Effectiveness of biologic methods of inhibiting orthodontic tooth movement in animal studies

Introduction

A number of biologic methods leading to decreased rates of orthodontic tooth movement (OTM) can be found in the recent literature. The aim of this systematic review was to provide an overview of biologic methods and their effects on OTM inhibition.

Methods

An electronic search was performed up to January 2016. Two researchers independently selected the studies (kappa index, 0.8) using the selection criteria established in the PRISMA statement. The methodologic quality of the articles was assessed objectively according to the Methodological Index for Non-Randomized Studies scale.

Results

We retrieved 861 articles in the initial electronic search, and 57 were finally analyzed. Three biologic techniques were identified as reducing the rate of OTM: chemical methods, low-level laser therapy, and gene therapy. When the experimental objective was to slow down OTM, pharmacologic modulation was the most frequently described method (53 articles). Rats were the most frequent model (38 of 57 articles), followed by mice (9 of 57), rabbits (4 of 57), guinea pigs (2 of 57), dogs (2 of 57), cats (1 of 57), and monkeys (1 of 57). The sample sizes seldom exceeded 25 subjects per group (6 of 57 articles). The application protocols, quality, and effectiveness of the different biologic methods in reducing OTM varied widely.

Conclusions

OTM inhibition was experimentally tested with various biologic methods that were notably effective at bench scale, although their clinical applicability to humans was rarely tested further. Rigorous randomized clinical trials are therefore needed to allow the orthodontist to improve the effect of translating them from bench to clinic.

Highlights

  • Biologic methods can inhibit the rate of orthodontic tooth movement (OTM).

  • This systematic review examined the effects of biologic methods on OTM inhibition.

  • Chemical methods, low-level laser therapy, and gene therapy reduce the rate of OTM.

  • Pharmacologic modulation was the most frequently described method (53 articles).

Absolute control over tooth movement is a key factor in orthodontics. One main remaining limitation of past and current orthodontic treatments is the inability to completely prevent the unexpected movement of certain teeth; this is frequently defined as loss of anchorage during treatment or relapse during the retention phase. At present, auxiliary devices such as temporary anchorage devices are used to provide additional biomechanical resistance and help prevent undesirable tooth movement. Similarly, in recent decades, a number of biologic methods have emerged that can decrease the rate of orthodontic tooth movement (OTM) or even inhibit it completely by interfering with osteoclast cell activity during the bone remodeling on which OTM depends.

In this respect, chemical methods, including hormones, drugs, and various synthetic molecules, have been used from the earliest to the most recent studies on OTM. Bisphosphonates (inhibitors of bone resorption) and prostaglandin inhibitors, such as ibuprofen and acetylsalicylic acid, have been widely studied because of their activity in slowing OTM. Apart from the administration of specific drugs, other methods proposed in the literature to reduce the rate of OTM include processes that modify the biologic substrate, such as low-level laser therapy or gene therapy. The doses, protocols, and hypotheses are as varied as the studies themselves; this makes it difficult for the clinician to establish useful comparisons between studies and their relevance, if any, to the clinical field.

The purposes of this review were (1) to compile, analyze, and summarize the data available in the literature regarding experimental studies in animals that used biologic methods against a control group that resulted in a decreased rate of OTM or its inhibition; (2) to compare the different methods and their outcomes; and (3) to give the clinician a clear overview of the scientific evidence available in the literature with a quality analysis of the methodologies used in the articles reviewed, thus facilitating research for professionals with an interest in this area. The main specific questions asked in this review were the following: Which experimental biologic methods have a decreasing or inhibitory effect on OTM? How efficient are these methods?

Material and methods

Protocol

The structure of the review protocol was developed before the start of the study, and the reporting of findings followed the PRISMA guidelines ( www.prisma-statement.org ). Because the experimental studies on which this systematic review was based were on animals, our protocol could not be registered in the PROSPERO database.

Information resources

A search was made of the MedLine (Entrez PubMed, www.ncbi.nim.nih.gov ), SCOPUS ( www.scopus.com ), and Web of Science ( www.isiknowledge.com ) databases to find possible studies matching our established selection criteria, including all articles published up to January 21, 2016. We searched for gray literature by exploring the OpenGrey database, European Association for Grey Literature Exploitation, also up to January 21, 2016, without applying language restrictions.

