Lack of Clinical Evidence on Low-level Laser Therapy (LLLT) on Dental Titanium Implant a Systematic...

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REVIEWARTICLE

Lack of clinical evidence on low-level laser therapy (LLLT)on dental titanium implant: a systematic review

J. C. Prados-Frutos1 & J. Rodríguez-Molinero1& M. Prados-Privado1

& J. H. Torres2 &

R. Rojo1

Received: 7 October 2015 /Accepted: 28 December 2015 / Published online: 11 January 2016# Springer-Verlag London 2016

Abstract Low-level laser therapy (LLLT) has proved to have

biostimulating effects on tissues over which they are applied,therefore accelerating the healing process. Most studies in

implantology were focused on a reduction of the duration of

osseointegration. There exist few articles analyzing the poten-

tial effects of these therapies on the osseointegration of titani-

um dental implants. The aim of this study was to assess the

effect of LLLT on the interaction between the bone and the

titanium dental implant and the methodological quality of the

studies. We conducted an electronic search in PubMed, ISI

Web, and Cochrane Library. From 37 references obtained,

only 14 articles met the inclusion criteria. The analysis of

the studies shows that most of the experiments were per-

formed in animals, which have a high risk of bias from the

methodological point of view. Only two studies were conduct-

ed in human bone under different conditions. Several proto-

cols for the use of low-power laser and different types of laser

for all studies analyzed were used. Although animal studies

have shown a positive effect on osseointegration of titanium

implants, it can be concluded that it is necessary to improve

and define a unique protocol to offer a more conclusive result

by meta-analysis.

Keywords Low-level laser therapy . Dental implants .

Osseointegration . Regeneration . Bone remodeling .Biological processes

Introduction

Early scientific research with laser in dentistry was carried

out at the beginning of the 1960s and went on until the

1980s. However, it was not until the 1990s that the Food

and Drug Administration (FDA, USA) approved for the

first time the use of laser, Nd-YAG in this particular case,

for the surgery of soft tissues in the oral cavity. Numerous

advances have been made since then, and they have led to

the generalization of the use of laser, either high- or low-

power ones, in the different fields of dentistry for treat-

ment such as of oral mucositis [1], tooth sensitivity [2],

osteonecrosis [3], or alveolar osteitis [4] pain in orthodon-

tic treatment [5]. Low-power laser has proved to have

biostimulating effects on tissues over which it is applied,

t h e r ef o r e a c c e le r a t i ng t h e h e a l in g p r o c es s . I n

implantology, most studies were focused on a reduction

of the duration of osseointegration [6, 7].

Technical background

Lasers may be classified in multiple ways, regarding their

active medium, their wavelength, their emission patterns,

or other criteria. It is usual to classify them taking into

account the power at which they are going to be used.

Therefore, two main groups of lasers can be considered:

high-power lasers and low-power lasers [8].

Low-level lasers are those that emit within the red

spectrum or the near-infrared region with an average

J. C. Prados-Frutos and R. Rojo contributed equally to this work.

* R. Rojo

[email protected]

1 Department of Stomatology, Rey Juan Carlos University, Avenida de

Atenas, s/n, 28922 Alcorcón, Madrid, Spain

2 Department of Oral Surgery, Faculty of Odontology, University of

Montpellier 1, Montpellier, France

Lasers Med Sci (2016) 31:383 – 392

DOI 10.1007/s10103-015-1860-0

http://crossmark.crossref.org/dialog/?doi=10.1007/s10103-015-1860-0&domain=pdf



power from 50 mW to 1 W. Since their action is mainly

based on photochemical effects, they have the distinctive

property of not raising tissue temperature.

The most common kinds of low-power lasers are (1)

gallium arsenide (GaAs) laser (pulsed laser with a

wavelength of 904 nm), (2) fiber optic-transmissible

gallium and aluminum arsenide (GaAlAs) laser (with a

wavelength of 830 nm), and (3) helium – neon (HeNe)laser (with a wavelength of 632.8 nm), the latter emit-

ting within the visible spectrum, specifically the red

one.

Since they lack thermal effect, low-energy lasers are

not generally used in surgery. Indeed, their power is

lower and the area of effect is larger than that in the

high-energy ones. Therefore, the heat is dispersed and

may not result in alterations of the bone tissue. Never-

theless, they are mainly used because of their cell bio-

stimulating, analgesic, and anti-inflammatory actions.

