UNIVERSIDADE ESTADUAL PAULISTA
“JÚLIO DE MESQUITA FILHO”
Instituto de Ciência e Tecnologia
Campus de São José dos Campos
SYSTEMATIC REVIEW DOI: https://doi.org/10.4322/bds.2024.e4374
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Braz Dent Sci 2024 Oct/Dec;27 (4): e4374
This is an Open Access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in
any medium, provided the original work is properly cited.
Effect of bisphosphonate use on orthodontic tooth movement:
a systematic review
Efeito do uso de bifosfonatos na movimentação dentária ortodôntica: uma revisão sistemática
Gurgiane Rodrigues Gurgel LESSA1 , Mariana Cabral MORENO1 , Eloísa Cesário FERNANDES1 ,
Halissa Simplício Gomes PEREIRA1 , Ruthinéia Diógenes Alves Uchôa LINS1
1 - Federal University of Rio Grande do Norte, Department of Dentistry, Natal, RN, Brazil.
How to cite: Lessa GRG, Moreno MC, Fernandes EC, Pereira HSG, Lins RDAU. Effect of bisphosphonate use on orthodontic tooth
movement: a systematic review. Braz Dent Sci. 2024;27(4):e4374. https://doi.org/10.4322/bds.2024.e4374
ABSTRACT
Background: As bisphosphonates have an action mode which interferes in the osteo-resorptive process, their use
during dental treatment may occasionally have side effects, such as: inhibition of tooth movement, delayed bone
healing, and osteonecrosis in the maxilla and mandible. Objective: The present study proposed a systematic review
of the literature on the effect of systemic use of bisphosphonates on orthodontic tooth movement. Methods: This
systematic review was developed based on PRISMA guidelines and the inclusion criteria were: written in English,
approach the relationship between the use of bisphosphonates and orthodontic movement as the research objective
and experimental study in rats. We excluded studies which did not evaluate orthodontic movement and those in
which bisphosphonates were not the main analytical substance. The question raised was: “Does the systemic use
of bisphosphonates interfere in orthodontic movement?” Classication of the risk of bias that studies was veried
using the SYRCLE. Results: We initially identied 51 articles in the electronic search. This number was then reduced
to 13 publications after the analysis of titles and abstracts. And 8 articles included for nal analysis. Conclusion:
Most studies of this systematic review point to the fact that the systemic use of bisphosphonates during orthodontic
treatment seems to reduce the extent and speed of tooth movement, thus extending the treatment duration.
KEYWORDS
Bisphosphonates; Bone and bones; Rats; Systematic review; Tooth movement techniques.
RESUMO
Contexto: Como os bifosfonatos possuem um modo de ação que interfere no processo osteorreabsortivo, seu uso
durante o tratamento odontológico pode ocasionalmente ter efeitos colaterais, tais como: inibição da movimentação
dentária, retardo na consolidação óssea e osteonecrose na maxila e mandíbula. Objetivo: O presente estudo propôs
uma revisão sistemática da literatura sobre o efeito do uso sistêmico de bifosfonatos na movimentação dentária
ortodôntica. Métodos: Esta revisão sistemática foi desenvolvida com base nas diretrizes e recomendações PRISMA
e incluiu: estudos escritos em inglês, que abordavam a relação entre o uso de bifosfonatos e a movimentação
ortodôntica como objetivo da pesquisa e do tipo experimental em ratos. Foram excluídos estudos que não avaliaram
a movimentação ortodôntica e aqueles em que o bifosfonato não era a principal substância analisada. A questão
levantada foi: “O uso sistêmico de bifosfonatos interfere na movimentação ortodôntica?” A classicação do risco
de viés dos estudos foi vericada usando o SYRCLE. Resultados: Identicamos inicialmente 51 artigos na busca
eletrônica. Esse número foi então reduzido para 13 publicações após a análise dos títulos e resumos. E 8 artigos
incluídos para análise nal. Conclusão: A maioria dos estudos desta revisão sistemática aponta para o fato de
que o uso sistêmico de bifosfonatos durante o tratamento ortodôntico parece reduzir a extensão e a velocidade da
movimentação dentária, prolongando assim a duração do tratamento.