Search strategy

Our search strategy used the medical subject heading term “tooth movement” crossed with “inhibition,” “inhibit,” or “decrease” and excluded the terms “relapse” or “increase” or “enhance” or “promotion.” Supplementary Table I summarizes the full search strategy, including animal search filters, in all databases used. Some main orthodontic journals not indexed in the Journal Citation Report index were also hand searched to identify potential studies not found in the electronic search ( Supplementary Table I ).

Eligibility

Articles selected for this study fulfilled the following criteria for inclusion, according to the PICOS format.

  • 1.

    Population: animals; any experimental study or clinical investigation that included at least 1 experimental group with a minimum of 5 animals or samples per group.

  • 2.

    Intervention: biologic methods of decreasing or inhibiting tooth movement using orthodontic or orthopedic devices to apply forces.

  • 3.

    Comparison: control group without a biologic method.

  • 4.

    Outcome: rate of OTM deceleration or inhibition.

  • 5.

    Study design: experimental controlled trials.

Excluded from the selection were case reports, case series, descriptive studies, review articles, opinion articles, letters, and articles that did not correspond to the objectives of this review or did not have an adequate description of the technique or the administration dose.

Study selection

Eligibility was assessed by 2 observers (M.C-P. and R.M.Y-V.) acting independently. Articles were initially selected on the basis of the title and abstract, with the complete article reviewed whenever there was doubt about whether it should be included. Disagreements were resolved by consensus or by a third experienced reviewer who was requested to arbitrate (A.I-L.). After the 2 reviewers had separately applied the inclusion and exclusion criteria to each article, concordance between them was measured using the kappa index.

Data collection and analysis

Data were extracted by 1 observer (M.C-P.). A data extraction sheet was developed and piloted. Conflicts during data collection were resolved by discussion with a second (R.M.Y-V.) or a third experienced observer (A.I-L.). Data were extracted for the following items: author and year, study design, sample (size, species, age, and sex), a brief description of the methods, applied force, total treatment or experimentation time, decrease in the rate of OTM, and clinical applicability.

Methodologic quality and risk of bias of individual studies

The methodologic quality of the selected articles was assessed using the Methodological Index for Non-Randomized Studies (MINORS). The 12 variables analyzed were clearly stated: aim, inclusion of consecutive patients, prospective collection of data, end points appropriate to the aim of the study, unbiased assessment of the study end point, follow-up period appropriate to the aim of the study, loss to follow-up less than 5%, prospective calculation of the study size, adequate control group, contemporary groups, baseline equivalence of the groups, and adequate statistical analysis. After this analysis, every item scored 0 when not reported, 1 when it was reported but inadequate, and 2 when it was reported and adequate. Articles obtaining between 0 and 7 points were assessed as low quality and therefore had a high risk of bias; studies with 8 to 15 points were considered as medium quality and with a medium risk of bias; and articles obtaining 16 to 24 points were classed as high quality and with a low risk of bias.

Results

Study selection

Two independent observers selected the studies, and good concordance was shown (kappa index, 0.8). A complete flow diagram of the search is given in the Figure .

Fig
PRISMA flow diagram.

Study characteristics and quality assessment

Rats were the most frequently used models in the sample (38 of 57 articles: 25 Wistar, 13 Sprague Dawley), followed by mice (9 of 57) and rabbits (4 of 57); guinea pigs and dogs were used in 2 articles each, and cats and monkeys in 1 each. The sample sizes seldom exceeded 25 subjects per group (6 of 57 articles). Randomization of the samples was mentioned in 24 articles, and blinding measures were found in only 14 studies ( Table I ).