Currently, they are mainly applied to accelerate tissue

regeneration and wound healing while reducing inflam-mation and pain [9]. Also, they are frequently used to

treat dentin hyperesthesia and to act as an antibacterial

disinfecting method in endodontic and periodontal treat-

ments [10].

Biostimulating effects of low-level laser therapy

Early works regarding the use of low-level laser therapy

(LLLT), which describe its biostimulating effects, were

carried out at the end of the 1960s and the beginning of

the 1970s, and their main goal was to observe an ac-

celeration of the healing process in the treatment of

chronic ulcers. Their results showed the efficiency of

this new kind of therapy, which could generate a possi-

ble biostimulating effect on wound healing. Despite the

lack of knowledge about LLLT-specific mechanisms, the

authors thought that these good results were due to an

increase in both epithelial and fibroblast proliferation

and stimulation of collagen synthesis and phagocytic

activity, as well as of endorphin induction [11].

The proposed theories invoked a possible increase in cell

proliferation due to the influence of photoreceptors in the cel-

lular respiration chain and stimulation of the immune

response.

The mechanisms through which the photobiostimulation

generated by LLLT is produced still remain unclear [12]. It

has been suggested that laser radiation promotes cellular redox

activity, which plays a vital role in cell regulation since its

modification participates in the modulation of many biologi-

cal processes.

Through angiogenesis stimulation, LLLT has proven its

ability to improve bone mineral density of the regenerated

bone in distraction osteogenesis cases. This constitutes the

phenomenon of photobiomodulation [13], a mechanism

that has also been invoked in the case of treatment with

allogenic bone graft for bone deficit clinical situations

previously to implant treatment [14].

Also, and by the same mechanism, de Souza et al. [15]

and Barbosa et al. [16] showed the positive effect of

LLLT on bone repair. This effect, which depends on theduration of application and the wavelength, led to a sig-

nificant decrease in the time required to achieve bone

remodeling.

The effects of low-level laser therapy

on the osseointegration of dental implants

An objective of dental implant therapy is to achieve an

appropriate union between the patient ’s alveolar bone and

the implant, which is known as osseointegration [17].

This step is likely to occur in the shortest time possible.

Many treatments have been proposed aiming to im-

prove and accelera te bone formation around the dental

implant surface. As in the other disciplines of dentistry,

LLLT has also been applied on the field of implantology

[18].

There exist few articles analyzing the potential effects

of these new therapies, especially those of LLLT on the

osseointegration of implants. Hence, the aim of this sys-

tematic review was to update this topic from the results

obtained after the review of scientific literature, in order

to understand in a more detailed way the effects of LLLTon the interaction between the bone and the implant, as

well as to evaluate its possible influence in the duration of

osseointegration and any other relevant circumstances re-

garding implantology.

Material and methods

We prepared this systematic review by following the Preferred

Reporting Items for Systematic Reviews and Meta-Analyses

(PRISMA) checklist [19].

Inclusion and exclusion criteria

We included articles that were published from January

2000 to 2015, were published in any language, and were

in vitro and in vivo studies (with any animal model) that

evaluate the effect of LLLT on the osseointegration of

titanium implants. The articles that were not included

were observational studies, systematic reviews, and liter-

ature reviews.

384 Lasers Med Sci (2016) 31:383 – 392



Search strategy

A computerized literature search was performed by two inves-

tigators (JR and RR) using PubMed/MEDLINE, Cochrane

Library, and ISI Web. Table 1 shows the search strategy.

Article selection

Two authors (RR and JR) performed all searches and selected

articles fulfilling the inclusion criteria independently and in

duplicate. Any article that does not clearly meet the criteria

after review of the full text was decided by a third author (JC-

PF) (Fig. 1). The level of agreement between the reviewers

regarding study inclusion was calculated using Cohen’s kappa

statistic.

