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archives of oral biology 60 (2015) 347356

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Influence of orthodontic forces on human dental

pulp: A systematic review

Fawad Javed a, AbdulAziz A. Al-Kheraif b, Enisa B. Romanos a,

Georgios E. Romanos c,*
Division of General Dentistry, Eastman Institute for Oral Health, University of Rochester, Rochester, NY, USA.
Research Chair for Dental Biomaterials, Dental Health Department, College of Applied Medical Sciences, King Saud
University, Riyadh 11541, Saudi Arabia
Department of Periodontology, School of Dental Medicine, Stony Brook University, Stony Brook, NY, USA

article info abstract

Article history: Aim: The aim of the present study was to systematically review the influence of orthodontic
Accepted 17 November 2014 force on human dental pulp.
Methods and results: The addressed focused question was Do orthodontic forces affect the
Keywords: human dental pulp? which was based on the Preferred Reporting Items for Systematic
Dental pulp Reviews and Meta-Analyses (PRISMA) guidelines, a specific question was constructed
Growth factors according to the PICO (Participants, Interventions, Control, Outcomes) principle. Databases
Orthodontic force were explored from 1952 up to and including August 2014 using different combinations of
Pulpal blood flow the following keywords: orthodontic force; dental pulp; reaction and tooth move-
ment. Literature reviews, letters to the editor, commentaries and case-reports were
excluded. Thirty studies were included. Six studies assessed the effect of orthodontic forces
on pulpal blood flow and 20 studies investigated the pulpal cellular responses to orthodontic
forces. In 4 studies, pulpal responses to orthodontic forces were compared between
previously traumatized- and non-traumatized teeth.
Conclusions: There is insufficient scientific validation regarding the association between
orthodontic forces and human dental pulp. However, a history of dental trauma maybe
considered a risk factor for loss of pulp vitality during orthodontic treatment.
# 2014 Elsevier Ltd. All rights reserved.


1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 348
2. Materials and methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 348
2.1. Focused question. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 348
2.2. Search protocol . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 348

* Corresponding author. Tel.: +1 631 632 8755.

E-mail address: Georgios.Romanos@stonybrookmedicine.edu (G.E. Romanos).
00039969/# 2014 Elsevier Ltd. All rights reserved.
348 archives of oral biology 60 (2015) 347356

2.3. Quality assessment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 349

2.4. Level of evidence . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 349
3. Results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 350
3.1. Effect of orthodontic forces on pulpal blood flow. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 350
3.2. Influence of orthodontic forces on the cellular responses of the human dental pulp . . . . . . . . . . . . . . . . . . . . 350
3.3. Influence of orthodontic forces on the pulpal response in traumatized teeth. . . . . . . . . . . . . . . . . . . . . . . . . . 350
3.4. Quality assessment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 350
4. Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 350
5. Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 355
Acknowledgements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 355
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 355