Table I
Methodological quality of the selected articles with the Methodological Index for Nonrandomized Studies (MINORS)
Authors, year Clearly stated aim Inclusion of consecutive sample Prospective collection of data End points appropriate to aim of study Unbiased assessment of study end point Follow-up period appropriate to aim of study Loss to follow-up less than 5% Prospective calculation of study size Adequate control group Contemporary groups Baseline equivalence Adequate statistical analysis Total Q B
Chemical methods
Olteanu et al, 2015 2 2 2 2 0 2 0 0 2 0 0 2 14 M M
Kanzaki et al, 2015 2 2 2 2 0 2 0 0 2 0 0 1 13 M M
Hakami et al, 2015 2 2 2 2 0 2 0 0 2 0 0 2 14 M M
Fernandez-González et al, 2015 2 2 2 2 0 2 0 2 2 2 2 2 20 H L
Venkataramana et al, 2014b 2 2 2 2 0 2 0 0 2 0 0 1 13 M M
Venkataramana et al, 2014a 2 2 2 2 0 2 0 0 2 0 0 1 13 M M
Oliveira et al, 2014 2 2 2 2 1 2 0 0 2 2 0 1 16 H L
Nagaie et al, 2014 2 0 2 2 0 2 0 0 1 2 1 1 13 M M
Toro et al, 2013 2 0 2 2 1 2 0 0 2 2 0 1 14 M M
Kaipatur et al, 2013 2 2 2 2 1 2 1 0 2 2 1 1 18 H L
Yabumoto et al, 2013 2 2 2 2 0 1 0 0 2 2 0 1 14 M M
Olyaee et al, 2013 2 2 2 2 0 2 0 0 2 2 0 2 16 H L
Sodagar et al, 2013 2 2 2 2 0 2 0 0 2 2 0 1 15 M M
Kondo et al, 2013 2 2 2 2 0 2 0 0 1 2 0 1 14 M M
Esfahani et al, 2013 2 2 2 2 0 1 0 0 2 2 0 1 14 M M
Yoshimatsu et al, 2012 2 2 2 2 1 2 0 0 2 2 0 1 16 H L
Kohara et al, 2012 2 1 2 2 0 2 0 0 1 2 0 1 13 M M
Hammad et al, 2012 2 2 2 2 0 2 0 0 2 0 0 1 13 M M
Meh et al, 2011 2 2 2 2 0 2 0 0 2 2 0 1 15 M M
Hao and Hua, 2011 2 2 2 2 1 2 0 0 2 2 0 1 16 H L
Gonzales et al, 2011 2 2 2 2 0 2 0 0 2 2 0 1 15 M M
Shoji et al, 2010 2 2 2 2 0 1 0 0 2 0 0 2 13 M M
Santos et al, 2010 2 2 2 2 1 2 0 0 2 2 0 1 16 H L
Han et al, 2010 2 2 2 2 0 2 0 0 2 2 0 1 15 M M
Choi et al, 2010 2 2 2 2 0 2 0 0 2 2 0 1 15 M M
Baysal et al, 2010 2 2 2 2 0 2 0 0 2 2 0 2 16 H L
Akhoundi et al, 2010 2 2 2 2 0 2 0 0 2 2 0 1 15 M M
Karras et al, 2009 2 2 2 2 0 2 1 0 2 2 0 1 16 H L
Fujimura et al, 2009 2 1 2 2 0 2 0 0 2 2 0 1 14 M M
Sprogar et al, 2008 2 2 2 2 0 2 0 0 2 2 0 2 16 H L
Kriznar et al, 2008 2 2 2 2 0 2 0 0 2 2 0 2 16 H L
Kitaura et al, 2008 2 2 2 2 0 2 0 0 2 2 0 2 16 H L
Hauber Gameiro et al, 2008 2 2 2 2 1 2 0 0 2 2 0 1 16 H L
Sprogar et al, 2007 2 2 2 2 0 2 0 0 2 2 0 1 15 M M
Keles et al, 2007 2 2 2 2 0 1 0 0 2 2 0 1 14 M M
Dunn et al, 2007 2 2 2 2 0 2 1 0 2 2 0 1 16 H L
de Carlos et al, 2007 2 2 2 2 1 1 0 1 2 2 0 2 17 H L
Bildt et al, 2007 2 2 2 2 0 2 0 0 2 2 0 2 16 H L
de Carlos et al, 2006 2 2 2 2 1 1 0 0 2 2 0 2 16 H L
Arias and Marquez-Orozco, 2006 2 2 2 2 1 1 0 0 2 2 0 1 15 M M
Jäger et al, 2005 2 2 2 2 1 2 0 0 2 2 0 2 17 H L
Liu et al, 2004 2 2 2 2 0 2 0 0 2 2 0 1 15 M M
Gurton et al, 2004 2 2 2 2 0 1 0 0 2 2 0 2 15 M M
Shirazi et al, 2002 2 2 2 2 0 2 0 0 2 2 0 2 16 H L
Zhou et al, 1997 2 2 2 2 0 1 0 1 2 2 0 1 15 M M
Karsten and Hellsing, 1997 2 2 2 2 1 2 0 1 2 2 0 2 18 H L
Kehoe et al, 1996 2 2 2 2 0 1 0 0 2 1 0 1 13 M M
Igarashi et al, 1994 2 2 2 2 1 2 0 0 2 2 0 1 16 H L
Wong et al, 1992 2 2 2 2 0 2 0 0 1 2 0 0 13 M M
Hellsing and Hammarstrom, 1991 2 2 2 2 1 2 0 1 2 2 0 2 18 H L
Mohammed et al, 1989 2 2 2 2 0 2 0 0 2 2 0 1 16 H L
Chumbley and Tuncay, 1986 2 2 2 2 0 2 0 0 2 2 0 1 13 M M
Sandy and Harris, 1984 2 2 2 2 0 1 0 1 2 2 0 2 14 M M
Low-level laser therapy
Kim et al, 2015 2 2 2 2 1 2 0 0 2 2 0 1 16 H L
Kim et al, 2009 2 2 2 2 0 2 0 0 2 2 0 1 15 M M
Seifi et al, 2007 2 2 2 2 1 2 0 0 2 2 0 1 15 M M
Gene therapy
Kanzaki et al, 2004 2 2 2 2 1 2 2 0 2 2 0 1 16 H L
Q , Quality; B , risk of bias; H , high; L , low; M , medium.