Assessment of risk of bias and methodological quality

The assessment of risk of bias from clinical studies in humanswas evaluated by JR and RR following the Cochrane Hand-

book [20]. The assessment of risk of bias in clinical studies in

animal models was evaluated by JR and RR based on the

study of Krauth et al. [21] and with the following list of

criteria:

Table 1 Search strategyPubMed/MEDLINE BLaser Therapy, Low-Level^ [MeSH] AND BDental Implants^ [MeSH] AND

((Btitanium implant ̂ [title/abstract]) OR (Osseointegration [MeSH]) OR (osseo*

[title/abstract]))

ISI Web (BLow-Level Laser Therapy^ AND BDental Implant*^) AND Osseointegration

Cochrane Library ID Search

#1 BLow level laser therapy^

#2 BOsseointegration^

#3 #1 and #2

#4 Bdental implants^

#5 #1 and #4

Fig. 1 Flow chart

Lasers Med Sci (2016) 31:383 – 392 385



T a b l e 2

S t u d y c h a r a c t e r i s t i c s

A u t h o r

( y e a r )

M o d e l

o f s t u d y

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i n t e r v a l s

L a s e r t y p e

D o s e , p o i n t s o f a p p l i c a t i o n

n u m b e r

D a y s o f

l a s e r

a p p l i c a t i o n

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i m p l a n t

a n d s u r f a c e

P e r f o r m e d a n a l y s i s

R e s u

l t s

G a r c í a -

M o r a l e s

e t a l .

[ 2 3 ]

( 2 0 1 2 )

H u m a n s n =

8

1 2 w

e e k s

G a A

l A s

W a v e l e n g t h =

8 3 0 n m a n d

8 6 m

W ; 2

0 p o i n t s

( 3 s / p o i n t o f


) × 0 . 2 5 J ;

t o t a l e n e r g y

d e n s i t y = 9

2 . 1 J / c m 2

E v e r y

4 8 h

f o r 1 4 d a y s

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X i V

E - S

( D e n t s p l y F r

i a d e n t ® )

R e s o n a n c e

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t a b i l i t y v a l u e s

i n c r e a s e d i n

t h e

i r r a d i a t e d g r o u p

f r o m d a y

1 0

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i t h n o s t a t i s t i c a l

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n i f i c a n c e

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t a b i l i t y v a l u e s

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i r r a d i a t e d g r o u p

d e c r e a s e d

f r o

m d a y 1 0 u n t i l w e e k

6

M a n d i ć

e t a l .

[ 2 4 ]

( 2 0 1 5 )

H u m a n s n =

1 2

6 w e e k s

G a A

l A s


6 3 7 n m a n d

4 0 m

W ; t o

t a l e n e r g y

d e n s i t y = 6

. 2 6 J / c m 2

E v e r y

2 4 h

f o r 7 d a y s

B l u e S k y ®

( B r e d e n t ,

G e

r m a n y )

I m p l a n t ø 4 m m

a n d h e i g h t 1 0 m m

R e s o n a n c e

f r e q u e n c y

a n a l y s i s

( 1 ) I r

r a d i a t e d i m p l a n t s a c h i e v e d a

h i g h e r s t a b i l i t y c o m p a r e d w

i t h

c o

n t r o l s d u r i n g t h e e n t i r e

f o l l o w

- u p a n d t h e

d i f f e r e n c e

r e a c h e d s i g n i f i c a n c e

i n t h e

5 t h

p o

s t o p e r a t i v e w e e k

( 2 ) T

h e d i f f e r e n c e i n A L P

a c t i v i t y

b e t w e e n t h e g r o u p s

w a s

i n s i g n i f i c a n t

D ö r t b u d a k

e t a l . [ 7 ]

( 2 0 0 2 )

B a b o o n s n =

5

5 d a y s

D i o d e l a s e r

W a v e l e n g t h o

f 6 9 0 n m a n d

1 0 0 m

W ; 1 p o i n t

( 1 m

i n / p o i n t o f


) ; d o s e =

6 J

1 d a y

I m p l a n t ø =

5 . 5

m m ;

h e i g h t = 1 0 m

m ;

a c i d - e t c h e d , s a n d b l a s t e d

s u r f a c e

H i s t o l o g i c a l s t u d y

( 1 ) H

i g h e r o s t e o c y t e v i a b i l i t y

i n

t h e

l a s e r - t r e a t e d g r o u p a

( 2 ) S

i m i l a r r e s o r p t i o n a r e a

i n t h e

l a s e r a n d c o n t r o l g r o u p s

K h a d r a

e t a l .

