moment to force
applied allows the orthodontist to vary the type of tooth
movement effected. {1}
Forces are vectors having both direction and magnitude.
To move a tooth predictably, a force needs to be applied in
the desired direction, with the desired magnitude, and at the
correct position on the tooth. Changing the direction,
magnitude, or point of force application will affect the
quality of the tooth displacement that will occur.in other
words, if mesial movement of a tooth is indicated, a force to
push or pull the tooth in a mesial direction must be
applied.{1.2}
Intuitively, the point of force application also has an
influence on the quality of the tooth movement. There is only
one point on a tooth through which a force can be applied
that will move the tooth in the direction of the force without
tipping or rotating it. This point is the center of resistence and
a force acting through it will cause pure translation of the
tooth.{1,2,5} (Fig.3, Fig. 4)
Fig. 3. Center of resistance, shown throughout as a solid black dot. A force
acting through the center of resistance results in pure translation of the tooth
Fig. 4. Center of resistance, shown throughout as a solid black dot. Center
of rotation, shown throughout as a solid red dot. A force acting not through
the center of resistance results in tipping of the tooth
4 Nezar Watted et al.: Medication and Tooth Movement
The location of center of resistance, therefore, depends on
the size and shape of the tooth as will as on the quality and
level of the supporting structures. In a healthy tooth with an
intact PDL, the center of resistance is presumed to bi
somewhere 1/3 and ½ the distance from the alveolar crest to
the root apex. For a maxillary central incisor, this is
approximately 10 mm apical to the level of placement of an
orthodontic bracket. The center of resistance is located mor
apically for a priodontally compromised tooth with loss of
attachment. {1.2.3.4} (Fig. 5, Fig. 6, Fig. 7)
Fig. 5. Center of resistance, shown throughout as a solid black dot.
Fig. 6. The center of resistance in a tooth with full periodontal support
(right). The center of resistance is more apical in periodontally compromised
tooth (left)
Fig. 7. Clinical situation, The center of resistance of the central incisor (red
dot) is different because of bone height.
3. Forces and Moment
When a force is applied at any point other than through the
center of resistence, in addition to moving the center of
resistance in the direction of the force, a moment is created.
A moment is defined as a tendency to rotate and may refer to
rotaion, tipping, or torque in orthodontic terminology (Fig. 8).
If a distal force is applied buccal to the center of resistence,
the center of resistence of the tooth will move distaly and the
tooth will rotate mesiobuccally {1}
Fig. 8. Center of resistance, shown throughout as a solid black dot. The
center of resistance of the central incisor (red dot)
4. Tipping Movements
The centre of rotation of the tooth will depend on the exact
point at which the force is applied, becoming nearer to the
apex of the root as the point of application becomes nearer to
the incisal or occlusal tip of the crown (Fig. 9, Fig. 10).
Christiansen and Burstone have shown that the amount of
force applied does not affect the position of the centre of
rotation {18}. In practice, Stephens has found that with
single rooted teeth the centre of rotation is most frequently
located in the middle third of the root {19}.
Fig. 9. Tipping-uncontrolled movement : The applied force system (A). The
equivalent force system at the Center of resistance (B). The predicted tooth
movement with a center of rotation, shown throughout as a red dot, just
apical to the center of resistance (black dots) (C).
Fig. 10. Tipping-controlled movement : The applied force system (A). The
equivalent force system at the Center of resistance (B). The predicted tooth
movement with a center of rotation at the crown (C)
American Journal of Pharmacy and Pharmacology 2014; x(x): xx-xx 5
Crabb and Wilson found that forces of 0.3 N, 0.4 N and 0.5
N would produce satisfactory distal tipping movement on
permanent upper canine teeth, the degree of force not having
any material effect on the speed of movement, but the 0.5 N
force tended to give rise to more discomfort and difficulty
with the appliance {20}. Reitan found that intermittent forces
of 70-100 g (c. 0.7-1.0 N) may produce cell-free areas in the
periodontal ligament of an upper canine [21}.
Buck and Church showed that a tipping force of
approximately 0.7 N produced undermining resorption on
upper premolars {22}.
5. Rotational Movements
Rotational movements do not normally require any greater
force than tipping movements, but there is a much greater
tendency for rotational movements to relapse. This appears to
be due to the fact that although the fibres which attach the
tooth to the bone become reorganized fairly quickly during
and after tooth movement, the fibres joining the tooth to the
gingival tissue remain intact for a long time, simply
becoming distorted during tooth movement. In rotational
movements most of these gingival fibres are compressed on
one side and on the other side stretched, and this produces the
tendency for relapse{1,2} (Fig. 11a-c).
a
b
c
Fig. 11a-c. Rotational movement (a, b) and the arregement of free gingival
fibers after rotation (c).
6. Bodily Movements –Pure
Translation
The term 'bodily movement' is taken to mean the complete
translation of a tooth to a new position, all parts of the tooth
moving an equal distance.
As force can only be applied directly to the crown of the
tooth, it must be applied over a wide area of the crown, and
any tilting movements must be restricted, if bodily movement
is to be achieved. Furthermore, for bodily movement to occur,
a restraining force must be applied to prevent tilting of the
tooth. When a force to move a tooth is applied at bracket that
is 10 mm away from the center of resistance, a tendency for
the tooth to tip is created that is 10 times the magnitude of
the force. To counteract the tendency for tipping, a couple
can be applied intentionally to produce a moment of equal
magnitude in the opposite direction. The force alone would
cause the tooth to move in the direction of the force and the
crown to tip in the same direction. The couple completely
negates this tendency to tip, but the tooth still moves in the
direction of the force. When the applied moment forces
greater than the tip forces, the tooth will translate in the
direction of the force without tipping. In pure translation, the
center of rotation is considered to be at infinity because no
rotation occurs.{1,2,3,4} ( Fig 12)
Fig. 12. Translation movement : The applied force system (A). The
equivalent force system at the Center of resistance (B). The predicted tooth
movement (C). The pure translation, the center of rotation at infinity.
For these reasons the actual force applied to the crown is
usually greater for bodily movements than for tipping
movements.