1. Introduction 2. Materials and methods

Application of orthodontic forces to teeth for specific time 2.1. Focused question
periods has been reported to induce molecular changes in the
cells of the periodontal ligament, alveolar bone and the pulp Based on the Preferred Reporting Items for Systematic Reviews
dentine complex.17 Histologic studies have reported depres- and Meta-Analyses (PRISMA) guidelines, a specific question
sion of pulp tissue respiration, vacuolization, circulatory was constructed according to the PICO (Participants, Inter-
disturbances, haemorrhage, fibro-hyalinosis and even necro- ventions, Control, Outcomes) principle.22 The addressed
sis as the major pulpal changes that may be encountered focused question was Do orthodontic forces affect human
following the application of orthodontic forces to teeth.1,2,4 dental pulp?
Hamersky et al.7 suggested that excessive and prolonged (P) Participants: It was essential for participants to have
orthodontic forces when applied to teeth may result in loss of undergone orthodontic treatment.
pulp vitality. (I) Types of interventions: The interventions of interest
Laser Doppler flowmetry (LDF) by McDonald and Pitt Ford8 were orthodontic forces (such as intrusion, extrusion, tipping,
have reported a temporary decrease in pulpal blood flow (PBF). arch expansion and retraction).
The decrease in PBF has been associated with a drop in the (C) Control intervention: Teeth, which were either not
oxygen tension thereby increasing the possibility of cellular subjected to orthodontic forces or pulp tissues which treated
injury and apoptosis as determined by alterations in the with antibodies other than those used in the test-groups, were
expression of pulpal markers such as Aspartate Aminotrans- considered as controls.
ferase (AST) and alkaline phosphatase (ALP).911 However, (O) Outcome measures: Human pulpal response to ortho-
results by Barwick and Ramsay12 and Brodin et al.13 reported dontic forces.
no significant effect of a orthodontic forces (intrusive and/or
extrusive) on PBF. Studies5,1416 have also reported that 2.2. Search protocol
application of orthodontic forces on teeth for certain periods
of time increase the expression of various growth factors (GFs), In order to identify studies relevant to the PICO question, the
such as epidermal growth factor (EGF), platelet derived growth MEDLINE (OVID) database, the EMBASE database, the
factor (PDGF), vascular endothelial growth factor (VEGF), Cochrane Central Register of Controlled Trials (CENTRAL),
fibroblast growth factor-2 (FGF-2) and transforming growth Scopus, Web of Knowledge, The Cumulative Index to Nursing
factor beta (TGF-b) in pulpal tissues, which in turn contribute and Allied Health Literature and Google-Scholar databases
to angiogenesis. were electronically searched for available data. Databases
High levels of inflammatory mediators, such as interleu- were searched from 1954 up to and including August 2014
kin (IL)-6, IL-1b tumour necrosis factor alpha and receptor using different combinations of the following key words:
activator of nuclear factor kappa B have been identified in orthodontic force; human dental pulp; reaction and
pulpal tissues of teeth exposed to orthodontic forces.17,18 tooth movement. Titles and abstracts of studies identified
Levels of inflammatory mediators in the gingival crevicular using the above-described protocol were screened by two
fluid have also been reported to be significantly elevated authors (FJ AAK and GER) and checked for agreement. Full-
during orthodontic therapy.19,20 Therefore, from a clinical texts of studies judged by title and abstract to be relevant were
perspective, it is hypothesized that long-term application of read by authors (FJ AAK and GER) and independently evaluated
orthodontic forces jeopardizes pulp vitality. Furthermore, in accordance with the following eligibility criteria: clinical
pulpal necrosis (PN) has also been reported after the studies, application of orthodontic force on teeth and
induction of orthodontic forces such as intrusion, extrusion assessment of pulp tissues. Kappa scores (Cohens kappa
and retraction.8,21 It is tempting to speculate that the coefficient) were employed to determine the level of agree-
magnitude of pulpal inflammation or injury is directly ment between the two reviewers.23,24 Letters to the Editor,
proportional to the degree of orthodontic force applied on historic reviews, commentaries, experimental (animal) stud-
the teeth. ies and case-reports were excluded. Hand-searching of
The aim of the present study was to systematically review potentially relevant original and review articles was also
the influence of orthodontic force on human dental pulp. performed. This was done to identify any studies that could
archives of oral biology 60 (2015) 347356 349

Records identified Records Records Records Records identified Records identified

through identified identified identified through Cochrane through Google-
MEDLINE through PubMed through through Web of Central Register Scholar
(n=44) (n=78) (n=0) (n=98) (n=2) (n=79)

Total number of records

(n = 301)

Records screened Records excluded

(n = 105 ) (n = 60 )

Full-text articles assessed Full-text articles excluded,

for eligibility with reasons
(n = 45 ) (n = 15 )

Studies included in
qualitative synthesis
(n = 30 )

Fig. 1 Literature search strategy according to the PRISMA guidelines (www.prisma-statement.org).

have remained unidentified in the previous step and checked end points; and diagnostic reliability tests and reproducibil-
for disagreement via discussion among the authors. Articles ity tests described (all criteria should be met; otherwise,
available online in electronic form ahead of print were grade C).
considered eligible for inclusion. Fig. 1 summarizes the  Grade C (Low)One or more of the following settings are
literature search strategy according to the PRISMA guidelines. encountered: poorly defined patient material, unclear
The pattern of the present systematic review was customized diagnosis and end points and large attrition of the
to mainly summarize the relevant data. samples.