[ 2 5 ]

( 2 0 0 4 )

R a b b i t s

n =

1 2

8 w e e k s

G a A

l A s


8 3 0 n m a n d

1 5 0 m

W ; 9 p o i n t s ×

3 J /

s e s s i o n ( 2 0

s / p o i n t o f


) ; e n e r g y

d e n s i t y p e r p o i n t o f


= 2 3 J / c m 2

1 0 c o n s e c u -

t i v e d a y s

C y l i n d r i c a l ø =

6 . 2 5 m m ;

h e i g h t = 1 . 9 5

m m

T i O

2 -

b l a s t e d s u r f a c e

( 1 ) T e n s i l e t e s t

( 2 ) H i s t o m o r p h o m e t r i c

e v a l u a t i o n

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X -

r a y m

i c r o a n a l y s i s

( 1 ) H

i g h e r b o n e a n c h o r a g e

i n t h e


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l a s e r -

t r e

a t e d g r o u p a

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p h

o s p h o r u s % i n t h e

l a s e r -

t r e

a t e d g r o u p a

L o p e s

e t a l .

[ 2 6 ]

( 2 0 0 5 )

R a b b i t s

n =

1 4

1 5 , 3

0 ,

a n d

4 5

d a y s D i o d e l a s e r


8 3 0 n m a n d

1 0 m

W ; 4

p o i n t s ×

2 1 J /

c m 2 ; t o t a l e n e r g y

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5 J / c m 2

E v e r y

4 8 h

f o r 1 5 d a y s

C y l i n d r i c a l ø =

2 . 6 m m ;

h e i g h t = 6 m m

R a m a n s p e c t r o s c o p y

( 1 ) N

o d i f f e r e n c e i n H A

c o n c e n t r a t i o n

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l a s e r - t r e a t e d g r o u p a n d t h e

c o

n t r o l g r o u p a f t e r

1 5 d a y s

( 2 ) H

i g h e r a m o u n t o f

H A i n t h e

l a s e r - t r e a t e d g r o u p a f t e r

3 0

a n d 4 5 d a y s a

K i m e t a l .

[ 2 7 ]

( 2 0 0 7 )

R a t s

n =

2 0

1 , 3 , 7 , 1 4 ,

a n d

2 1

d a y s G a A

l A s


8 0 8 n m a n d

9 6 m

W ; 6

p o i n t s o f


( 1 0 s / p o i n t

o f a p p l i c a t

i o n ) ; t o t a l

e n e r g y p e r

s e s s i o n = 6

. 7 2 J

E v e r y

2 4 h

f o r 7 d a y s

I m p l a n t ø =

2 m

m ;

h e i g h t = 3 . 5 m m ; t h r e a d

s i z e o f

0 . 4 m

m

( 1 ) I m m u n o h i s t o c h e m

i c a l

a n a l y s i s

( 2 ) H i s t o m o r p h o m e t r i c

a n a l y s i s

( 1 ) R

A N K L :

h i g h e r e x p r e s s i o n

i n

t h e l a s e r - t r e a t e d g r o u p t h a n

i n

t h e c o n t r o l g r o u p

f r o m d a y

1 ,

b e i n g i t s e x p r e s s i o n

i n b o n e

m o r e e v i d e n t o n

d a y s 1 4 a n d

2 1 ( 2 ) O

P G :

h i g h e r e x p r e s s i o n

i n

t h e

l a s e r - t r e a t e d g r o u p t h a n

i n

386 Lasers Med Sci (2016) 31:383 – 392



T a b l e 2

( c o n t i n u e d )

A u t h o r

( y e a r )

M o d e l

o f s t u d y

S i z e

s a m p l e

S t u d y

i n t e r v a l s

L a s e r t y p e


n u m b e r

D a y s o f

l a s e r


T y p e o f

i m p l a n t

a n d s u r f a c e


R e s u

l t s

t h e c o n t r o l g r o u p

i n e v e r y

d a y

o f

t h e s t u d y

( 3 ) R

A N K : s i m

i l a r e x p r e s s i o n

i n

b o

t h g r o u p s , t h o u g h t h e

c o

n t r o l g r o u p r e c o r d e d

l o w e r

v a l u e s o n

d a y 2 1

( 4 ) H

i g h e r b o n e d e n s i t y i n t h e

l a s e r - t r e a t e d g r o u p t h a n

i n t h e

c o

n t r o l g r o u p

L o p e s e t

a l . [ 2 8 ]

( 2 0 0 7 )