PALAVRAS-CHAVE
Bisfosfonatos; Osso; Ratos; Revisão sistemática; Técnicas de movimentação dentária.
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Lessa GRG et al.
Effect of bisphosphonate use on orthodontic tooth mov ement: a systematic re view
Lessa GRG et al. Effect of bisphosphonate use on orthodontic tooth movement:
a systematic review
INTRODUCTION
Bone remodeling is the basis of tooth
movement, in which osteoclasts act to promote
reabsorption of mature bone, while osteoblasts
promote bone neoformation. This process is
regulated by several local and systemic factors.
Regarding systemic factors capable of interfering
with the bone remodeling process, it is possible
to include the age, nutrition and consumption of
different types of drugs such as bisphosphonates,
especially in view of the high impact it causes on
bone and bone tissue and the increased frequency
of use in recent years [1,2].
Bisphosphonates currently represent the
therapy of choice for treating osteoporosis and
are indicated for preventing and treating skeletal
complications in cancer patients. Are a class of
drugs highly effective in the treatment of various
bone diseases, such as osteoporosis, Paget disease
and bone metastasis [3,4]. Used for the treatment
of several osseous disorders. The main subtypes
of are alendronate, ibandronate, risedronate,
pamidronate, clodronate, and zoledronic
acid [5]. Studies have shown that these drugs
may inuence the amount of tooth movement
and root resorption during orthodontic tooth
movement [6-8].
Among the BPs, alendronate (AL) is one of
the most commonly used drugs for the treatment
of bone disorders. In adition, bone preservation
and maintenance with the use of BPs, but it is
also known that long-term therapy may impair
bone strength, inadvertently altering bone
turnover and eventually causing osteonecrosis
of the jaw, micro damage and even pathologic
fractures [3]. Clodronate inhibits bone resorption
induced by orthodontic force [9,10]. Zoledronate
provide maximal anchorage in extraction space
closure [10]. Risedronate has a marked effect in
reducing the prevalence of periapical lesions and
based on the information compiled in rodents, it
can be assumed that the rate of orthodontic tooth
movement and tooth relapse movement may be
affected by the administration of risedronate [5].
In addition to joining hydroxyapatite crystals
in a mineralized bone matrix, making the
bone more resistant to the catabolic action
of osteoclasts, bisphosphonates inhibit the
function of these cells, inducing their apoptosis
and blocking reabsorption, and therefore bone
remodeling [11].
As bisphosphonates have an action
mode which interferes in the osteo-resorptive
process, their use during dental treatment may
occasionally have side effects, such as: inhibition
of tooth movement, delayed bone healing, and
osteonecrosis in the maxilla and mandible. Thus,
authors have suggested that these drugs may
alter bone physiology and potentially hinder
orthodontic treatment[11].
Case reports involving patients undergoing
bisphosphonate treatment have described a lower
rate of tooth movement in these individuals than
in those who did not use bisphosphonates along
with orthodontic treatment impairment, thus
justifying the need to investigate the extent of
changes in bone metabolism caused by consuming
this drug. In view of the above, the present study
proposed a systematic review of the literature on
the effect of systemic use of bisphosphonates on
orthodontic tooth movement [12,13].
MATERIAL AND METHODS
This systematic review was developed based
on PRISMA guidelines and recommendations
2020 [14] and included scientic articles published
until september 2023. The question raised was:
“Does the systemic use of bisphosphonates
interfere in orthodontic movement?”
Bibliographic research strategy and initial
selection of studies
An electronic search was conducted in
the following databases: PubMed, Medline,
Scopus, Cochrane Library and Clinical Trials.gov.
The following search strategies were employed
in these databases involving the descriptors:
Biphosphonates AND Orthodontic movement,
without restrictions with respect to the year of
publication. The inclusion criteria considered for
selecting the articles were: written in English,
approach the relationship between the use of
bisphosphonates and orthodontic movement as
the research objective and experimental study in
rats. We excluded studies which did not evaluate
orthodontic movement and those in which
bisphosphonates were not the main analytical
substance.