Forces of up to approximately 3.0 N have been reported as
being successful for bodily movement of upper and lower
canines, the actual amount of force depending, of course, on
the size of the root.{1}
Nikolai has found that bodily movement of a tooth
requires two to three times the force needed for simple
tipping of the same tooth, and Quinn and Yoshikawa have
reported that forces of 1.0 N-2.0 N give satisfactory bodily
movement of upper canine teeth.{23,24}
7. Torque Movements
The term 'torque' in orthodontic practice is taken to mean
6 Nezar Watted et al.: Medication and Tooth Movement
the differential movement of one part of a tooth, physically
restraining any movement of other parts.
In this sense it is the opposite of the tipping movement, in
which the crown is moved, with little movement of the root.
However, as it is not possible to apply direct force to the root
of the tooth, root torque is more difficult to achieve than
crown movement (Fig. 13, Fig 14).
Fig. 13
Fig. 14
Fig. 13, 14. Controlled root movement- torque, : The applied force system
(A). The equivalent force system at the Center of resistance (B). The
predicted tooth movement with a center of rotation at the crown (C)
At the same time, it is easier to restrain movement of the
crown than of the root, and therefore it is theoretically
possible to achieve greater differential root movement. The
main limitations to root torque lie in the size and form of the
bone of the jaw, as the root movement must be confined to
the available supporting bone.
For practical purposes the forces are generally applied over
an area of the crown rather than at single points, this giving
greater control over the movements. Shows that the pressure
on the supporting structures is greatest in the apical area, and
the apex of the root moves further than any other part of the
tooth. There is a greater risk of apical resorption with this
type of movement than with any other type if the forces are
not carefully controlled, and the forces required should not be
as great as for bodily movement, though they will be greater
than for tipping movements because of the necessity of
applying an opposing force to restrict movement of the
crown. Reitan reported that a force of approximately 0.5 N is
favourable for to rquing movement of upper first premolars.
{1, 2, 3, 4, 22, 23|
8. Vertical Movements
Vertical movements are essentially bodily movements, but
are considered separately because they are easier to produce
and involve different types of pressure on the supporting
structures.
Extrusion of the tooth from its socket can be achieved
without much resorption of bone, bone deposition being
required to re-form the supporting mechanism of the tooth
(Fig. 15a, b) Generally speaking, tension is induced on the
whole of the supporting structures, rather than pressure
Intrusion of the tooth involves resorption of bone,
particularly around the apex of the tooth.{1,2,3,4,9,17,22,23}
(Fig. 16a-d).
a
b
Fig. 15a, b. Extrusion of an intruded tooth
a
b
American Journal of Pharmacy and Pharmacology 2014; x(x): xx-xx 7
c
d
Fig. 16a-d. Intrusion of an extruded tooth (a, b, c). Bone Remodeling (d)
In this movement the whole of the supporting structures
are under pressure, with virtually no areas of tension.
Vertical movements of teeth need the application of force
over a wide area of the crown, being difficult to bring about
with force applied only to one point. As no counteracting
forces are required, forces of the same order as, or less than,
those used for tipping movements are sufficient, and, because
of the direction of tooth movement, excessive forces are
likely to damage the blood vessels entering the dental pulp at
the apex, with subsequent death of the tooth. Resorption of
the root apices is another potential hazard, particularly with
intrusive forces. Dermaut and De Munck have reported
considerable root shortening after intrusion of upper
incisors{25}. Reitan found that a force of approximately 0.25
N was sufficient for the extrusion of an individual tooth{26},
and Burstone found a similar force suitable for intrusion of
an incisor{27}.
9. Multiple Tooth Movement
Orthodontic treatment frequently involves the application
of force to move a number of teeth simultaneously. In these
circumstances, the total force applied will often exceed the
figures previously quoted for individual tooth movement,
because the force will be spread over several teeth (Fig 11b).
Orthodontists often prescribe drugs to manage pain from
force application to biological tissues, manage
temporomandibular joint problems and tackle fungal and
viral infections throughout the course of treatment. A recent
review of pharmaceuticals commonly used in orthodontic
practice, provided an insight into the dosage,
pharmacological actions and side effects of these agents.
A part from these drugs, patients who consume vitamins,
minerals, and other compounds, for the prevention or
treatment of various diseases, can also be found in every
orthodontic practice. Some of these drugs may have profound
effects on the short and long term outcomes of orthodontic
treatment. However, in manycases little is known on the
nature of this interaction between specific drugs and
orthodontic tissue remodeling, thereby increasing the risk of
negative effects.{1,2,3,4,17}
Orthodontic treatment is based on the biologic principle
that prolonged pressure on teeth results in remodelling of
periodontal structures, allowing for tooth movement[1]. The
bony response is mediated by the periodontal ligament.
Within a few hours after force application, a change in the
chemical environment produces a cascade of cellular events.
There is an increased level of cAMP, prostaglandin E and
interleukin-1 beta levels. Other chemical messengers like
cytokines, nitric oxide and other regulators of cellular
activity are also involved. Since drugs of various types can
affect both prostaglandin levels and other potential chemical
messengers, pharmacologic interventions may modify the
response to orthodontic force.{1,2,3,4}
This information is important for clinicians in
communications with patients, because many patients use
prescription and over-the counter medications, as well as
dietary supplements daily. Consequently, these substances
can affect both the rate of orthodontics teeth movement and
the expected duration of treatment.{1,4}Table.2
Table 2. Bone Remodeling with orthodontics forces
It is possible to categories drugs that would affect
orthodontic tooth movement into the four broad categories:
non-steroidal anti-inflammatory drugs (NSAID),
8 Nezar Watted et al.: Medication and Tooth Movement
corticosteroids, other analgesics and bisphosphonates. There
are a number of systemic factors and mediators however that
could influence the rate of orthodontic tooth movement.{1,5}
10. Effect of Individual Drugs on the
Orthodontic Tooth Movement can
be summarized as
10.1. Analgesics
Analgesic is a drug that selectively relieves pain by acting
on the CNS or peripheral pain mechanisms, without
significantly altering consciousness. The analgesic action is
mainly due to obtunding of peripheral pain receptors and
prevention of PG mediated sensitization of nerve endings.
NSAIDs are a relatively weak inhibitor of PG synthesis.{3,5}
NSAID’s are the most commonly used medications in
orthodontics, for control of pain following mechanical force
application to tooth.