2.3. Quality assessment 2.4. Level of evidence

Three authors (FJ, AAK and GER) independently assessed the For each study included in the present review, level of
methodological quality of the included studies according to a evidence was judged in accordance with the following scale26:
grading system developed by the Swedish Council on
Technology Assessment in Health Care.25 The following
criteria were used for assessing the methodological quality  Strong Scientific Support (Evidence Grade 1)Conclusion is
of the studies included in the present review: based on at least 2 studies with level A-evidence. Studies
with opposite conclusions may lower the evidence grade.
 Moderately Strong Support (Evidence Grade 2)Conclusion
 Grade A (High)A randomized controlled trial or prospec- is based on 1 study with strong evidence (A) and at least 2
tive study, composed of a well-defined control group; with moderately strong evidence (B). Studies with opposite
defined diagnosis and end points; diagnostic reliability tests conclusions may lower the evidence grade.
and reproducibility tests described; and blinded outcome  Limited Scientific Support (Evidence Grade 3)Conclusion is
measurements (all criteria should be met). based on at least 2 studies with moderately strong evidence
 Grade B (Moderate)A cohort study or retrospective study, (B). If studies contradicting the conclusion exist, the
composed of a defined control group; defined diagnosis and scientific basis is judged as contradictory or insufficient.
350 archives of oral biology 60 (2015) 347356

 Inconclusive Scientific Support (Evidence Grade 4)If of orthodontic force in the study by Parris et al.32 and Subay
studies fulfilling the evidence criteria are lacking, the et al.29 reported no evidence of inflammatory reactions in the
scientific basis for conclusion is considered insufficient. pulps of orthodontically-moved teeth (Table 2).

3. Results 3.3. Influence of orthodontic forces on the pulpal response

in traumatized teeth
3.1. Effect of orthodontic forces on pulpal blood flow
Four studies3841 investigated the pulpal reaction of orthodon-
Six studies addressed the effect of orthodontic tic forces on traumatized teeth. Two studies38,40 reported the
forces on PBF (Table 1). The numbers of study participants magnitude of orthodontic force applied on traumatized teeth,
ranged between 6 and 21 patients. In 5 studies,4,8,12,13,28 which were 0.2 N and 0.15 N. In these studies,3841 duration of
orthodontic forces were applied to achieve extrusion, intru- orthodontic treatment in previously traumatized teeth ranged
sion and retraction of premolar teeth; whereas in the study by between 22.4 and 54 months. All studies3841 reported PN to be
Babacan et al.,27 rapid maxillary expansion (RME) was more frequent when orthodontic treatment was performed in
performed. Five studies4,8,12,13,28 reported the orthodontic previously traumatized teeth as compared to non-trauma-
force applied to teeth which ranged between 0.5 Newton (N) tized teeth (Table 3).
and 44 N. In one study27 the amount of orthodontic force
applied to perform RME was not reported. In these stud- 3.4. Quality assessment
ies,4,8,12,13,27,28 the duration for which orthodontic forces were
applied ranged between 20 s and 152 days. Three studies4,13,28 Most of the studies were graded as moderate to low mainly
reported that intrusive orthodontic forces temporarily reduce because of their methodological quality (Tables 13). Low
PBF; and in the study by Barwick and Ramsay12 PBF remained grading was mainly based on no randomized assignment to
unaltered during all orthodontic treatment sessions. In the experimental and control treatment groups and no descrip-
study by Babacan et al.,27 PBF increased in the first week of tion of reliability tests.
RME and decreased significantly by the third week of RME.