Due to the previously established inclusion
and exclusion criteria, two evaluators (G.R.GL
and M.C.M) blindly performed the rst selection
stage of the articles based on the individual
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Lessa GRG et al.
Effect of bisphosphonate use on orthodontic tooth mov ement: a systematic re view
Lessa GRG et al. Effect of bisphosphonate use on orthodontic tooth movement:
a systematic review
analysis of titles and abstracts of all works
found in the referenced databases. When there
was inconsistency among reviewers regarding
the inclusion of the scientific articles within
the systematic review, a meeting was held for
discussion and consensus. Then, the references
of each selected article were manually searched
in an attempt to obtain articles not found in the
rst stage of the bibliographic search.
Evaluation of the methodological quality of
the initially included studies
The initially selected studies were read in
full and those that met the inclusion criteria were
qualitatively analyzed through two tools based on
the study of Michelogiannakis et al. (2018) [15],
using the SYRCLE (Systematic Review Center
for Laboratory animal Experimentation) tool
adapted to verify aspects of the risk of bias of
the included studies, which plays an important
role in in vivo experiments (Table I), and the
ARRIVE tool (Animal Research Reporting in
Vivo Experiment), following the guidelines of
Kilkenny et al. (2010) [22] (Table II).
RESULTS
We initially identified 51 articles in the
electronic search. This number was then reduced
to 13 publications after the analysis of titles and
abstracts. The full texts were analyzed according
to the inclusion and exclusion criteria, resulting
in 8 articles qualied for the nal analysis, as
summarized in Figure 1.
The methodological characteristics of the in
vivo studies selected, such as: authorship, year of
publication, type of animal, gender, age, sample
size, study groups, dose, frequency and time
of drug use, applied force during orthodontic
movement, experimental unit, evaluated
parameters and analysis types performed are
described in Tables III, IV and V, while the main
results and conclusions of these studies are in
Table VI. The risk of bias classication (evaluated
through the SYRCLE tool) and the scores obtained
from the qualitative analysis of the experimental
criteria (performed according to the ARRIVE tool)
are described in Tables I and II, respectively.
DISCUSSION
Considering that orthodontic forces promote
physical and biological events critical to bone
renewal, including recruitment of inammatory
cells, formation of new vessels and tissue
remodeling, it is possible that the systemic
use of drugs inhibiting the osteo-reabsorption
process, such as bisphosphonates concomitantly
Figure 1 - Flowchart adapted from the PRISMA statement for systematic reviews [14].
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Lessa GRG et al.
Effect of bisphosphonate use on orthodontic tooth mov ement: a systematic re view
Lessa GRG et al. Effect of bisphosphonate use on orthodontic tooth movement:
a systematic review
Table I - Classification of the risk of bias verified using the SYRCLE tool, mean per item
Nº Risk of bias (SYRCLE) Franzonietal.
(2017) [16]
Seifietal.
(2017) [17]
Brunetetal.
(2016) [8]
Nakašetal.
(2017) [18]
Salazaretal.
(2015) [7]
Kaipatur etal.
(2013) [19]
Karrasetal.
(2009) [20]
Liuetal.
(2004) [21] Total (%)
1Was the allocation sequence generated and
applied properly? NI Yes Yes Yes Yes Yes Yes NI Low bias
(75%)
2
Were the groups similar at baseline or were
they adjusted for confounding factors in the
analysis?
NI Yes NI NI Yes Yes Yes Yes Low bias
(62.5%)
3 Was the allocation sequence properly blinded? NI Yes Yes Yes NI Yes Yes Yes Low bias
(75%)
4Were the animals randomly housed during the
experiment? NI Yes Yes Yes Yes Yes Yes Yes Low bias
(87.5%)
5
Were caregivers and/or researchers blinded to
the knowledge of intervention that each animal
received during the experiment?
NI NI NI NI NI NI NI NI
Inaccurate
data
(100%)
6Were the animals randomly selected for
outcome evaluation? NI NI NI NI NI NI NI NI
Inaccurate
data
(100%)
7 Was the outcome assessor blinded? NI Yes NI NI NI NI NI NI
Inaccurate
data
(87.5%)
8Were incomplete data results adequately
addressed? NI Yes NI NI NI NI NI NI
Inaccurate
data
(87.5%)
Legend: Low risk of bias: Proper randomization and concealment of allocation; answer “yes” to all questions about completeness of data and blindness results, and “no” in response to selective reporting and
other sources of bias; Clear risk of bias: one or more criteria were partially met; or (iii) High risk of bias: one or more criteria were not met.