Recent research demonstrated the molecular mechanisms
behind the inhibition of tooth movement by NSAID’s. The
levels of Matrix Mettallo-proteinases(MMPs)-9 and
(MMPs)-2 were found to be increased, along with elevated
collagenase activity, followed by a reduction in procollagen
synthesis which are essential for bone and periodontal
remodelling. The whole process is controlled by inhibition of
COX activity, leading to altered vascular and extra vascular
matrix remodelling, causing a reduction in the pace of the
tooth movement.{5,6,7}
Acetylsalicylic acid and the related compounds: Their
action results from inhibition of cyclooxygenase activity,
which converts unsaturated fattyacids in cell membrane to
prostaglandins. Clinical experience shows that orthodontic
tooth movement is very slow in patients undergoing long-
term acetylsalicylic therapy. Salicylate therapy decreases
bone resorption by inhibition of PG synthesis and may affect
differentiation of osteoclasts from their precursors.
Therefore, it is recommended that patients undergoing
orthodontic treatment should not be advised to take aspirin &
related compounds for longer periods during orthodontic
treatment.
A recent study reported that nabumetone,a drug belonging
to NSAID group, reduces the amount of root resoption along
with control of pain from intrusive orthodontic forces without
affecting the pace of tooth movement.{1.5}Table.3
Table 3. Effects of NSAIDs on orthodontic tooth movement
Kyrkanides et al investigated the effect of indomethacin on
orthodontic tooth movement. Their results indicated loss of
prostaglandin mediated cellular effects subsequent to
cyclooxygenase inhibition by this drug.{28}
The cyclooxygenase inhibition resulted in exacerbation of
IL-1β-mediated collagenase B (MMP-9) synthesis and
activity, as well as attenuation of type IV procollagen
synthesis levels by endothelial cells. Furthermore, Ito et al(38)
reported that the induction of MMP-9 synthesis caused
cyclooxygenase inhibition in rabbit articular
chondrocytes.{29}
Chan et al reported that new COX-2 specific inhibitors
decreased serious gastrointestinal perforations, obstructions
and bleeding when compared with conventional NSAID.{30}
De Carlos et al studied orthodontic tooth movement that
resulted from the effect of rofecoxib (COX-2 inhibitor) and
compared with diclofenac (a traditional NSAID). The results
showed both rofecoxib and diclofenac can inhibit COX-2
action that means that the orthodontic tooth movement was
inhibitedby these drugs.{31}
Kyrkanides et al stated that the use of anti-inflammatory
drugs may
Influence orthodontic tooth movement by altering
biochemical pathways that mediate extracellular matrix
remodeling. At the present, the use of cyclooxygenase-2
(COX-2) inhibitor for relief orthodontic pain is increasing,
and replacing conventional NSAIDs because its anti-
inflammatory effect is less injurious to gastrointestinal
mucosa than the nonselective NSAID.{28}
Chumbley and Tuncay recommended that orthodontic
patient should avoid to using aspirin and other nonsteroidal
anti-inflammatory analgesics to relieve pain because these
drugs can prolong orthodontic treatment time{32}.
Gameiro et al reported the short- and long-term effects of
celecoxib (COX-2 inhibitor) on orthodontic tooth movement
in rats. The short-term treatment was simulated the
preoperative administration of analgesics to decrease post-
operative pain whereas the long-term effect treatment was
simulated the situation that patients receive celecoxib in
treatment of chronic
American Journal of Pharmacy and Pharmacology 2014; x(x): xx-xx 9
disease all time of tooth movement. The results showed
that tooth movement was inhibited by celecoxib action in
both situations. Moreover, they stated that celecoxib not only
affected COX-2 level but also affected IL-1 and IL-6 that had
the result of bone resorption and toothmovement.{33}
Mohammed et al foundthat orthodontic tooth movement is
inhibited by indomethacin in rats. Furthermore, Arias’s study
showed the effect of aspirin and ibuprofen on orthodontic
tooth movement in the rats. Fewer osteoclasts were observed
in the pressure side of the teeth because these drugs inhibited
the production of PGs. Because the bone resorption was
reduced, the teeth moved less than average.{34}
Sari et al suggested that the one drug, rofecoxib, can be
used to relieve pain or patient discomfort during orthodontic
treatment because the inhibitory effect on PGs synthesis with
rofecoxib was less than the inhibition effect of aspirin during
the first 24 hours.{35}
Wong et al stated that aspirin does not change the
orthodontic tooth movement in guinea pigs. However, they
found that the dose of the analgesic used was lower than the
dose that can reduce the secretion of PGs because the
metabolic rate of these animals is faster than humans. For
this reason, they require higher doses than the does to
produce the same orthodontic effect in humans.{36}
Williams etal studied the effect of ibuprofen on alveolar
bone in dogs. Their result showed that ibuprofen can inhibit
alveolar bone loss when the dogs were treated with 4 mg/kg
of ibuprofen daily for 13 months. {37}
Kehoe et al confirmed that ibuprofen inhibits PGE2
synthesis in the PDL of guinea pig significantly by
decreasing the degree and rate of orthodontic tooth
movement.{38}
10.2. Acetaminophen
Paracetamol (acetaminophen) was first identified in the
late nineteenth century and it was available in the UK on
prescription in 1956, and over-the-counter in 1963. Since
then, it has become one of the most popular antipyretic and
analgesic drugs worldwide, and it is often also used in
combination with other drugs. The lack of a significant anti-
inflammatory activity of paracetamol implies a mode of
action which is distinct from that of the non-steroidal anti-
inflammatory drugs. Yet, the Cochrane Systematic Review,
2004 concluded that paracetamol was effective against the
postoperative pain in adults.{1.5,28}
Acetominophen (paracetamol) a weak COX-1 and COX-2
inhibitor that also reduces urinary prostaglandin levels after
systemic administration, has shown no effect on orthodontic
tooth movement in quinea pigs and rabbits. Comparative
studies and our clinical experience have demonstrated that
acetaminophen is effective for controlling pain and
discomfort associated with orthodontic treatment.{5,28,38}
Kehoe et al found that at the level of PDL, acetaminophen
inhibited the peripheral PGs synthesis but the degree and rate
of orthodontic tooth movement were not significantly
different when compared with control group.{38}
Arias et al showed the presence of osteoclasts in the
pressure side of the orthodontically moved incisors in rats
treated with acetaminophen. The bone resorption lacunae and
dental movement are the same as the control group.