3.2. Influence of orthodontic forces on the cellular 4. Discussion

responses of the human dental pulp
Since grading evidence is a complicated issue, we avoided
Twenty studies1,5,7,9,11,1416,21,2937 reported the influence of using a scale that allocates points to individual quality items
orthodontic forces on human pulpal cellular responses because this approach has proved to be inadequate.42 To our
(Table 2). In 18 studies,13,5,7,9,11,1416,21,2932,34,36,37 orthodontic knowledge from indexed literature, a gold standard quality
forces were applied on premolars and in 2 studies33,35 teeth assessment tool is still missing.43,44 Lack of randomized
exposed to orthodontic forces were not reported. The controlled trials and a disharmony in the study protocols
magnitude of orthodontic force ranged between 0.3 N and are limitations of the studies included in this review. These
6 N for durations ranging between 21 min and 84 days. factors may be held responsible for the moderate to low
Intrusion, extrusion and tipping movements were performed grading of most studies included in this review.
in 8,1,11,30,31,3437 83,5,7,14,16,21,29,33 and 39,15,32 studies, respec- In a systematic review published in the year 2012, von Bohl
tively. In one study,2 both intrusion and extrusion forces were et al.,45 reported that there is no conclusive scientific evidence
applied on premolars. Results by Lazzaretti et al.37 showed for a relation between force level and dental pulp tissue
that intrusive orthodontic forces caused vascular changes in reaction in humans. Authors of this systematic review
the pulpal tissue and also increased the presence of fibrosis emphasized that there is a scarcity of long-term results
and the number of pulp calcifications. Four studies1,2,21,36 regarding pulpal injury occurring as a result of orthodontic
reported orthodontic forces to cause vacuolization and treatment.45 Since there is a debate among clinicians regard-
disruption of osteoblasts in pulpal tissues but without ing the optimal orthodontic forces that teeth can endure
necrosis. Results by Caviedes-Bucheli et al.3 reported ortho- without experiencing massive pulpal inflammation and/or
dontic forces of 0.56 N and 2.24 N to increase the pulpal necrosis, we were tempted to re-search indexed literature to
expression of calcitonin gene-related peptide (CGRP) as identify additional studies (published after the year 2012) that
compared to the control group. Three studies5,14,16 reported assessed the association between orthodontic force and its
orthodontic forces to increase the expression of GFs in pulpal effects on human dental pulp tissues. Moreover, in the
tissues. Perinetti et al.9 and Veberiene et al.11 reported systematic review by von Bohl et al.45 the effect of orthodontic
orthodontic forces to increase pulpal AST activity. In one forces on human dental pulp were assessed in non-trauma-
study,34 pulpal AST levels were comparable with and without tized teeth only; however, in the present systematic review,
mechanical load application. Kucukkeles and Okar31 showed we reviewed pertinent literature regarding the influence of
vascular degeneration in the pulps of orthodontically treated orthodontic forces on human dental pulp tissues of non-
teeth; Derringer et al.15 reported angiogenesis to be signifi- traumatized and traumatized teeth.
cantly higher in orthodontically-treated teeth and control In the present study, a systematic review of pertinent
teeth. In 4 studies,30,33,35,36 orthodontic forces were reported to literature was performed in an attempt to assess the effect of
cause minor disturbances in pulpal circulation. Concentration orthodontic forces on dental pulp tissues. It was hypothesized
of substance P was negatively correlated with the magnitude that long-term application of orthodontic forces jeopardizes
Table 1 Studies on the effect of orthodontic forces on pulpal blood flow.
Authors et al. Design Study Type of Control Force Duration Pulpal blood flow Results Quality grade
subjects treatment group applied (N) of force measured by
Sano et al.4,*

archives of oral biology 60 (2015) 347356

Prospective 13 Intrusion 13 vital teeth 0.5, 1, 2 14 days LDF Intrusive forces temporarily B
without reduced PBF. PBF changes
orthodontic force returned to normal at the
application end of force application
McDonald and Prospective 10 Canine 10 vital teeth 0.5 Up to 4 days LDF PBF increased up to 48 h of B
Pitt Ford8,* retraction without load application but returned
orthodontic force to preload values within 72 h
Barwick and Prospective 8 Intrusion None 0.75, 1.25, 112 days LDF Baseline PBF remained A
Ramsay12,y 5, 44 unchanged during all
treatment sessions
Brodin et al.13,y Prospective 6 Intrusion and None 0.5 152 days LDF Extrusion had no significant C
extrusion effect on PBF. Intrusion
reduced the pulpal blood flow
by 20% during the first minute
Babacan et al.27,y Prospective 21 RME None NR Up to LDF PBF increased in the 1st week B
84 days and decreased significantly by
the 3rd week of RME
Ikawa et al.28,* Prospective 17 Intrusion None 0.5, 1, 5 20 s LDF Brief intrusive forces B
temporarily reduced PBF
LDF, laser Doppler flowmetry; NR, not reported; OT, orthodontic treatment; PBF, pulpal blood flow; RME, rapid maxillary expansion.
High risk of bias.
Low risk of bias.