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Effect of bisphosphonate use on orthodontic tooth mov ement: a systematic re view
Lessa GRG et al. Effect of bisphosphonate use on orthodontic tooth movement:
a systematic review
Table II - Scores of the experimental criteria analyzed qualitatively according to the
ARRIVE
tool
Nº ARRIVE Criteria Franzonietal.
(2017) [16]
Seifietal.
(2017) [17]
Brunetetal.
(2016) [8]
Nakaš etal.
(2017) [18]
Salazaretal.
(2015) [7]
Kaipatur etal.
(2013) [19]
Karrasetal.
(2009) [20]
Liuetal.
(2004) [21] Total (%)
1 Title 1 1 1 1 1 1 1 1 100%
2 Abstract 1 1 1 1 1 1 1 1 100%
Introduction
3 General information 1 1 1 1 1 1 1 1 100%
4 Primary and secondary objectives 1 1 1 1 1 1 1 1 100%
Metodology
5 Ethical statement 1 1 1 1 1 1 1 1 100%
6 Study design, allocation concealment, blinding and randomization 0 1 1 1 1 1 1 1 87.5%
7 Experimental procedure with precise details 1 1 1 1 1 1 1 1 100%
8Details of experimental animals, including species, sex, age, weight and
source 1 1 1 1 1 1 1 1 100%
9Housing and breeding conditions such as cage, light/dark cycle,
temperature, access to food and water 1 1 1 1 1 1 1 1 100%
10 Sample size 1 1 1 1 1 1 1 1 100%
11 Allocation of animals to experimental groups, randomization 0 1 1 1 1 1 1 0 75%
12 Experimental results 1 1 1 1 1 1 1 1 100%
13 Statistical analysis 1 1 1 1 1 1 1 1 100%
Results
14 Baseline, animal health status 1 1 1 1 1 1 1 1 100%
15 Number of animals analyzed, reasons for exclusion 0 0 0 0 0 0 0 0 0
16 Results and estimation, results for each analysis 1 1 1 1 1 1 1 1 100%
17 Adverse events 0 0 0 0 0 0 0 0 0
Discussion
18 Interpretation, scientific implications, study limitations 1 1 1 1 1 1 1 1 100%
19 Generalization and translation, relevance to human biology 1 1 1 1 1 1 1 1 100%
20 Sources of financing, conflict of interest 1 1 1 1 1 1 1 1 100%
Total score 16 18 18 18 16 18 18 17 19.37
Legend: Criteria classified as “0” (not reported) or “1” (reported).
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Effect of bisphosphonate use on orthodontic tooth mov ement: a systematic re view
Lessa GRG et al. Effect of bisphosphonate use on orthodontic tooth movement:
a systematic review
Table III - Methodological characteristics of included studies
Author/year,
country Animal/Sex Age Sample
size Study groups
Franzonietal., 2017
[16] (Brazil)
Male
Wistar Rats 70 days 16
Group 1: Orthodontic movement and administration of alendronate
sodium for 10 days; Group 2: Orthodontic movement and zoledronic
acid for 10 days; Control group: Orthodontic movement and saline
solution.
Seifietal.,
2017 [17] (Iran)
Male Wistar
Rats 56 days 30
Group 1: Negative control (rats that did not receive orthodontic
appliance); Group 2: Positive control group: rats receiving
orthodontic appliances and 0.01 cc of 0.9% sodium chloride
injectable solution; Group ZA: (Orthodontic appliance and 0.02 mg
of ZA diluted in 0.9% sodium chloride injectable solution).
Nakašetal., 2017
[18] (USA)
Male Wistar
Rats
56 to 63
days 60
Group E1: application of 10 mMol clodronate; Group E2: application
of 2.5 mMol of clodronate; Group E3: application of 10 mMol
clodronate; Group E4: application of 2.5 mMol of clodronate.