Furthermore, the bone is actively regenerated because of
orthodontic treatment that activates the secretion of PGs and
the osteoclasts that act in bone resorption. These results did
not happen in the groups treated with aspirin and
ibuprofen.{39}
Roche claimed that acetaminophen has no effect on
orthodontic tooth movement in rabbits because
acetaminophen is a weak inhibitor of cyclooxygenase-1 and
cyclooxygenase-2, and analgesic action lacks the anti-
inflammatory properties.{40}
Piroxicam is an oxicam derivative (enolic acid) that
inhibits COX-1 and COX-2 and it has antiinflammatory,
analgesic, and antipyretic activities. It is a nonselective COX
inhibitor. Approximately 20% of the patients experience side
effects with piroxicam, and about 5% of the patients
discontinue its use because of these effects {41}
Tenoxicam, a long acting analgesic has been in use for a
long time, with good patient compliance, as it only needs to
be used once a day because of its long elimination half-life. It
has shown good results in controlling acute pain of mild or
moderate intensity, such as the pain which is triggered by an
orthodontic activation, without the presentation of any
significant adverse effects.{42}
In 1997, Roche JJ et al reported that acetaminophen
showed no effect on tooth movement when tested on rats.
Generally, studies suggests that paracetamol does not affect
orthodontic tooth movement, so it’s safe to use as a choice of
pain management in orthodontic treatment.{40}
As orthodontic tooth movement is considered to involve an
inflammation process, many studies regarding the effect of
anti-inflammatory drugs on tooth movement and root
resorption have been reported. However, controversy still
exists. The purpose of the present investigation is to provide
a quantitative assessment of the effect of steroidal and
nonsteroidal anti-inflammatory drugs on tooth movement and
root resorption by using scanning electron and laser
microscopes.{5,7,40,41,42}
10.3. Vitamin D
Vitamin D and its active metabolite, 1,25,2(OH)D3,
together with parathyroid hormone (PTH) and calcitonin,
regulate the amount of calcium and phosphorus levels.
Vitamin D receptors have been demonstrated not only in
osteoblasts but also in osteoclast precursors and in active
osteoclasts{43}. In 1988, Collins and Sinclair demonstrated
that intraligamentary injections of vitamin D metabolite,
1,25-dihydroxy cholecalciferol, caused increase in the
number of osteoclasts and amount of tooth movement during
canine retraction with light forces{44}. In 2004, Kale and
colleagues observed that local applications of vitamins
enhanced the rate of tooth movement in rats due to the well-
balanced bone turnover induced by vitamin D.{45} Brandi
and colleagues reported that rats treated with vitamin D
showed increased bone formation on the pressure side of the
10 Nezar Watted et al.: Medication and Tooth Movement
periodontal ligament after application of orthodontic forces.
In 2004, Kawakami observed an increase in the mineral
appositional rate on alveolar bone after orthodontic force
application; they suggested that local application of vitamin
D could intensify the re-establishment of supporting alveolar
bone, after orthodontic treatment.{46} The effect of vitamin
D may be the same as PTH. The rate of bone resorption will
increase when vitamin D is in excess.
10.4. Bisphosphonates
Bisphosphonates (BPNs) have strong chemical affinity to
the solid-phase surface of calcium phosphate; this causes
inhibition of hydroxyapatite aggregation, dissolution, and
crystal formation. Bisphosphonates cause a rise in
intracellular calcium levels in osteoclastic-like cell line,
reduction of osteoclastic activity, prevention of osteoclastic
development from hematopoietic precursors, and production
of an osteoclast inhibitory factor. Studies have shown that
BPNs can inhibit orthodontic tooth movement and delay the
orthodontic treatment {47}. Topical application of BPNs
could be helpful in anchoring and retaining teeth under
orthodontic treatment..{4,5,6}
The study of Igarashi et al showed that after giving of
subcutaneousbisphosphonates for 3 weeks in rats, tooth
movement was decreased by 40%. In addition, the alveolar
bone adjacent to the periodontal ligament showed the
reducing of osteoclasts after giving a single dose of
intravenous bisphosphonate (pamidronate) during tooth
movement.{47,48} Marx et al stated that bisphosphonate
osteonecrosis showed the decrease of microcirculation of
bone until the stage of necrosis happened. Because the
osteoclast cannot absorb the mineral matrix of bone, and the
capillary formation in new bone cannot be stimulated
completely, acellular and avascular bone will occur.) The
typical osteonecrosis in patients who received intravenous
bisphosphonate appeared as painful abscess teeth. When they
are extracted, the underlying necrosis bone will be exposed,
and abnormal healing causes bone loss in the future. {49}
At the present, there should be concerned about
orthodontic treatment in the patients who received
bisphosphonates High intravenous doses of bisphosphonates
can inhibit tooth movement more than lower oral doses.
Orthodontic tooth movement may increase the uptake of
bisphosphonates locally, so it decreases osteoclastic activity.
The result of this process shows as slower
toothmovement.{5,7,18.47,48,49}
10.5. Fluorides
Fluoride is one of the trace elements having an effect on
tissue metabolism. Fluoride increases bone mass and mineral
density, and because of these skeletal actions, it has been
used in the treatment of metabolic bone disease, osteoporosis.
Even a very active caries treatment with sodium fluoride
during orthodontic treatment may delay orthodontic tooth
movement and increase the time of orthodontic treatment.
Sodium fluoride has been shown to inhibit the osteoclastic
activity and reduce the number of active osteoclasts. {50}
10.6. Corticosteroids
These drugs are used as anti inflammatory and
immunosuppressive agent in treatment of a wide range of
chronic medical conditions. a low dose(1mg/kg body
weight)decreases orthodontic tooth movement by
suppressing osteoclastic activity. At high dose (15mg/kg
body weight)it increases osteoclastic activity thus produces
more rapid orthodontic tooth movement and subsequent
relapse.[51]
The main effect of corticosteroid on bone tissue is direct
inhibition of osteoblastic function and thus the decrease of
total bone formation.{51} Decrease in bone formation is due
to elevated parathyroid hormone levels caused by inhibition
of intestinal calcium absorption which are induced by
corticosteroids. Corticosteroids increase the rate of tooth
movement, and since new bone formation can be difficult in
treated patient, they decrease the stability of tooth movement
and stability of orthodontic treatment in general.{51,52}
When they are used for longer periods of time, the main
side effect is osteoporosis. It has been demonstrated in
animals with this type of osteoporosis that the rate of active
tooth movement is greater, but tooth movement is less stable
since little bone is present and no indication of bone
formation. A more extensive retention may be required.{52}
Corticosteroids acts by preventing the formation of
prostaglandins by influencing the arachidonic acid pathway.