Table 2 Studies on the influence of orthodontic forces on the cellular responses of the dental pulp.
Authors et al. Design Subjects Number Type of Force Control Duration Pulpal response Conclusion Quality
of teeth movement applied group of force grade
Lazzaretti Prospective 17 34 Intrusion 0.58 No orthodontic 21 days There was a significant Intrusive orthodontic forces B
et al.37,y force applied increase in the number of caused vascular changes in
pulpal nodules in the the pulpal tissue and also
elements with no difference in increased the presence of
the number of blood vessels fibrosis and the number of
between the groups pulp calcifications
Han et al.1,y Prospective 27 54 Intrusion 0.5, 3 No orthodontic Up to In both force groups, Intrusive orthodontic forces C
force applied 84 days odontoblasts disruption, do not jeopardize pulp
vacuolization and moderate vitality
vascular congestion

archives of oral biology 60 (2015) 347356

occurred but without PN
Ramazanza-deh Prospective 26 52 Intrusion and 0.25, 0.74 No orthodontic Up to In both force groups, Histologic pulpal changes C
et al.2,* extrusion force applied 21 days odontoblasts disruption, between baseline and 21 days
vacuolization and moderate showed no statistically
vascular congestion significant difference
occurred but without PN
Caviedes-Bucheli Prospective NR 30 Extrusion 0.56, 2.24 No orthodontic 1 day In both force groups, pulpal Orthodontic forces increase C
et al.3,* force applied CGRP expression was CGRP expression in human
increased compared to the dental pulp
control group
Derringer and Prospective 20 80 Extrusion 0.51 Use of antibodies 14 days VEGF, FGF-2, PDGF and Growth factors are C
Linden5,* (In vitro) other than those TGF-b are released expressed in the pulp of
for VEGF, FGF2 following orthodontic force teeth exposed to
and TGFbeta application mechanical load
Hamersky et al.7,* Prospective 17 68 Extrusion At least No orthodontic 3 days Short-term orthodontic forces Orthodontic forces cause C
0.6 N force applied caused pulpal tissue hypoxia biochemical and biologic
pulpal tissue alterations
Perinetti et al.9,* Prospective 17 17 Tipping 0.30.9 No orthodontic 7 days Mean AST activity and EPT Application of mechanical B
force applied values were significantly load to teeth can cause
higher in teeth exposed to metabolic changes in the
mechanical load compared to pulp
Veberiene Prospective 21 42 Intrusion 0.61 No orthodontic 7 days Mean AST activity and EPT Application of mechanical A
et al.11,* force applied values were significantly load to teeth can cause
higher in teeth exposed to metabolic changes in the
mechanical load compared pulp
to controls
Derringer and Prospective 10 10 Extrusion 0.51 Co-cultures 14 days Orthodontic forces EGF released following B
Linden14,y (In vitro) without anti-h stimulate the release of EGF orthodontic force
EGF in pulp tissues application plays a role in
pulpal angiogenic response
Derringer et al.15,* Prospective NR 30 Tipping 0.51 No orthodontic 5 days There were significantly Growth factors are expressed B
force applied greater numbers of micro- in the pulp of teeth exposed
vessels in orthodontically to mechanical load
treated teeth than control teeth
Derringer and Prospective 18 18 Extrusion 0.51 No orthodontic 14 days VEGF, FGF-2, PDGF and TGF-b Growth factors play a role in B
Linden16,y force applied are released following pulpal angiogenesis
orthodontic force application
Mostafa et al.21,y Prospective 18 36 Extrusion 0.5 No orthodontic Up to 28 Dilated and constricted blood Orthodontic forces can cause B
force applied days vessels, odontoblastic temporary inflammation and
degeneration, vacuolization fibrosis in pulpal tissues
and oedema of the pulp tissues,
and fibrotic changes occurred
in pulpal tissues
Subay et al.29,y Prospective 15 40 Extrusion 0.75 No control group 10 days, There was no evidence of in- Extrusive forces do not cause C
(All teeth were ex- 40 days flammatory reactions and/or significant pathological
truded) reparative dentine formation changes in pulp tissues