Brunetetal., 2016
[8] (Brazil)
Male Wistar
Rats 63 days 120
Control group: Orthodontic movement only; Control group without
movement: animals that did not receive drugs or orthodontic
movement; Zoledronic acid control group: animals receiving a single
dose (0.1 mg/kg) of zoledronic acid without orthodontic movement;
Experimental group zoledronic acid: animals given a single dose
(0.1 mg/kg) of zoledronic acid.
Salazaretal., 2015
[7] (Brazil)
Female Wistar
Rats 56 days 48
OVX group: ovariectomized rats; Group OVX + ALN1; Rats
ovariectomized and treated with Sodium Alendronate at 1 mg/
kg; Group OVX + ALN2: ovariectomized and treated with Sodium
Alendronate at 2 mg/kg; Control Group: Rats with simulated
operation.
Kaipaturetal., 2013
[19] (Canada)
Female Sprague
Dawley Rats 48 days 20
Group 1: (Control Group) - 5 rats that received only saline solution;
Group 2: (bisphosphonate group) - 0.015 mg of bisphosphonate
and 8 weeks of orthodontic movement. Group 3: (Saline group plus
orthodontic movement) - Saline solution and orthodontic movement
for 8 weeks; Group 4 (bisphosphonate group 2) - 0.015 mg of
bisphosphonate administered 12 weeks before and during the 8
weeks of orthodontic movement.
Karrasetal., 2009
[20] (USA)
Male Sprague
Dawley Rats 49 days 26
Experimental group: Rats were given 7 mg/kg body weight of
Sodium Alendronate; Control group: Rats which did not receive
treatment.
Liuetal.,
2004 [21] (Japan)
Male Wistar
Rats 63 days 120 Control group: Saline solution; Experimental group: 2.5, 10 and
40 mM Alendronate solution.
Table IV - Characteristics related to bisphosphonates and orthodontic tooth movement
Author/year, country Bisphosphonate dosage and
administration route
Time of
bisphosphonate use
Force applied during
orthodontic movement
Franzonietal., 2017 [16] (Brazil)
2.5 mg/kg of subcutaneous sodium
alendronate and
0.1 mg/kg of zoledronic acid
10 days 40c N
Seifietal. 2017 [17] (Iran) 0.02 mg zolena Alendronate the
mesio-vestibular root of PMS 21 days Light force
Nakašetal., 2017 [18] (USA)
10 mMol of clodronate and
2.5 mMol of clodronate injected into
the subperiosteal area adjacent to
the right maxillary incisor.
3 and 7 days Not informed
Brunetetal., 2016 [8] (Brazil) (0.1 mg/kg) of intraperitoneal
zoledronic acid
Single dose
(One week before experiment) 30 cN
Salazaretal., 2015 [7] (Brazil) 1 mg/kg and 2 mg/kg 90 days 50 cN
Kaipaturetal., 2013 [19] (Canada) 0.015 mg/kg subcutaneously 56 days 50 g
Karrasetal., 2009 [20] (USA) 7 mg/kg of body weight of Sodium
Alendronate 35 days 50 g
Liu et al al., 2004 [21] (Japan) 2.5,10 and 40 Mm injected into the
subperiosteum 21 days 120 mN
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Lessa GRG et al.
Effect of bisphosphonate use on orthodontic tooth mov ement: a systematic re view
Lessa GRG et al. Effect of bisphosphonate use on orthodontic tooth movement:
a systematic review
with orthodontic treatment influence such
events, reducing tooth movement and delaying
orthodontic treatment [23,24].
Most of the studies included in this
systematic review [7,16,18-21] agreed that the
systemic use of bisphosphonates contributed to
decrease orthodontic movement. Only the studies
by Seifi et al. (2017) [17] and Brunet et al.
(2016) [8] disagreed with this negative effect
of bisphosphonates, concluding that these drugs
did not interfere in the tooth movement process.
However, despite not having observed the
inuence of using bisphosphonate on orthodontic
movement, Sei et al. (2017) [17] found that
experimental bisphosphonate significantly
inhibited the bone and root resorption in rats,
assigning a protective and also benecial tissue
effect to this drug.