An endogenous protein, lipocortin formed by steroids acts by
blocking the activity of phospholipase A2, thus inhibits the
release of arachidonic acid which in return influences the
synthesis of prostaglandin, leukotrienes or thromboxanes.
Corticosteroids also act by reducing the release of
lymphokines, serotonin and bradykinin at the injured site[25].
They play a vital role in inhibiting the intestinal calcium
absorption, which leads to direct inhibition of osteoblastic
function, and increase in bone resorption.{51,52,53}
Kalia and colleagues[26] evaluated the rate of tooth
movement in rats during short and long term corticosteroid
therapy. They concluded that bone remodeling seemed to
slow down in acute administrations, whereas the rate of tooth
movement increased in chronic treatment. This suggest that
orthodontic treatment should be postponed in patient
undergoing short term corticosteroids whereas, patient with
long term corticosteroid therapy treatment can be continued
with minimal adverse effect and more extensive retention
may be helpful in retaining these teeth if the dentist decides
to proceed with the orthodontic treatment.{54}
When they are used for longer periods of time, the main
side effect is osteoporosis. It has been demonstrated in
animal models with this type of osteoporosis that the rate of
active tooth movement is greater, but tooth movement is less
stable since little bone is present and there is no indication of
bone formation. A more extensive retention may be
required.{52,53,54}
American Journal of Pharmacy and Pharmacology 2014; x(x): xx-xx 11
10.7. Thyroid Hormones
Thyroid hormones are recommended for the treatment of
hypothyroidism and used after thyroidectomy in substitutive
therapy. Thyroxin administration lead to increased bone
remodeling, increased bone resorptive activity, and reduced
bone density. Effects on bone tissue may be related to the
augmentation of interleukin-1 (IL-1B) production that
thyroid hormones induce at low concentrations, cytokine
stimulate osteoclast formation and osteoclastic bone
resorption.
The speed of orthodontic tooth movement increased in
patients undergoing such medication. Low-dosage and short-
term thyroxin administrations are reported to lower the
frequency of “force induced” root resorption. Decrease in
resorption may be correlated to a change in bone remodeling
process and a reinforcement of the protection of the
cementum and dentin to “force induced” osteoclastic
resorption {55}
Calcitonin has the opposite effects. It is a peptide hormone
secreted by the thyroid, which decreses the intestinal calcium
and renal calcium reabsorption. In bones, calcitonin
inactivates osteoclasts and hence inhibits bone résorption. It
also stimulates the bone forming activity of
osteoblasts.{5,7,55} The thyroid hormone increases the speed of orthodontic
tooth movement in patients undergoing such medication. Low
dosage and short-term thyroxine administration are reported
to lower the frequency of "force-induced" root resorption.
Decrease in resorption may be correlated to a change in bone
remodeling process and a reinforcement of the protection of
the cementum and dentin to "force-induced" osteoclastic
resorption{55}
10.8. Sex Hormones
Sex hormones play a role of bone metabolism. Estrogen
has a direct effect on bone. It preserves calcium in bone by
suppressing the activation frequency of bone remodeling.
The remodeling activation will increase when menopause
starts and the result is rapid bone loss leading to symptomatic
osteoporosis.
Estrogen directly stimulates the bone-forming activity of
osteoblasts, so it is reasonably to expect a slower rate of
orthodontic tooth movement.[56]
Androgens also inhibit bone resorption and modulate the
growth of the muscular system. Thus, the excessive use of
these drugs by athletes, in an attempt to achieve better
athletic scores, may affect the duration and results of the
orthodontic treatment[,57,56].
10.9. Parathyroid Hormone
The function of parathyroid is to maintain a normal level
of diffuse calcium and phosphorus in the blood plasma and to
keep constant the ratio of these minerals to each other. The
act as a check on the thyroid gland parathyroids are important
organs in ca metabolism and play a leading role in
calcification of teeth. However, once the teeth are formed,
there is no evidence found of calcium withdrawal from teeth
due to parathyroid disturbances. The parathyroids are
important in regulating blood ca level, but have little or no
direct effect on growth or tooth eruption.{5,7}
PTH affects osteoblasts’ cellular metabolic activity, gene
transcriptional activity, and multiple protease secretion. Its
effects on osteoclasts occur through the production of
RANK-L Recepor activator of nuclear factor kappa -B
ligand), a protein playing a crucial role in osteoclasts’
formation and activity. In 1970s, animal studies demonstrated
that PTH could induce an increase in bone turnover that
would accelerate orthodontic tooth movement. More recently,
an increased rate of tooth movements has been observed in
rats treated with PTH, whether administered systemically or
locally. These results indicate that orthodontists should take
note of patients being treated with PTH, as for example, in
cases of severe osteoporosis.{57}
Parathyroid hormone affects both bone resorption and
formation process. If PTH appears around bone cells, the
effect of bone will be resorption. By contrast, low level of
PTH results in bone formation. When the calcium level in
blood decreases, PTH will stimulate osteoclastic activity to
increase calcium and phosphate absorption in the gut, and
decrease calcium excretion and tubular phosphate
reabsorption in the kidney. This plays a role as regulator of
calcium homeostasis by PTH.{57,58}
10.10. Anti Convulsants
Valporic acid has a potential to induce gingival bleeding
even with minor trauma making orthodontic maneuvers
difficult. Phenytoin induces gingival hyperplasia due
overgrowth of gingival collagen fibers, which involves the
interdental papilla, making application of orthodontic
mechanics difficult and difficulty in maintaining oral hygiene.
Gabapentin produce xerostomia, making oral hygiene
maintenance difficult during orthodontic treatment. In these
cases, clinician should be aware of possible difficulties
during treatment period, and discuss it with the patients and
or parents and educate them so that adequate measures to
maintain oral hygiene are followed.{59}
10.11. Alcohol
Chronic ingestion of large amounts on daily basis may
have devastating effects on a number of tissue systems,
including skeletal system. Alcoholism may lead to severe
complications, such as liver cirrhosis, neuropathies,
osteoporosis, and spontaneous bone fractures. Circulating
ethanol inhibits the hydroxylation of vitamin D3 in liver, thus
impending calcium homeostasis. In such cases the synthesis
of PTH is increased, tipping the balance of cellular function
towards the enhanced resorption of mineralized tissues,
including root resorption in order to maintain normal levels
of calcium in blood. It was found that chronic alcoholics
receiving orthodontic treatment are high risk of developing
severe root resorption during course of orthodontic
treatment.{60}
12 Nezar Watted et al.: Medication and Tooth Movement
Davidovitch et al. have found that chronic alcoholics
receiving orthodontic treatment are at high risk of developing
severe root resorption during course of orthodontic
treatment.{60,61}
10.12. Prostaglandins and Analogs
Experiments have shown that PGs may be mediators of
mechanical stress during orthodontic tooth movement. They
stimulate bone resorption, root resorption, decrease collagen
synthesis, and increase cAMP. They stimulate bone
resorption by increasing the number of osteoclasts and
activating already existing osteoclasts. A lower concentration
of PGE2 (0.1 μg) appears to be effective in enhancing tooth
movement. Higher concentration leads to root resorption.