R a b b i t s

n =

1 4

1 5 , 3

0 ,

a n d

4 5

d a y s L a s e r

p h o t o b i o m o d u l a t i o n


8 3 0 n m

a n d 1 0 m W

; 4

p o i n t s × 2 1

. 5 J / c m 2 ;

t o t a l e n e r g y

d e n s i t y = 8

6 J / c m 2

E v e r y

4 8 h

f o r 1 5 d a y s

C y l i n d r i c a l t i t a n i u m

i m p l a n t s

( 2 . 6

m m

,

6 m m

l o n g ; D e n t F

i x ® ;

C a m

b u í , B r a z i l )

R a m a n s p e c t r o s c o p y

a n d S E M

( 1 ) D

i f f e r e n c e i n H A

c o n c e n t r a t i o n

b e t w e e n t h e

l a s e r - t r e a t e d g r o u p a n d t h e

c o

n t r o l g r o u p a f t e r

3 0 a n d

4 5

d a y s a

( 2 ) H

i g h e r a m o u n t o f

H A

J a k s e e t a l .

[ 2 9 ]

( 2 0 0 7 )

S h e e p

n =

1 2

1 6 w

e e k s

D i o d e l a s e r


6 8 0 n m

a n d 7 5 m W

( 1 ) S i n u s l i f t :

1 p o i n t

( 1 m

i n / p o i n t o f


) w

i t h a n

e n e r g y d e n

s i t y o f

3 – 4 J /

c m 2

( 2 ) S e c o n d s u r g i c a l p h a s e

( i m p l a n t s ) :

1 p o i n t

( 1 m

i n / p o i n t o f


) w

i t h a n

e n e r g y d e n

s i t y o f

3 – 4 J /

c m 2

( 1 ) S i n u s

l i f t : d a y s

1 , 3 , a n d

7 ( 3 d a y s )

( 2 ) S e c o n d

s u r g i c a l

p h a s e

( i m -

p l a n t s ) :

d a y s 1 , 3 ,

a n d 7

( 3 d a y s )

U n k n o w n

H i s t o m o r p h o m e t r i c

e v a l u a t i o n

( 1 ) S

i n u s l i f t : n o

d i f f e r e n c e s i n

b o

n e r e g e n e r a t i o n

b e t w e e n t h e

l a s e r - t r e a t e d a n d c o n t r o l

g r o u p s a f t e r

4 a n d

1 2 w e e k s

p o

s t s u r g e r y

( 2 ) S

e c o n d s u r g i c a l p h a s e

i m

p l a n t s : h i g h e r B I C % i n t h e

l a s e r - t r e a t e d g r o u p a f t e r

4 a n d

1 2

w e e k s a

P e r e i r a e t

a l . [ 3 0 ]

( 2 0 0 9 )

R a b b i t s

n =

1 2

3 a n d 6

w e e -

k s

G a A

l A s


7 8 0 n m ;

4

p o i n t s ( 1 0

s / p o i n t o f


) ; 7 . 5 J / c m 2

E v e r y

4 8 h

f o r 1 4 d a y s

C y l i n d r i c a l a n d

s e l f -

t a p p i n g ø = 3

. 3 m m a n d

h e i g h t = 6 m m


e v a l u a t i o n

( 1 ) H

i g h e r B I C % i n t h e


M a l u f e t

a l . [ 3 1 ]

( 2 0 1 0 )

R a t s

n =

2 4

1 4 d a y s

G a A

l A s


7 9 5 n m ;

4

p o i n t s ( 2 . 0

J / c m 2

b y

p o i n t ) ; t o t a

l i n g a

d o s e

o f 8 J / c m 2

/ d a y

E v e r y

4 8 h

f o r 1 2 d a y s

2 m m o f

d i a m e

t e r f o r

3 . 5 m m o f l e

n g t h

( C o n e x ã o S i s t e m a s

d e

P r ó t e s e s ,

A r u

j á , S ã o

P a u l o ,

B r a z i

l )

D i g i t a l t o r q u e m a c h i n e

( 1 ) T

h e e x p e r i m e n t a l g r o u p

p r e s e n t e d

l a r g e r d i f f i c u l t y f o r

b r e a k i n g u p t h e

i m p l a n t

i n t e r f a c e w

i t h t h e

b o n e b l o c k

t h a n t h e c o n t r o l g r o u p a

B o l d r i n i e t

a l . [ 6 ]

( 2 0 1 3 )

R a t s

n =

6 4

7 , 1 5

, 3 0 ,

a n d

4 5

d a y s G a A

l A s


8 0 8 n m

a n d 5 0 m W

; 2 p o i n t s

o f a p p l i c a t

i o n

( 1 . 2 3 m

i n / p o i n t o f


) ; e n e r g y

d e n s i t y = 1

1 J / c m 2

T w o a p p l i c a -

t i o n s f o r

1 d a y

T i t a n i u m m

i c r o

- i m p l a n t

( T i t a n i u m F i x

A . S .