For Karras et al. (2009) [20], the inhibitory
effect of bisphosphonates on orthodontic movement
can be attributed to disrupting osteoclast function
and maintaining the compression sites of the
periodontal ligament, where bone resorption
becomes necessary for tooth movement to occur.
Table V - Characteristics related to the experiments
Author/year,
country
Experimental
unit Evaluated parameters Types of analysis
Franzonietal.,
2017 [16] (Brazil)
First molar and
third molar
upper left,
Maxilla
1. Amount of orthodontic movement; 1. Distance between the distal of the third
molar and mesial of the first molar on the left
side, measured with digital caliper;
2. Number of blood vessels and fibroblasts;
3. Number of osteoclasts; 2. Toluidine blue staining method;
4. Number of inflammatory cells. 3. Toluidine blue staining method;
4. Dominici staining method.
Seifietal.,
2017 [17] (Iran)
First molar and
second molar
upper left,
maxilla
1. Degree of orthodontic movement; 1. Distance between second and first molars
using slide gauge;
2. Number of blood vessels, osteoblast-like
cells and roots resorptive gaps (number and
area). 2. Hematoxylin and light microscope.
Nakašetal.,
2017 [18] (USA)
Upper incisor,
first molar on
both sides and
maxilla
1. Amount of orthodontic movement.
1. Distance between the incisors (middle of the
distoproximal surface of the incisors at 2 mm
(of the gums) and the molars (the middle of the
mesioproximal ridge of the first molar).
Brunetetal.,
2016 [8] (Brazil)
First upper
right molar and
upper central
incisor on the
same side,
maxilla
1. Amount of orthodontic movement;
1. Digital caliper positioned at the most cervical
point of the tooth measuring the mesial of the
first molar to the upper central incisor of the
left side by palatine;
2. Quantity of osteoclasts; 2. TRAP staining;
3. Expression of mature and immature collagen; 3. Picrosirius;
4. HE.
4. Presence of hyaline areas and root
resorption.
Salazaretal.,
2015 [7] (Brazil)
First and
second molars
upper right and
maxillary
1. Degree of orthodontic movement;
1. Images of the cuts of the first and second
molars were captured with an objective of
measuring the smallest distance between the
distal face of the first molar and the mesial face
of the second molar;
2. Quantification of alveolar bone tissue.
2. Slide histology were captured with an
objective. The bone located between the mesial
and distal root of the first maxillary molar was
selected for analysis.
Kaipaturetal.,
2013 [19]
(Canada)
First and
second molars
upper right and
maxilla
1. Degree of orthodontic movement; 1. Microscope and Optimas software (Media
Cybernetics, Newburyport, Mass);
2. Bone renewal rate. 2. Subtherapeutic levels of elemental strontium.
Karrasetal.,
2009 [20] (USA)
First molar and
second molar
maxilla
1. Degree of orthodontic movement. 1. Distance between second and first molars
using a microscope.
1. Amount of orthodontic movement;
Liuetal.,
2004 [21] (Japan)
First and
second molars,
maxilla
2. Osteoclast count.
1. Distance between first and second molars
using profile and tracking projector;
2. Trap method.
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Lessa GRG et al.
Effect of bisphosphonate use on orthodontic tooth mov ement: a systematic re view
Lessa GRG et al. Effect of bisphosphonate use on orthodontic tooth movement:
a systematic review
These authors came to this conclusion because
they veried that the drug reduced the osteoclasts
osteo-resorptive activity when evaluating the
effect of alendronate (bisphosphonate type) on
the induced tooth movement in rats, resulting in
smaller and slower orthodontic movement.
The difference between the ndings of some
experiments regarding the extent and speed of tooth
movement can be attributed to methodological
divergences, which seem to have significantly
inuenced the results. The main variations observed
in the methodologies of these studies were related
to the usage time of bisphosphonates, which
varied between single dose and 90 days of use,
and the sample size, varying between 16 and
120 rats [8,21]. Such variations ended up making
a real comparison extremely difcult between the
experimental results.