Systemic administration is reported to have better effect than
local administration. Researchers have injected PGs locally at
the site of orthodontic tooth movement to enhance the bone
remodeling process and the pace of tooth movement. The
main side effect associated with local injection of PGs is
hyperalgesia due to the release of noxious agents.{61}
Yamasaki et al found an increased number of osteoclasts in
rats alveolar bone after local injection of PGEI. A similar
regimen in human subjects increased significantly the rate of
canine and premolar movement.{62}
PGs act by increasing the number of osteoclasts, and by
promoting the formation of ruffled borders, thereby
stimulating bone resorption. Among the PGs that had been
found to affect bone metabolism (E1, E2, A1, and F2-alpha),
PGE2 stimulated osteoblastic cell differentiation and new
bone formation, coupling bone resorption in vitro.This
indicates that although they enhance the tooth movement
process, their side effects are very serious to consider its
clinical use. Recent trends are directed toward combining
local anesthetics with PGs, in order to reduce pain while
injected locally. Research in this regard is still in its
preliminary phase.{63,64}
For prostaglandin mediated bone resorption process,
intracellular calcium is essential. Furthermore, IL-1 can
stimulate prostaglandins as a potent stimulator of bone
resorption.PGE1 and PGE2 are found to increase bone
resorption. But PGI2 inhibits osteoclastic activity and
stimulates bone formation.{63,64,65}
11. Insulin
Insulin is a polypeptide hormone secreted by the beta cells
of the Langerhans islets of the pancreas. A normal non-obese
man secretes approximately 50U/day, with a basal plasma
insulin concentration of 10-50 microns/ml. Its main function
is to maintain the blood glucose level. Insulin deficiency
produces a clinical state called diabetes mellitus, while its
excess leads to hypoglycemia. Diabetes mellitus is diagnosed
in 3-4% of the population treated in our day-to-day
orthodontic practice. The orthodontic practitioner should
have a basic knowledge and understanding of this disease
and of its impact on the oral cavity, as well as of its
consequences upon the dental treatment.{66}
Informed on the oral complications induced by diabetes
mellitus, the dental practitioner should consider them when
treating a DM patient; the key to any orthodontic treatment is
a good medical control. No orthodontic treatment should be
performed in a patient with uncontrolled diabetes. There is no
treatment reference with regard to fixed or removable
appliances.{67}
A good oral hygiene is especially important when fixed
appliances are used, as they may increase plaque retention,
which could more easily cause tooth decay and periodontal
breakdown. Daily rinses with fluoride-rich mouthwash can
provide further preventive benefits. Candida infections may
also occur in the oral cavity, so that they should be well
monitored. Diabetes related microangiopathy can
occasionally appear in the periapical vascular supply,
resulting in unexplained odontalgia, percussion sensitivity,
pulpitis, or even loss of vitality in sound teeth. Especially in
orthodontic treatments involving force application for
moving teeth over a considerable distance, the practitioner
should regularly check the vitality of the teeth involved. It
isadvisable to apply light forces and not to overload the
teeth .{66}
Holtgrave and Donath, who studied the periodontal
reaction to orthodontic forces, evidenced retarded osseous
regeneration, weakening of the periodontal fibers and
microangiopathies in the gingival areas. In adults, before
starting the orthodontic treatment, the orthodontist should
obtain a full-mouth (periodontal) examination and evaluation
of the need for periodontal treatment.
The periodontal condition should be improved before
staring the treatment and should be monitored regularly.
Maintaining a strict oral hygiene is important, by a proper
use of toothbrush, interdental toothbrush and chlorhexidine
mouthwash.{67,68}
To minimize the neutralizing effect of toothpaste on the
chlorhexidine molecule, an at least 30-min interval should be
left between tooth brushing and chlorhexidine rinse As no
upper age limit for orthodontic treatments is any longer valid
today, the practitioner will see both type1 and type2 DM
patients. Type2 patients can be considered more stable than
type1 ones, as hypoglycemic reactions are more frequent in
these patients. If a patient is scheduled for a long treatment
session, he or she should be advised to eat a usual meal and
take the medication as usual.{66.67} At each appointment,
the orthodontist should confirm the meal and medication, to
avoid a hypoglycemic reaction in the office. DM patients
with good metabolic control, without local factors, such as
calculus, and with a good oral hygiene, have a similar
gingival status as the healthy ones, consequently they can be
treated orthodontically.{66,67,68}
11.1. Anaesthetic Gels
Anaesthetic gels are safer alternatives to analgesics in
reducing the pain which results from orthodontic procedures.
Keim et al., in their study, stated that they may be of use
when orthodontic procedures are performed, such as band
placement and cementation, archwire ligation, and
American Journal of Pharmacy and Pharmacology 2014; x(x): xx-xx 13
band/bracket removal. The advantage of this system is its
delivery method, which simply introduces the gel into the
gingival crevice and makes it entirely painless.{69}
11.2. Cytokines
Cytokines are small proteins that are identified as
mediators of bone resorption. One cytokine, Interferon
(IFN)-γ, acts as a bone resorption inhibitor that is opposite to
other cytokines.