T e c h n o l o g y ,

S ã o J o s é

d o s C a m p o s

, S ã o P a u l o ,

B r a z i l )

4 . 0 m

m i n l e n g t h

a n d 2 . 2 m m

i n d i a m e t e r

T o r q u i m e t e r

( 1 ) A

t 3 0 - a n d

4 5 - d a y p e r i o d s ,

t o r q u e v a l u e s t e n d e d t o

i n -

c r e a s e w

h i c h w e r e s t a t i s t i c a l l y

h i g h e r

f o r t h e

L L L T g r o u p a

Lasers Med Sci (2016) 31:383 – 392 387



T a b l e 2

( c o n t i n u e d )

A u t h o r

( y e a r )

M o d e l

o f s t u d y

S i z e

s a m p l e

S t u d y

i n t e r v a l s

L a s e r t y p e


n u m b e r

D a y s o f

l a s e r


T y p e o f

i m p l a n t

a n d s u r f a c e


R e s u

l t s

P r i m o e t

a l . [ 3 2 ]

( 2 0 1 3 )

R a t s

n =

1 2

4 5 d a y s

D i o d e l a s e r


8 3 0 n m ;

4 . 8 J / c m 2

i n 4 d i f f e r e n t

s i t e s ( 1 2 1 s )

1 d a y

1 . 4 m m

i n d i a m

e t e r a n d

3 . 3 m m

i n l e

n g t h

( P r o m m

I n d u s t t r i a

d e

M a t e r i a i s C i r u r g i c o s

L t d a .

, P o r t o

A l e g r e ,

B r a z i l )

R e m o v a l t o r q u e t e s t

( 1 ) I m

p l a n t s w

i t h a r o u g h s u r f a c e

s e e m t o a d d r e s i s t a n c e t o t h e

b o

n e – i m p l a n t

i n t e r f a c e

c o m p a r e d w

i t h s m o o t h

t i t a n i u m

i m p l a n t s o r

i m p l a n t s

t r e

a t e d w

i t h L L L T a

M a s s o t t i

e t a l .

[ 3 3 ]

( 2 0 1 5 )

R a b b i t s

n =

2 4

3 0 d a y s

G a A

l A s


8 3 0 n m a n d

5 0 m

W a t

3 d i f f e r e n t

e n e r g y d e n

s i t i e s p e r

t r e a t m e n t s e s s i o n

( E - 5 ,

5 J / c m 2 ; E - 1 0 ,

1 0 J /

c m 2 ; a n d E

- 2 0 , 2 0 J /

c m 2 )

E v e r y

4 8 h

f o r 1 3 d a y s

C o n i c a l , s e l f - t a p p i n g

o s s e o i n t e g r a t e d

i m p l a n t

( 3 . 2 5 ø ×

1 1 . 5

m m

,

N N T 3 2 1 1 ; N

a n o T i t e ;

B I O M E T 3 i , P a l m

B e a c h

G a r d e n s ,

F L ,

U S A )


e v a l u a t i o n

( 1 ) S

i g n i f i c a n t l y h i g h e r B I C a n d

s i g

n i f i c a n t l y m o r e c o l l a g e n

f i b

e r s i n g r o u p

E - 2 0 a

G o m e s e t

a l . [ 3 4 ]

( 2 0 1 5 )

R a b b i t s

n =

3 2

4 3 d a y s

G a A

l A s

8 3 0 n m

, 5 0 m

W ;

5 , 1 0 ,

a n d 2 0 J / c m

2

E v e r y

4 8 h

f o r 1 3 d a y s

3 . 2 5 m m

i n d i a

m e t e r ,

1 1 . 5 m m

( N a n o T

i t e ;

B I O M E T 3 i

, F L

, U S A )