The most commonly used biologic method leading to reduced orthodontic tooth movement was pharmacologic administration, and a wide range of substances were used (53 of 57 articles). The main substances evaluated in the selected articles were nonsteroidal anti-inflammatory drugs (NSAIDS) in 14 articles, followed by cytokines and bisphosphonates in 10 articles each. Three articles were based on antihistamines, and 2 articles each on hormones, fluoride, and beta blockers. Finally, 10 articles concentrated on other substances, such as immunosuppressants, morphine, nitric oxide, phenytoin, nicotine, simvastatin, endothelin, and tetracycline, or Nrf2 activators. Twenty-five studies were categorized as high quality with a low risk of bias (over 16 points), although on the 24-point scale used, no article scored more than 20 points. The remaining articles were considered to be medium quality.

Outcomes

The methods included in this review fall into 3 major categories: chemical or pharmacologic methods, gene therapy, and low-level laser therapy ( Table II ). Fifty-three of the 57 studies were classed as chemical methods. These comprised a wide range of substances, ranging from NSAIDs to bisphosphonates and cytokines, and were mainly administered in 1 of 2 forms: local or systemic. NSAIDS and other selective COX-2 inhibitors were the most frequently described substances (14 of 53 studies). Diclofenac seems to have the strongest inhibitory effect on OTM; de Carlos et al, in a study rated as high quality, described complete inhibition when diclofenac was used on rats under 100 and 50 g of force ( P <0.01), and partial inhibition with rofecoxib under 50 g of force ( P <0.01), although some movement was found (a reduction of approximately 70%) with rofecoxib and 100 g of force, compared with the controls ( P <0.05). In another article by the same authors, no statistically significant reduction in OTM was found with parecoxib or celecoxib compared with the controls at 50 g of force. However, short-term use of celecoxib slowed down OTM by 30% and long-term use by 46% ( P <0.01), as determined by a study of high methodologic quality, whereas in another, assessed as medium quality, 50% less tooth movement was found with the same drug ( P <0.01). However, a higher decrease in OTM was found by Hammad et al with paracetamol and ketorolac than with celecoxib ( P <0.01). Indomethacin obtained different results; it was reported to reduce the rate of OTM by half compared with the controls ( P <0.01), as described in a study rated as high quality, and to reduce OTM by 40% ( P <0.05) and 25% ( P <0.01) in 2 studies of medium methodologic quality. In the latter study, the prostaglandin (PG) analogs, prostacyclin (PGI2) and thromboxane A2 (TxA2), were compared with 2 PG inhibitors, indomethacin (a PGI2 inhibitor) and imidazole (a TxA2 inhibitor). The PG analogs—PGI2 much more than TxA2—significantly increased the rate of OTM in rats, whereas indomethacin and imidazole reduced OTM, with no significant differences in their inhibitory effects. Leukotriene inhibitors—and not only PG—were also reported to decrease OTM (application of AA861 resulted in 29.8% less OTM and 36% less tooth movement combined with indomethacin) ( P <0.05), as 1 high-quality study demonstrated ( Table II ).