Leukotrienes are a type of eicosanoid which is a product of
arachidonic acid conversion and are the only eicosanoids that
are formed independently from cyclooxygenase (COX). They
are produced when arachidonic acid is metabolised by
lipoxygenase enzymes[19].Leukotrienes also play an
important role in Inflammation, allergies, and diseases such
as asthma. These conditions can be cured by using
leukotriene inhibitors which block leukotriene receptors
hence counteracts their effects. Examples of medication are
montelukast and zafirlukast. According to Mohammed AH et
al. , leukotrienes causes increase in orthodontic tooth
movement, through bone remodeling whereas, leukotrine
inhibitors work the other way round. Therefore, the use of
leukotriene inhibitors can delay orthodontic treatment,
leukotrienes can be used in future clinical applications that
could result in increasing tooth movement.{34}
Interleukin (IL)-1 has potential as a bone resorption
stimulator by stimulation of prostaglandins. From
experimental studies, applying tensile stress to periosteal
fibroblasts will increase the level of IL-1 inhibitor. IL-1 has
two molecular forms, alpha (IL-1∝)and beta (IL-1β), and is
secreted by many kinds of cells such as macrophages, B cells,
neutrophils, fibroblasts, and epithelial cells. IL-1 and
prostaglandins are synergistic.{70}
Interleukin (IL)-2 shows in the attraction and proliferation
of osteoclast progenitors as well as the stimulation of acid
production by osteoclasts.{70,71)
Interleukin (IL)-6 is produced by lymphocytes,monocytes
and fibroblasts.(11) It is one of an inflammatory cytokines
that stimulates plasma cell proliferation and antibody
production. Furthermore, this cytokine stimulates osteoclast
and bone resorption.{5,.72,73}
Interleukin (IL)-11 stimulates osteoclast formation and
bone resorption. The effect of osteoclast formation may be
prostaglandins mediated.{72,73}
Tumor necrosis factor (TNF) and lymphotoxin are
cytokines that are implicated in the stimulation of
osteoclastic bone resorption. This effect is produced by
prostaglandins mediation.{71,72,73}
Interferon (IFN)-γ is produced by activated T lymphocytes.
It can inhibit bone resorption by inhibiting the differentiation
of precursors into mature cells.{71}
Leukotriene B4 (LTB4) has a highly potential as a
chemotactic agent. It induces the accumulation of
inflammatory cells especially neutrophils and stimulates bone
resorption.{72,73}
11.3. Cyclosporine
It increases gingival hyperplasia. In most patients the
greatest changes in the gingival occurs in first six months of
cyclosporine therapy. Severe gingival hyperplasia, make
orthodontic treatment, and maintenance of oral hygiene
difficult. Treatment should be started or resumed after
surgical removal of excessive gingival tissues once there is
good oral hygiene. Whenever possible, fixed appliances
should be kept to a minimum period with brackets, and
avoiding the user of cemented bands. Removable appliances
in these cases are not recommended, due to improper fit.{5,7}
11.4. Anti-Histamines
Histamine (H(1)) receptor antagonists are widely used
drugs for treatment of allergic conditions. Although
histamine was shown drugs may have varying effects on
orthodontic tooth movement.{66,67,72}
11.5. Growth Factors
Bone morphogenetic proteins (BMPS) are stored in the
osteoblasts and bone. They are the important factors that can
initiate osteoblastogenesis.
Fibroblast growth factor (FGF) is secreted by macrophages,
osteoblasts and stored in bone. It has a direct effect to
stimulate osteoblast proliferation.{72}
Transforming growth factor (TGF)-β is stored in bone and
secreted by osteoblasts, macrophages and PDL cells. It can
stimulate formation of bone by involving the cartilaginous
intermediate and induce granulation tissue formation. TGF-β
was found on the tension side of tooth movement and plays a
negative role for osteoclastogenesis.{72}
Platelet-derived growth factor (PDGF) is secreted by PDL
cells, macrophages, endothelial cells, and osteoblasts, and
stored in bone. It has biologic effects of mitogenesis and
chemotaxis on osteoblasts and fibroblasts. PDGF can
promote skin healing, bone formation and periodontal
regeneration,
Insulin-like growth factor (IGF) is secreted by PDL cells,
macrophages, osteoblasts, plasma cells and stored in bone as
well as TGF- β. It is an important mediator of postnatal
longitudinal growth. Normally, IGF alone can not
significantly stimulate bone healing, but it can work together
with platelet-derived growth factor (PDGF) for enhancing
bone healing process. So, IGF is synergistic with PDGF and
stimulates extracellular matrix.
11.6. Relaxin
Relaxin has been known for decades as a pregnancy
hormone. It is released just before child birth to loosen the
pubic symphysis, so that the relaxed suture will allow
widening of the birth canal for parturition. It has also been
shown to have effects on a multitude of other physiological
processes, including the regulation of vasotonus, plasma
osmolality, angiogenesis, collagen turnover, and renal
function.{77}
14 Nezar Watted et al.: Medication and Tooth Movement
Relaxin’s influence on soft tissue remodeling and on
several mediators that stimulate osteoclast formation have
attracted attention from orthodontics researchers.{77,78}
11.7. EP4 Agonist
Bone anabolic responses to external loading areinduced by
stimulation of prostaglandin receptor EP4.
Chung et al claimed that the activation of the EP4 receptor
of the paradental region might induce osteoblasts and
stimulate new bone formation in vivo. Their study reported
that the local administration of EP4 agonist can induce tooth
movement and increase bone volume at least in the tension
side. Furthermore, PGE stimulates bone resorption through
the EP4 receptor via a mechanism involving an increase of
cAMP and RANKL in osteoblasts. So, there is a high
possibility of increased bone resorption.{77,79}
Chung et al stated that the role of EP4 agonists not only
enhances bone formation during tooth movement but also
stimulate osteoblasts to produce increased amounts of
RANKL that increase osteoclastogenesis and bone
resorption.{79}
12. Discussion
This systematic review of literature summarizes the effects
of medications, such as anti-inflammatory and anti-asthmatic ,
anti-arthritics, analgesics, corticosteroids, estrogens and other
hormones, and calcium regulators in orthodontic tooth
movement. As described by Krishnan V and Davidovitch Z,
these groups of drug have an effect on OTM. Some of these
drugs are promoter drugs where it promotes orthodontic tooth
movement, but others have an inhibitory effect{70,71}.
Orthodontic tooth movement is accompanied by bone
remodeling (alveolar bone turnover). The remodeling of bone
is a cycle that starts with activation followed by resorption,
reversal and formation phases.
The activation period is about 10 days. There are cells
recruitment, differentiation, proliferation and migration in
this period followed by resorption. The resorption period
takes 21 days that occurs by osteoclast activity.{70}
The next stage is reversal stage when inactive osteoblasts
become activated and begin to form bone. Bone formation is
determined by rate and duration of osteoblast activity.