I S Q a n d

S E M

( 1 ) T h e r e s u l t s s h o w e d

b e t t e r I S Q

f o r t h e

2 0 J / c m 2

g r o u p a

( 2 ) B

I C v a l u e s w e r e s i g n i f i c a n t l y

h i g h e r a

i n t h e

2 0 J / c m 2

g r o u p ,

o n

b o t h S E M a n d s t e r e o l o g y

( 3 ) B

o n e a r e a v a l u e s w e r e

b e t t e r

i n

t h e 1 0 J / c m 2 a

a n d 2 0 J / c m 2 a

g r o u p s c o m p a r e d t o t h e

c o

n t r o l g r o u p

B I C b o n e – i m p l a n t c o n t a c t , H A h y d r o x y a p a t i t e , R A N K r e c e p t o r a c t i v a t o r o f n u c l e a r

f a c t o r k a p p a B

, O P G o s t e o p r o t e g e r i n , R A N K L r e c e p t o r a c t i v a t o r o f n u c l e a r

f a c t o r k a p p a

B l i g a n d , A L P a l k a l i n e

p h o s p h a t a s e a c t i v i t y , L L L T l o w

- l e v e l

l a s e r t h e r a p y , I S Q i m p l a n t s t a b i l i t y q u o t i e n t ,

S E M s c a n n i n g e l e c t r o n m

i c r o s c o p y

a

S t a t i s t i c a l l y s i g n i f i c a n t r e s u l t s

388 Lasers Med Sci (2016) 31:383 – 392



Treatment allocation/randomization It describes whether or

not treatment was randomly allocated to animal subjects so

that each subject has an equal likelihood of receiving the

intervention.

Concealment of allocation It describes whether or not proce-

dures were used to protect against selection bias by ensuring

that the treatment to be allocated is not known by the investi-

gator before the subject enters the study.

Blinding It relates to whether or not the investigator in-

volved with performing the experiment, collecting data,

and/or assessing the outcome of the experiment was un-

aware of which subjects received the treatment and which

did not.

Inclusion/exclusion criteria It describes the process used for

including or excluding subjects.

Sample size calculation It describes how the total number of

animals used in the study was determined.

Compliance with animal welfare requirements It describes

whether or not the research investigators complied with ani-

mal welfare regulations.

Financial conflict of interest It describes if the investiga-

tor(s) disclosed whether or not he/she has a financial

conflict of interest.

Statistical model explained It describes whether the statis-

tical methods used and the unit of analysis are stated and

whether the statistical methods are appropriate to address

the research question.

Use of animals with comorbidity It describes whether or

not the animals used in the study have one or more

preexisting conditions that place them at greater risk of

developing the health outcome of interest or responding

differently to the intervention relative to animals without

that condition.

Test animal descriptions It describes the test animal charac-

teristics including animal species, strain, sub-strain, genetic

background, age, supplier, sex, and weight. At least one of

these characteristics must be present for this criterion to be

met.

Dose – response model It describes whether or not an appro-

priate dose – response model was used given the research ques-

tion and disease being modeled.

All animals accounted for It describes whether or not the

investigator accounts for attrition bias by providing details

about when animals were removed from the study and for

what reason they were removed.

Optimal time window investigated It describes whether or

not the investigator allowed sufficient time to pass be-

fore assessing the outcome. The optimal time windowused in animal research should reflect the time needed

to see the outcome and depends on the hypothesis being

tested. The optimal time window investigated should not

be confused with the “therapeutic time window of treat-

ment,” which is defined as the time interval after expo-

sure or onset of disease during which an intervention

can still be effectively administered.

Data extraction

Two authors (RR and JR) extracted all data from the selected

papers.

Statistical analysis

Given the heterogeneity of the dose, type of laser, and

number of applications, it was not possible to perform a

meta-analysis and data were analyzed from a descriptive

point of view. A Cohen’s kappa statistic was used to

evaluate interexaminer agreement on study eligibility

and quality using R version 3.1.3 (R Core Development

Fig. 2 Assessment of methodological quality of studies in humans

Lasers Med Sci (2016) 31:383 – 392 389



Team, R Foundation, Vienna, Austria) with the interrater

reliability (irr) package.

Results

All search strategies yielded 37 papers. Two investigators(JR and RR) independently identified 18 eligible papers.

Interexaminer agreement on study eligibility was high

(k = 0.855, p= 0.042). One author (JR) extracted all data

from the selected papers. Table 2 shows the characteris-

t ics o f th e s tu d ie s . On e s tud y wa s e x c lud e d a fte r

contacting the author because it was a book [22]. Two

studies were clinical trials on humans, and 12 were clin-

ical trials on animals.