Table II
Summary of articles included in the review
Authors, year Study design Sample (n) Description of groups Species Age, sex Force
(g)
Time (d) Decrease in rate of OTM Human clinical applicability
tested
Chemical methods
Olteanu et al, 2015 CS 24 G1) CG: OTM only; G2) 1.5 mL aspirin by gastric gavage + OTM; G3) 1.2 mL algocalmin by gastric gavage + OT WR NM, 24 M 25 28 Decrease of OTM with aspirin and algocalmin ( P = 0.0001) Yes
Kanzaki et al, 2015 CS 20 G1) CG: no OTM; G2) OTM + right hemi-maxilla: 2 μL intragingival SFN (Nrf2 activator) in DMF, left hemi-maxilla DMF only; G3) OTM + right hemi-maxilla: 2 μL intragingival EGCG (Nrf2 activator) in DMF, left hemi-maxilla DMF only Mi 6 wk, 20 M 10 21 60% less OTM compared with controls ( P <0.05) No
Hakami et al, 2015 CS 32 G1) CG: no OTM; G2) 1.5 μg/d intragingival IL-4 + OTM; G3) intragingival PBS + OTM; G4) 0.015 μg/d intragingival IL-4 + OTM; G5) 0.15 μg/d intragingival IL-4 + OTM Mi 10-12 wk, 32 M 10 12 Less OTM with 1.5 μg/d IL-4 but not with the rest of the doses ( P <0.01) No
Fernandez-González et al, 2015 CS 42 G1) CG: OTM only; G2: OTM + twice/w subgingival injections of 5 mg/kg OPG-Fc mesial and distal to maxillary first molar SDR 6 mo, 42 M 50 21 52%, 31%, and 22% less OTM at days 7, 14 ( P <0.01), and 21 ( P <0.05), respectively Yes
Venkataramana et al, 2014b CS 20 G1) CG: 1 mL IP saline solution + OTM; G2) 1.5 mg/kg IP pamidronate + OTM R 16 wk, 20 M 100 21 Less OTM with pamidronate ( P <0.05) Yes
Venkataramana et al, 2014a CS 20 G1) CG: 1 mL IP saline solution + OTM; G2) 0.3 mg/kg intragingival ibandronate + OTM R 16 wk, NM 100 21 Less OTM with ibandronate ( P <0.05) Yes
Oliveira et al, 2014 CS 20 G1) vehicle only; G2) OTM + vehicle; G3) OTM + 0.1 mg/kg/d oral propranolol; G4) OTM + 20 mg/kg/d oral propranolol WR 3 mo, 20 M 50 10 Low dose propranolol (0.1 mg/kg) reduced OTM by 41%; a higher dose did not ( P <0.05) No
Nagaie et al, 2014 CS 20 G1) CG, OTM + oral administration of basal pure water; G2) OTM + 13 μg/mL TSC water containing 1 μg/mL nicotine WR 13 wk, 20 M NM 10 28% less OTM with nicotine ( P <0.01) No
Toro et al, 2013 CS 30 G1) 2-wk SC injection vehicle then OTM; G2) 2-wk SC injections 25 mg/kg BE, then OTM; G3) 2-wk SC injections 1 mg/kg alendronate, then OTM SDR NM, 30 M 13 28 BE and alendronate reduced OTM by 64% and 84%, respectively ( P <0.05) No
Kaipatur et al, 2013 CS 20 G1) OTM + SC injection 0.015 mg/kg alendronate; G2) OTM + vehicle; G3) 3-mo alendronate, then OTM; G4) 3-mo vehicle, then OTM SDR 12 wk, 20 F 50 56 65% less OTM on G1/G2 ( P = 0.05), 86% less OTM on G3/G4 (prior intake bisphosphonates) ( P <0.01) No
Yabumoto et al, 2013 CS 80 G1) wild-type mice, OTM + saline solution; G2) wild-type mice, OTM + injection of 15 mg/kg IP reveromycin A; G3) OPG deficient KO mice, OTM + saline solution; G4) OPG deficient KO mice, OTM + 15 mg/kg IP reveromycin A Mi 8 wk, 80 M NM 3 NSRD after 3 days between groups No
Olyaee et al, 2013 CS 48 G1) OTM + 100 mg/kg/d ethinyl estradiol by gavage + 1 mg/kg/d norgestrel by gavage; G2) CG OTM + saline solution WR 12 wk, 48 F 30 14 39% less OTM with estradiol and norgestrel ( P <0.05) No