Variations in the drug dose also exerted an
inuence on the results of the studies analyzed,
with larger doses associated with smaller and
slower orthodontic movements, and smaller doses
Table VI - Main results and conclusions of the analyzed studies
Author
(year, country) Results Conclusion
Franzonietal., 2017 [16]
(Brazil)
A reduction of 58.3% in orthodontic movement was
observed in the OTM + A Group and 99.6% in the
OTM + Z Group when compared to the OTM Group.
There was a significant decrease in osteoclast and
inflammatory cells in BP treated groups. Blood
vessels and fibroblast cells decreased, mainly in the
group OTM + Z.
Sodium alendronate and zoledronic acid have similar
effects on periodontal tissue during orthodontic
treatment in rats. Zoledronic acid may especially
reduce orthodontic movement.
Seifietal., 2017 [17]
(Iran)
There were no significant differences in orthodontic
movement between the groups of applied force.
ZA significantly inhibited bone/root resorption and
angiogenesis compared to the positive control group.
Zolena did not decrease orthodontic movement, but
significantly inhibited bone and root resorption .
Nakašetal., 2017 [18]
(USA)
In the 7-day interval application regimen, decreased
tooth movement was observed with 10 mMol
compared to the 2.5 mMol clodronate concentration.
However, decreased tooth movement was also
observed when 2.5 mMol of clodronate was applied
at intervals of 7 versus 3 days. On the other hand, no
difference was observed when the concentration of
10 mMol was applied at intervals of 3 to 7 days.
Tooth movement decreases when clodronate
is applied subperiosteally in the root area. The
tooth movement is impeded by the higher dose of
clodronate, as well as by the shorter application
interval, even with lower dosage.
Brunetetal., 2016 [8]
(Brazil)
A lower number of osteoclasts and a higher
percentage of hyaline area were observed in the EAZ
group.
There was no difference between the groups
regarding bone remodeling, root resorption and tooth
movement at all observed times.
Salazaretal., 2015 [7]
(Brazil)
Intragroup comparisons showed significant
movement after five and seven days (p <0.05) for all
groups. The comparison between the groups revealed
greater tooth movement in the OVX Group (p <0.05)
on day 7.
Both doses of Sodium Alendronate similarly
decreased tooth movement in ovariectomized rats
(p> 0.05). The movement in the ovariectomized
groups + alendronate was also lower than the
non-ovariectomized groups, but with no statistical
difference.
Kaipaturetal., 2013 [19]
(Canada)
Both treatment groups with bisphosphonates
exhibited reduced tooth movement compared to
controls. The bisphosphonate dosage resulted in
reductions of 56% and 65% in dental protraction at 4
weeks and 8 weeks, respectively.
The study provided evidence that bone load from
the use of bisphosphonates may inhibit orthodontic
tooth movement .
Karrasetal., 2009 [20]
(USA)
Statistical analysis with repeated-measures analysis
of variance showed less orthodontic tooth movement
in the alendronate group compared with control
group (0.06 vs 0.24 mm at 2 weeks, and 0.45 vs 1.06
mm at 4 weeks; P = 0.0004 for the alendronate vs
control main effect).
This study demonstrated an inhibitory effect of
alendronate administration on orthodontic tooth
movement in a rat model.
Liuetal., 2004 [21]
(Japan)
Local injection of clodronate caused a significant
(P < 0.001) and dose-dependent reduction in tooth
movement in the rats. The number of osteoclasts on
the clodronate-injected side was significantly less
(P < 0.01) than on the control side. Local clodronate
also inhibited root resorption incident to tooth
movement.
These results suggest that localized use of
clodronate could be a useful therapeutic adjunct in
orthodontic treatment.
9
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Lessa GRG et al.
Effect of bisphosphonate use on orthodontic tooth mov ement: a systematic re view
Lessa GRG et al. Effect of bisphosphonate use on orthodontic tooth movement:
a systematic review
associated with larger and faster movements.
Corroborating with this statement in investigating
the effects of local application of 10mMol
bisphosphonate concentrations and 2.5mMol of
clodronate on tooth movement at 3- and 7-day
intervals, Nakaš et al. (2017) [18] observed
that the higher dose of clodronate resulted in a
substantially smaller and slower tooth movement.