archives of oral biology 60 (2015) 347356

in all teeth
Raiden et al.30,y Prospective 20 40 Intrusion 1.5 No orthodontic 1520 Histologic results showed Intrusive forces can cause C
force applied days alterations in predentine, congestion, haemorrhage and
calcium deposition, fibrohyalinosis in the pulp
fibrohyalinosis, congestion, tissues
inflammation and
Kucukkeles Prospective 2 4 Intrusion 1.5 No orthodontic 90 days Vascular degeneration Intrusive forces jeopardize C
and Okar31,y force applied occurred in the pulps of pulp vitality by causing
orthodontically-treated teeth. vascular degeneration.
Parris et al.32,* Prospective 20 80 Tipping 1.2, 1.4, 1.5, No orthodontic 2178 min Concentrations of ir-ME and Orthodontic forces and B
1.8, 2, 2.1, force applied ir-SP each correlated negatively pulpal ir-ME and ir-SP
2.15, 2.3, 2.45 with the magnitude of the concentrations are
and 6 orthodontic force interlinked

Stenvik33,y Prospective NR NR Extrusion 12 No orthodontic 714 days Minor reactions related to the Orthodontic forces cause C
force applied pulpal circulatory system can biochemical and biologic
occur pulpal tissue alterations
Veberiene Prospective 13 26 Intrusion 0.65 No orthodontic 14 days Mean pulpal AST levels and Orthodontic forces do not A
et al.34,y force applied EPT values similar with and influence pulpal AST activity
without mechanical load and EPT values
Stenvik and Prospective NR 25 Intrusion 0.52.5 No orthodontic 528 days Minor reactions related to the Orthodontic forces cause C
Mjor35,y force applied pulpal circulatory system can biochemical and biologic
occur pulpal tissue alterations
Stenvik a n d Prospective NR NR Intrusion 0.352.5 No orthodontic 435 days Vacuolization of the pulp tissue Orthodontic forces cause C
Mjor36,y force applied and circulatory disturbances biochemical and biologic
occurred pulpal tissue alterations
ALP, alkaline phosphatase; AST, aspartate aminotransferase; Control, mechanical load not applied; CGRP, calcitonin gene-related peptide; EGF, epidermal growth factor; EPT, electric pulp testing; ir-
ME, immunoreactive methionine enkephalin; ir-SP, immunoreactive substance P; NR, not reported; PM, premolars.
High risk of bias.
Low risk of bias.

354 archives of oral biology 60 (2015) 347356

pulp vitality; however, due to a variation in the magnitude and

duration of orthodontic forces exerted on teeth in the studies
included, it is exigent to scientifically validate the aforemen-

tioned hypothesis. Amongst the studies4,8,12,13,27,28 which

Loss of pulp vitality was more

Group-1 than groups 2 and 3

assessed the influence of orthodontic forces of PBF, magnitude
and duration of orthodontic force applied varied considerably

PN was more frequent in

PN was more frequent in

PN was more frequent in

frequent among teeth in

Group-1 than Group-2

Group-1 than Group-2

Group-1 than Group-2

(0.5 N44 N and 20 s152 days, respectively). It is allured that a

low orthodontic force (for instance 0.5 N) exerted on teeth for a

few minutes causes minor or no change in PBF than the same
force being applied for longer durations. However, scientific
or Group-3

or Group-3
evidence in this regard is still missing. Likewise, it may also be
argued that long-term application of intense orthodontic
forces to teeth influences PBF to a significantly greater extent
than when the same forces are applied for a short duration.
OT (months)
Duration of




39.6 Therefore, it is difficult to contemplate a direct association



between PBF and magnitude of orthodontic force. It has also

been reported that the effects of orthodontic forces on PBF are
associated with various factors including patientsage, size of
apical foramen, dentinogenic activity and not merely on the
magnitude and duration of the force applied.7,12 None of the
Group-3 (Control group)

studies4,8,12,13,27,28 that fulfilled the eligibility criteria assessed

dental trauma and OT
193 traumatized teeth

193 traumatized teeth

193 traumatized teeth

the influence of size of apical foramen on PBF in the study

26 patients* without

groups. It is however pertinent to mention that in these

studies4,8,12,13,27,28 age of the study participants was also
Table 3 Studies on the influence of orthodontic forces on the pulpal response in traumatized teeth.

without OT

without OT

without OT

markedly incoherent. For example, in the study by Sano et al.,4

individuals with age ranging between 27 and 31 years were
included; whereas Babacan et al.,27 assessed the effect of
orthodontic forces on PBF among 1015 year old patients.
Further clinical trials with standardized parameters (particu-
OT in 400 non-traumatized

800 teeth non-traumatized

Study groups

larly magnitude and duration of force application) are needed

OT in 29 patients* with
non-traumatized teeth

to clarify the effect of orthodontic forces on PBF.