Sodagar et al, 2013 CS 28 G1) OTM only; G2) OTM + injection of 0.3 mg celecoxib SDR 5 wk, 28 M 60 18 50% less OTM ( P <0.01) No
Kondo et al, 2013 CS NM G1) 7-d IP injections 20 μg/g propranolol (β-antagonist) then OTM; G2) 7-d IP injections 5 μg/g isoproterenol (β-agonist) then OTM; G3) 7-d IP injections 0.9% saline solution, then OTM Mi 8 wk, M NM 5 β-antagonist decreased OTM by 35.7%; β-agonist increased it by 14.3% ( P <0.05) No
Esfahani et al, 2013 CS 32 G1) CG: OTM + saline solution; G2) OTM + 2.5 mg/kg IP simvastatin WR 8-10 wk, 32 M 60 17 Significantly less OTM ( P <0.024) No
Yoshimatsu et al, 2012 CS 32 G1) no OTM or injection (CG); G2) OTM + 0.015 mg/d IL-12; G3) OTM + 0.15 mg/d IL-12; G4) OTM + 1.5 mg/d IL-12 G5) OTM + PBS Mi 8 wk, 32 M 10 12 1.5 mg/d IL-12 significantly decreases OTM ( P <0.001); with lower doses, NSRD were found No
Kohara et al, 2012 CS NM G1) OTM + injections IFN-g (0.015-1.5 μg per 20 mL); G2) (CG) OTM + PBS Mi 8 wk, NM 10 12 61.4% less OTM in the group treated with interferon ( P <0.05) No
Hammad et al, 2012 CS 40 G1) CG: reverse osmosis water + OTM; G2) 10 mg/kg celecoxib + OTM; G3) 3 mg/kg ketorolac + OTM; G4) 150 mg/kg paracetamol + OTM. WR 12 wk, 40 M 50 60 celecoxib did not reduce OTM compared with ketorolac and paracetamol ( P <0.01) Yes
Meh et al, 2011 CS 48 G1) oral saline solution; G2) OTM + oral saline solution; G3) 3 mg/kg/d oral cetirizine + OTM SDR 13 wk, 48 M 25 42 cetirizine reduced OTM by 26.1% ( P <0.01) No
Hao and Hua, 2011 CS 72 G1) OTM + local injections of PBS (CG); G2, G3, G4) OTM and systemic injections of 0.16, 0.12, 0.08, and 0.04 mg/mL rhsTNF-RI. SDR 6 wk, 72 M 50 14 NSRD in the 0.04 mg/mL group, but 40% decrease in OTM in the rest of the groups ( P <0.01) No
Gonzales et al, 2011 CS 50 G1) no OTM, no NaF; G2) OTM, no NaF; G3) OTM + 2-wk 45 ppm oral NaF; G4) OTM + 4-wk 45 ppm oral NaF; G5) OTM + 12-wk 45 ppm oral NaF WR NM, 50 M 50 84 74% decrease in OTM ( P <0.01) Yes
Shoji et al, 2010 CS 48 in OPG -/- mice (a model for juvenile Paget disease): G1) CG: IP saline solution + OTM; G2) 1.25 mg/kg/d IP alendronate + OTM in wild-type mice; G3) CG: IP saline solution + OTM; G4) 1.25 mg/kg/d IP alendronate + OTM Mi 8 wk, 48 M NM 3 administration of alendronate to OPG -/- mice decreased OTM ( P <0.01) No
Santos et al, 2010 CS 120 G1) OTM + saline solution; G2) OTM + FK506; G3) FK506 only; G4) saline solution only WR 9 wk, 120 M 35 14 19% less OTM with tacrolimus immunosuppressant (FK506) treatment ( P <0.05) No
Han et al, 2010 CS 32 G1) 2.5 mg simvastatin per kg/d; G2) CG WR 7-8 wk, 32 M 50 49 45% less OTM ( P <0.001) Yes
Choi et al, 2010 CS 54 G1) 2.5 mM/L clodronate; G2) 10 mM/L clodronate; G3) CG WR 8 wk, 27 M/27 F 60 17 OTM reduced by 32% and 36.3%, respectively ( P <0.05) Yes
Baysal et al, 2010 CS 28 G1) no OTM; G2) OTM + thyroxine; G3) OTM + doxycycline; G4) OTM only WR 7-8 wk, 28 M 50 14 NSRD Yes
Akhoundi et al, 2010 CS 40 G1) OTM; G2) OTM + injections 5 mg/d morphine; G3) OTM + 5 mg/d morphine + 20 mg/d naltrexone; G4) OTM + 20 mg/d naltrexone/normal saline solution WR NM, 40 M 60 14 morphine reduced OTM by 52% ( P <0.05) No