The new bone formation is completed over a period of 6
months with mineralization. The remodeling cycle from
activation through to the start of the formation phase requires
about 4 months in humans. The amount of bone remodeling
is related to the amount of tooth movement at that site.{70,71}
Davidovitch et al.and Yamasaki et al.[concluded in their
study that the rate of orthodontic tooth movement can be
altered by administrating certain drugs locally or systemically.
The drugs used in orthodontics can be broadly classified into
two major groups, promoter drugs and suppressor agents.
Promoter drugs are agents that act with the secondary and
primary inflammatory mediators and enhance the tooth
movement, examples being; Prostaglandin, Leukotrienes,
Cytokines, Vitamin D, Osteocalcin, and Corticosteroids.
Suppressor agents are drugs which reduces bone resorption
examples are; Nonsteroidal anti-inflammatory agents and
bisphosphonates.{62,63,64,70,71}
As a clinician, this information is very important because
orthodontic treatment does involve postoperative pain and
the form of pain management is very important because not
all drugs favours tooth movement. Many patients use over
the counter medications for immediate pain relief, which may
interfere with the treatment plan. Therefore, practitioners
should have a proper knowledge of the drugs being
prescribed and the patient should be well
informed.{5,6,7,62,70}
During orthodontic tooth movement, bone remodeling
process is related to the expression of mediators. Acute
inflammatory response is presented in the early phase of
orthodontic tooth movement. Inflammatory mediators may
stimulate the biological processes that associated with
alveolar bone resorption and deposition. Furthermore,
orthodontic forces can induce the bone remodeling process
by the local mediators, such as prostaglandins, cytokines and
growth factors, that play an important role in bone
remodeling. PGE2 has been involved in bone remodeling and
especially recognized as a potent stimulator of bone
resorption.{62,63,64}
There are several studies showing the usage of
pharmacologic agents to induce bone resorption and
deposition for control of tooth movement. For example, the
study of Yamasaki shows the usage of local injection of
prostaglandin to stimulate tooth movement.Other
pharmacologic agents such as calcitonin, and
1,25(OH)2D3can also induce tooth movement. The daily
injection of osteocalcininto the palatal subperiosteum in rat
showed it can stimulate tooth movement significantly in the
early period but not significantly after day 5th.One injection
of 1,25(OH)2D3 per 7 days into the PDL of cats increased
tooth movement 60% as well as in the human that received
PGE1 submucosal injection. Although the pharmacologic
agents can induce the tooth movement in both human and
animal study but they have side effects during the injection
procedure such as local pain and discomfort, so these
techniques are not practical to use for the patient.{5}
Role of vitamin D3 and Corticosteroids in still orthodontic
tooth movement{5,61,62,63} remains unclear. Some author
have reported that it promotes tooth movement but there are
also studies that demonstrate bone formation after application
of these drugs. So, it is important to have more clinical trials
on determining the exact role of Vitamin D3 and
Corticosteroids in orthodontic tooth movement.{61.62,63}
Bisphosphonates are drugs which also effect the calcium
homeostasis. It is known for its role in inhibiting tooth
movement. They are used in cases of prevention of
orthodontic relapse but it should be used with great caution
because of its severe side effects on long term use.{47.48}
Eicosanoids such as prostaglandins and leukotrienes are
group of drugs, which increases the rate of orthodontic tooth
movement.
They act by stimulating bone resorption. Eicosanoid
American Journal of Pharmacy and Pharmacology 2014; x(x): xx-xx 15
inhibitors on the other hand acts in preventing OTM.
Example of eicosanoid inhibitors are NSAIDs where it
inhibits the synthesis of prostanoids which is an important
mediator of bone resorption. So, it is important that the
patient does not take NSAIDs such as aspirin or other related
compounds for long periods of time during orthodontic
treatment[55]. The alternative that can be suggested to
patients is paracetamols. Paracetamol also known as
acetaminophen is a type of analgesic, which does not have
any deleterious effect on orthodontic tooth movement.
Hormones also play an important role in tooth movement.
Hormones such as thyroxin is known to increase the rate of
tooth movement by directly stimulating the actionof
osteoclast.Calcitonin and estrogen have the opposite effect on
tooth movement. It is very important to know if the patient is
under any oral contraceptive pills. It contains estrogens,
which inhibits tooth movement.{5,7,8,23}
NSAIDs such as Ibuprofen and aspirin can inhibit
orthodontic tooth movement. They reduce the synthesis of PGs
that results in decreasing osteoclasts in the pressure sides.
Because they have potential for slowing tooth movement, it is
not recommended to use them for relief of orthodontic pain.
Nowadays, the numbers of adult orthodontic patients are
increased, so orthodontists for long-term treatment for chronic
diseases such as arthritis, tricyclic antidepressants, and
antiarrhythmics that can experience reduced rate of tooth
movement. COX-2 inhibitor reduce the osteoclast activity and
inhibit tooth movement as well as NSAIDs.{28,30}
Orthodontists should be aware of the patients who under
short- and long- term therapy with COX-2 inhibitors because
these drugs can decrease the rate of orthodontic tooth
movement. Acetaminophen acts at the central nervous system
and does not stimulate PGs synthesis, so it does not interfere
with the orthodontic tooth movement. The numbers of
osteoclasts in the pressure areas are not decreased, and the
bone regeneration does not change by acetaminophen.So, it is
a drug of choice that orthodontists should recommend to their
patients for relieving the discomfort during orthodontic
treatment.{5,7,33,36,61,62,63}
Bisphosphonate is used in patients who have bone
metabolism disorders. It can inhibit tooth movement.
Furthermore, it impairs bone healing and induces
osteonecrosis in alveolar bones of maxilla and mandible.
Medication screening and patient counseling are essential in
these patients.{47,48,49}
13. Conclusion
As more and more chemical analogues are being used in
the form of new drugs to avoid resistance, today’s clinicians
should mandatorily update his knowledge on the clinical
efficacy of the new drugs as well as the beneficial and
harmful effects on human tissues . It is always advisable for a
dentist to confirm with the family physician or the concerned
physician for fitness of the patients who under go
orthodontics involving tooth movement.
Orthodontists should assume that many patients are taking
prescription or over-the counter medications regularly. The
orthodontist must identify these patients by carefully
questioning them about their medication history and their
consumption of food supplements and it should consider a
part of every orthodontic diagnosis.
References
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