The magnitude of the forces applied in the
studies also varied between 30 and 120 N, resulting
in different extensions and speeds of orthodontic
movements. Considering that the NiTi spring has the
ability to release a force with constant magnitude
without declining regardless of the elongation
performed, and that heavy forces in rats can cause
hyalinization and movement retardation, according
to Ren et al. (2004) [25], the ideal for investigation
of tooth movement in rats would be to apply a
force of less than 10 cN, which may be particularly
determinant for analyzing periodontal responses
and/or root resorption assessments [25-27].
Another relevant factor is the sex of the animal.
Experiments were performed on male rats in most
of the studies included in this review. However,
female and ovariectomized rats were used in the
studies by Salazar et al. (2015) [7], Kaipatur et al.
(2013) [19] and Mohammed and Kaklamanos
(2021) [28]. These variables should always be
considered when comparing results, since the rats
present similar behavior to that of postmenopausal
women under hormonal conditions, during which
they are more prone to osteoporosis and show
greater bone remodeling [29].
Although the studies of this review have
sometimes shown divergent results, the tools
used for their methodological evaluation revealed
a low risk of bias even though four information
details were not included by the authors;
additionally, a frequency of 19.37 was found
in the methodological quality, indicating good
qualication of the selected studies.
An important limitation of the analyzed
studies is that none of them used computerized
microtomography (micro-CT) to analyze orthodontic
movement. Using micro-CT enables an analysis of
several microtomographic planes/sections and
the internal three-dimensional visualization of the
study material, therefore representing an important
resource to offer more reliability to the studies and
thus enabling highly accurate and non-destructive
data analysis [30]. Another limitation of the
analyzed studies was the lack of use of anchoring
devices. Only the study by Kaipatur et al. [24]
used this device to facilitate orthodontic movement
in rats. The purpose of this device is to avoid
undesirable reactions and relapses after orthodontic
tooth movement. Within this context, it is suggested
to carry out more complete additional studies which
advance to overcome these limitations in order to
bring more reliable results regarding orthodontic
treatment.
Although orthodontic treatment is mainly
performed on adolescents, an increasing number
of adults have sought such treatment. A study by
Keim et al. [31] showed that adults comprise 20%
of all orthodontic patients, and that number has
increased even more in recent years. Considering
that bisphosphonates are mainly used by adults
and older adults, and that these drugs seem
to interfere with orthodontic movement, this
paradigm shift points to an increase in the number
of adults undergoing orthodontic treatment, and
therefore requires a better understanding of the
systemic usage effect of bisphosphonates during
this treatment.
CONCLUSION
Most studies of this systematic review point to
the fact that the systemic use of bisphosphonates
during orthodontic treatment seems to reduce
the extent and speed of tooth movement, thus
extending the treatment duration.
Author’s Contributions
GRGL, HSGP: Data Curation. MCM:
Conceptualization. MCM: Methodology. GRGL:
Writing – Original Draft Preparation. GRGL:
Writing – Review & Editing. ECL, RDAUL:
Visualization. HSGP: Software. HSGP: Validation.
ECL, RDAUL: Supervision. HSGP: Formal
Analysis. HSGP: Investigation. HSGP: Resources.
ECL, RDAUL: Project Administration and Funding
Acquisition.
Conicts of Interest
The authors declare no conict of interest.
Funding
This research did not receive any specic
grant from funding agencies in the public,
commercial, or not-for-prot sectors.
10
Braz Dent Sci 2024 Oct/Dec;27 (4): e4374
Lessa GRG et al.
Effect of bisphosphonate use on orthodontic tooth mov ement: a systematic re view
Lessa GRG et al. Effect of bisphosphonate use on orthodontic tooth movement:
a systematic review
Regulatory Statement
Not applicable considering this is a review
paper.
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Eloísa Cesário Fernandes
(Corresponding address)
Universidade Federal do Rio Grande do Norte, Departamento de Odontologia,
Natal, Rio Grande do Norte, Brasil.
E-mail: ecesariof@gmail.com
Date submitted: 2024 May 14
Accept submission: 2024 Oct 16