Karras et al, 2009 CS 50 G1) CG, OTM only; G2) OTM + injections of alendronate sodium of 7 mg/kg body weight per week SDR NM, NM 50 35 42% less OTM in the alendronate group after 4 weeks ( P <0.001) No
Fujimur et al, 2009 CS NM G1) OTM + local bisphosphonate; G2) OTM + PBS Mi 8 wk, M NM 12 50% less OTM ( P <0.05) No
Sprogar et al, 2008 CS 34 G1) no OTM + saline solution; G2) OTM + saline solution; G3) OTM + 10 mg/kg IP famotidine WR NM, 34 M 25 42 significantly less OTM ( P <0.001) No
Kriznar et al, 2008 CS 34 G1) no OTM + saline solution; G2) OTM + saline solution; G3) OTM + 10 mg/kg IP cetirizine WR NM, 34 M 25 42 significantly less OTM ( P <0.05) No
Kitaura et al, 2008 CS NM G1) OTM + daily injection 10 μg anti-CFms antibody; G2) OTM + PBS Mi 8 wk, NM 10 12 anti-CFms antibody reduces OTM by in 36.7% ( P <0.05) No
Hauber Gameiro et al, 2008 CS 32 G1) OTM + IP injections celecoxib 3 d; G2) OTM + IP injections saline 3 d; G3) OTM + IP injections celecoxib 14 d; G4) OTM + IP injections control 14 d WR NM, 32 M 50 14 celecoxib decreases OTM by 30% with short-term dosage, and 46% with long-term dosage ( P <0.05) No
Sprogar et al, 2007 CS 30 G1) OTM + TBC3214; G2) OTM + placebo; G3) placebo WR 11-12 wk, 30 M 25 40 daily TBC3214, treatment reduces OTM by 33.3% ( P <0.001) No
Keles et al, 2007 CS 51 G1) OTM; G2) Pamidronate + OTM; G3) OPG + OTM Mo 8 wk, 51 M 22,4 12 pamidronate inhibited OTM by 34%, OPG by 77% ( P <0.01) Yes
Dunn et al, 2007 CS 30 G1) OTM + injection PBS; G2) OTM + 0.5 mg/kg local injections recombinant OPG; G3) OTM + 50 mg/kg local injections recombinant OPG WR NM, 30 M 54 21 OTM was inhibited by 70.6% after 14 days in higher-dose group ( P <0.001) and by 31.8% in lower-dose group ( P <0.05) No
de Carlos et al, 2007 CS 28 G1) OTM + rofecoxib; G2) OTM + celecoxib; G3) OTM + Ppecoxib; G4) control WR 12 wk, 28 M 50 5 rofecoxib inhibits OTM ( P <0.05); NSRD between parecoxib and celecoxib and controls Yes
Bildt et al, 2007 CS 18 G1) OTM + PBS injection; G2) OTM + injection 6 mg CMT-3/kg body weight; G3) OTM + injection 30 mg CMT-3/kg body weight WR NM, 18 M 10 14 CMT reduced OTM by 15.7% in 6-mg group and 34.3% in 30-mg group, respectively ( P <0.05) No
de Carlos et al, 2006 CS 42 G1) OTM (50 g) + rofecoxib; G2) OTM (50 g) + diclofenac; G3) control
G4) G5) G6) OTM (100 g) + same pharmacologic treatment as 1, 2, and 3
WR NM, 42 M 50-100 10 Diclofenac inhibits OTM under 50 and 100 g forces ( P <0.01); rofecoxib inhibits OTM under 50 g force ( P <0.01) and reduces it by 73.6% under 100 g force ( P <0.05) Yes
Arias and Marquez-Orozco, 2006 CS 36 G1) OTM + 100 mg/kg/d ASA; G2) OTM + 30 mg/kg/d ibuprofen; G3) OTM + 200 mg/kg/d acetaminophen; G4) CG: OTM + vehicle WR NM, 36 M 30 10 aspirin reduced OTM by 38.75% ( P <0.05), ibuprofen by 41.52% ( P <0.01); acetaminophen did not affect OTM Yes
Jäger et al, 2005 CS 80 G1) OTM + PBS; G2) OTM + sIL-1-R; G3) OTM + sTNF-a-RI; G4) OTM + both WR 12 wk, 80 M 50 12 60% less OTM ( P <0.05) No
Liu et al, 2004 CS 26 G1) OTM; G2) OTM + 2.5 mM clodronate; G3) OTM + 10 mM clodronate; G4) OTM + 40 mM clodronate WR 7 wk, 26 M 12 21 56%, 65%, and 81% less OTM, respectively ( P <0.001) No