CGRP is a potent vaso-dilatory peptide that is found in

approximately 50% of the neurons of the trigeminal system.46,47
Substance P (SP) is mediator of neurogenic inflammation and
during OT

causes vasodilatation by direct action over endothelial cells and


indirect mast cell stimulation for histamine release, a dual

effect shared with CGRP.48 These molecules are capable of

provoking a tolerable discomfort among patients following the
59 teeth traumatized

OT in 269 previously
OT in 77 previously

OT in 54 previously

activation of orthodontic intrusive forces.49 In the study by

traumatized teeth

traumatized teeth

traumatized teeth

Caviedes-Bucheli et al.,3 orthodontic extrusion was associated


with an increased expression of CGRP in the pulp. However, in

during OT

this study,3 CGRP levels were measured after 24 h of force

application. Likewise, Parris et al.,32 measured pulpal SP levels
after 0.31.3 h after force application. To assess the significance
of the results reported by Caviedes-Bucheli et al.,3 and Parris
applied (N)

et al.,32 further studies with long-term application of orthodon-


tic force are warranted.

Angiogenesis is defined as the process of development of


new blood vessels from preexisting microvasculature. GFs

may act either directly or indirectly to regulate the endothelial




cell function and expression of other GFs by different cell


types.50 Studies5,1416 have used neutralizing antibodies (anti-

h VEGF, FGF2, PDGF, TGF-b and EGF) to investigate the
presence of a combination of GFs in the human dental pulp
during orthodontic force application. The neutralizing anti-
Authors et al.

bodies significantly reduced the number of microvessels in the

Bauss et al.38

Bauss et al.39

Bauss et al.40

Brin et al.41

evaluated in vitro cultures thereby confirming the presence of

GFs in the pulp during orthodontic movement. This is an
explanation for the study by Derringer et al.,15 in which the
authors showed the presence of significantly greater numbers
archives of oral biology 60 (2015) 347356 355

of micro-vessels in orthodontically treated teeth than control

teeth. Furthermore, in an experimental study on mice, Kaku Competing interest
et al.,51 investigated the effect of recombinant human VEGF
(rhVEGF) on the differentiation of osteoclasts during experi- The authors declare that they have no conflict of interest.
mental tooth movement. The results suggested that local
administration of rhVEGF enhances the number of osteoclasts
and may increase the rate of orthodontic tooth movement. Ethical approval
It is known that pulpal fibroblasts and odontoblasts
synthesize and release ALP.52,53 Therefore, it is hypothesized Not required.
that application of orthodontic force on these cells reduces their
ALP expression. AST is an essential mediator of inflammatory
processes and is expressed in high concentrations in pulpal Acknowledgement
inflammatory conditions.54 Raiden et al.,30 Perinetti et al.,9
Veberiene et al.,11 reported raised pulpal AST levels following The authors extend their appreciation to the Research Center,
the application of intrusive orthodontic forces, which reflect a College of Applied Medical Sciences and Deanship of Scientific
state of inflammation in the pulp. However, due to a limited Research at King Saud University for funding this research. The
number of studies that have assessed pulpal AST and ALP levels authors also thank the Visiting Professor Program at King Saud
during orthodontic force application, the significance of these University, Saudi Arabia for supporting this research project.
enzymes affecting pulpal tissues remains veiled.
A critical factor that could have biased the outcome of the
studies included in the present review is their design and
methodology. For example, in the studies4,8,12,13,27,28 which
assessed the influence of orthodontic forces on human dental
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pulp, magnitude of force applied to teeth varied dramatically changes in human dental pulp after the application of
among as well as between the studies (0.544 N). Similarly, moderate and severe intrusive orthodontic forces. Am J
among studies that assessed the cellular response of dental Orthod Dentofacial Orthop 2013;144(4):51822.
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of forces used in these studies also varied (0.36 N). It is Hassanzadeh N, Jahanbin A, Shakeri MT. Histological
changes in human dental pulp following application of
therefore tempting to speculate that an intense orthodontic
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