Results of methodological quality assessment

Studies in humans by Mandić et al. [24] do not describethat patients have been randomly selected and allocated

through self-selection being a method that provides a high

risk of bias. Using the predetermined seven domains for

risk of bias assessment, we determined the study of

Mandić et al. [24] and García-Morales et al. [23] with a

Fig. 3 Assessment of methodological quality of studies in animals

390 Lasers Med Sci (2016) 31:383 – 392



high risk of bias. Figures 2 and 3 show the assessment of

risk of bias and methodological quality.

In animal studies, some authors describe the method of

treatment allocation/randomization chosen [25, 30 – 34].

Only two of the studies were blinded [25, 29]. None of

them were concealment allocation and were not described

as criteria for inclusion and exclusion and the sample size

that provides a high risk of bias. None of the studies described the dose – response data of

each effective animal model or optimal time window for re-

search that provides an unclear risk of bias.

All studies [6, 7, 25 – 34] report and use minimal mor-

bidity and describe the animal test that provides a low risk

of bias. All studies [6, 7, 25, 26, 28 – 34] explain the sta-

tistical method used least such as the study by Kim et al.

[27] that provides a low risk of bias. In some studies, it is

unclear if there is any conflict of interest [6, 7, 25, 27,

30 – 32] that provides an unclear risk of bias and other

studies [26, 28, 29, 33] may have a possible conflict of

interest that provides a high risk of bias. Only in the studyof Gomes et al. [34] did there appear to be no conflict of

interest that provides a low risk of bias.

In some studies [6, 27, 30, 31], there is unclear com-

pliance with animal welfare requirements that provides an

unclear risk of bias and, in studies of Lopes et al. [26, 28]

and Primo et al. [32], there is a high risk. The rest of the

studies have a low risk of bias [7, 25, 29, 33, 34].

Discussion

In recent years, there has been a great development in

research on low-level laser therapies for the dentistry field

and a specialized use in areas such as implantology

[35 – 37].

In animal studies, the results in the group irradiated

with low-power laser on titanium implants reported ben-

eficial results from the microscopic point of view such as

increased bone – implant contact [25, 29 – 31, 34]; better

connection between bone – implant [6]; greater percentage

of calcium and phosphorus [25]; greater percentage of

calcium hydroxyapatite [26, 28]; increases in the produc-

tion of OPG, RANKL, and RANK [34]; and no effect on

bone resorption [7].

Khadra et al. suggest that in the irradiated group, faster

bone maturation [25] helps improve bone healing [26] and

increases the cellular activity of tissues [34], with increased

activity of ATP ( p< 0.05) and a greater increase and viability

of the osteocytes compared to the control group (non-

irradiated) [7].

In the recommendations by Krauth et al. [21], there is

no classification based on the 13 categories or proposed

domains. However, the evaluation of each of the items

generally reveals that there may be a high risk of bias in

animal studies.

Human studies reported no statistically significant results

from the macroscopic point of view [23, 24]. This was used in

both GaAlAs lasers, but under different bone densities: great

[23] and poor [24] as well as different types of implant: no

self-tapping [23] and self-tapping [24].

These very poor results in humans can be caused bythe implant surface used and applied with the laser dose.

Primo et al. [32] revealed that the implant surface may

influence the results in addition to the strength of bone –

implant interface rough surfaces compared to smooth sur-

faces or treated with low-power laser. Studies of Massotti

et al. [33] and Gomes et al. [34] show that the dose of

low-power laser influences the integration of the implant

with the bone, agreeing that the dose of 20 J/cm2 is the

most effective. Some authors [23, 25] agree that there is

no standard protocol, although laser irradiation has been

defined to the field of implantology.

In the studies included in this systematic review, a widevariation in the election of the energy density, the number

of applications, and the wavelengths of low-power laser

used in implant therapy is observed. The assessment of

methodological quality in animal and human studies sug-

gests that it is necessary to determine a specific protocol

using a low-power laser that would allow for more con-

clusive studies with meta-analysis.

Conclusion

As a general conclusion, it should be observed that despite

the fact that LLLT has proved to provide multiple benefits

regarding tissue regeneration, there are not enough clinical

studies which analyze the effects of this treatment on im-

plant osseointegration. It can be drawn from this update

that, according to experimental research results, LLLT

might be a useful help to the osseointegration process,

although in the current state of knowledge, there is a lack

of human clinical studies.

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