Gurton et al, 2004 CS 150 G1) OTM + iloprost; G2) OTM + indomethacin; G3) OTM + U 46619; G4) OTM + imidazole; G5) OTM + 0.9% NaCl; G6) no OTM + NaCl; G7) no OTM or solution SDR NM 150 M 20 5 Pg analogs increase OTM by 31.28%
Pg antagonists reduce OTM by 20.26% ( P <0.01)
Yes
Shirazi et al, 2002 CS 48 G1) CG, no injections; G2) saline solution group; G3) 200 mg/kg injections of L-arg; G4) 10 mg/kg L-NAME group SDR NM, M 60 13 50% less OTM with the L-NAME group (reduced nitric oxide production led to a decrease in OTM) ( P <0.001) No
Zhou et al, 1997 CS 96 G1) OTM + subcutaneous indomethacin; G2) OTM + saline solution SDR 5-6 wk, 96 M 40 10 40% less OTM with indomethacin ( P <0.05) No
Karsten and Hellsing, 1997 CS 20 G1) OTM + phenytoin; G2) control SDR 3-5 mo, 20 F 15 42 not conclusive. No
Kehoe et al, 1996 CS 40 G1) CG: OTM + placebo; G2) 100 μg/kg/12-h misoprostol + OTM; G3) 200 mg/kg/12-h acetaminophen + OTM; G4) 30 mg/kg/12-h ibuprofen + OTM GP 6-8 wk, 40 M 25 11 acetaminophen showed NSRD with controls; ibuprofen reduced OTM by approximately 22% ( P <0.001) No
Igarashi et al, 1994 CS 77 G1) systemic AHBuBP (bisphosphonate) every 24 h + OTM; G2) OTM only; G3) topical AHBuBP + OTM WR 9-10 wk, 77 M 16.8 21 40% less OTM with systemic application, 70% less OTM with topical administration ( P <0.001) No
Wong et al, 1992 CS 11 G1) CG: OTM + sodium bicarbonate; G2) OTM + oral administration of 65 mg/kg/d ASA GP NM, NM 8 28 NSRD No
Hellsing and Hammarstrom, 1991 CS 16 G1) OTM in pregnant rats; G2) OTM in nonpregnant rats; G3) nonpregnant rats + NaF SDR 3-5 mo, 16 F 15 21 52% less OTM with NaF; 39% more OTM in pregnant rats ( P <0.01) No
Mohammed et al, 1989 CS 132 G1) OTM + leukotriene synthesis inhibitor; G2) OTM + indomethacin; G3) OTM; G4) OTM + both groups SDR NM, NM 60 14 29.8% less OTM with AA861 combined with indomethacin; 36.2% less OTM with indomethacin only ( P <0.05) No
Chumbley and Tuncay, 1986 CS 12 G1) OTM (CG); G2) OTM + oral administration of 5 mg/kg/d indomethacin C 12-18 mo, NM 250 21 indomethacin group achieved approximately 50% less than the CG ( P <0.01) No
Sandy and Harris, 1984 CS 14 G1) CG (OTM + vehicle of MC; G2) OTM + flurbiprofen R NM 7 F/7 M 100 14 NSRD No
Gene therapy
Kanzaki et al, 2004 CS 20 G1) CG, no OTM CG; G2) OTM + PBS; G3) OTM + injections of OPG gene transfer WR 6 wk, 20 M 17 20 92.8% less OTM ( P <0.001) Yes
Low-level laser therapy
Kim et al, 2015 CS 10 G1) CG: OTM alone; G2) OTM into the grafted defects; G3) OTM into the grafted defects + LLLT. D 18-24 mo, 10 M 100 42 LLLT decreased OTM into the bone-grafted surgical defects ( P <0.01) Yes
Kim et al, 2009 CS 12 G1) CG OTM only; G2) OTM + CO; G3) OTM + LLLT; G4) OTM + CO + LLLT D 84 wk, 12 M 150 56 LLLT after CO decreases OTM 48.4% ( P <0.001) No
Seifi et al, 2007 CS 18 G1) CG; G2) LLLT (850 nm); G3) LLLT (630 nm) R 16 wk, 18 M 10-120 16 Pulsed and continuous LLLT reduced OTM by 40.6% and 50.6% ( P <0.001) No
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Apr 4, 2017 | Posted by in Orthodontics | Comments Off on Effectiveness of biologic methods of inhibiting orthodontic tooth movement in animal studies
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