A randomized, placebo-controlled clinical trial on the effects of recombinant human relaxin on tooth movement and short-term stability.

INTRODUCTION: Moving teeth rapidly and avoiding posttreatment relapse are fundamental goals of orthodontic treatment. In-vitro and animal studies suggest that the human hormone relaxin might increase the rate of movement and the stability through its effect on the periodontal ligament. The purpose of this study was to compare relaxin and a placebo with regard to tooth movement and stability in human subjects. METHODS: A single-center, blinded, placebo-controlled, randomized clinical trial was used to examine the effect of relaxin on tooth movement and stability. Forty subjects were randomized 1:1 and received weekly injections of 50 µg of relaxin or a placebo for 8 weeks. Aligners programmed to move a target tooth 2 mm during treatment were dispensed at weeks 0, 2, 4, and 6. Movement was measured weekly on polyvinyl siloxane impressions that were scanned and digitized. The subjects were followed through week 12 to assess relapse. RESULTS: Tooth movement over the 8-week treatment period did not differ by treatment group (P = 0.995). By using an intent-to-treat analysis, we found that the mean tooth movement for both groups was 0.83 mm (SE, 0.08 for relaxin and 0.09 for the placebo). Relapse from weeks 8 to 12 was the same in both groups (P = 0.986), and the mean was -0.75 (SE, 0.07 for relaxin and 0.08 for theplacebo). CONCLUSIONS: No differences in tooth movement over 8 weeks of treatment or relapse at 4 weeks posttreatment were detected when comparing subjects who received weekly injections of relaxin with those who received a placebo. In both groups, an average of less than half of the programmed tooth movement was obtained after 8 weeks of treatment. The local doses of relaxin might have been too low to affect tooth movement or short-term relapse.

Use of relaxin in orthodontics.

BAS Medical is investigating the use of relaxin to improve ortho-dontic treatments. Relaxin is well known for its effects on remodeling soft tissue, and we believe relaxin will be clinically useful in speeding tooth movement and preventing relapse. We investigated the use of relaxin in preventing relapse in a dog model. Dog maxillary second incisors were orthodontically rotated an average of 42 degrees, and then relaxin was administered by gingival injection to relieve the rotational memory in the connective tissues. Teeth were retained for 30 days to allow fibers to reform. Teeth then were released and relapse was measured by a series of impressions. Animals receiving relaxin gingival injections (n = 8) were compared with placebo-treated animals (n = 8) (exhibiting high relapse) and gingival fiberotomies (n = 8) (low relapse). Gingival fiberotomy is a surgical procedure to cut the gingival connective tissues away from the tooth and has been shown to be effective in preventing relapse clinically and in animal models. There was a significant difference in relapse between the fiberotomy and the placebo control groups, and the relaxin-treated group had an intermediate response between the two groups (nonsignificant). Dose and treatment optimization may improve the response in future studies. To study the underlying mechanisms, we have localized relaxin receptors on gingival and periodontal ligament fibroblasts in tissue slices and cell cultures. Relaxin was found to stimulate collagenase production by relaxin in human gingival fibroblast cultures. Taken together, the data support a role for relaxin therapy to speed tooth movement and prevent relapse in orthodontic practice.

Efficacy of surgical and non-surgical interventions on accelerating orthodontic tooth movement: a systematic review.

PURPOSE: To conduct a systematic review of randomised controlled trials (RCTs) evaluating the effect of surgical and non-surgical procedures on the acceleration of orthodontic tooth movement (OTM) as an adjunct to orthodontic therapy (OT) in order to estimate the efficacy of these procedures and the benefit of their use in everyday orthodontic practice. MATERIALS AND METHODS: Literature search was performed on PubMed, Scopus, Web of Science and Cochrane databases up to July 2014. Inclusion criteria were: (1) RCTs; (2) orthodontic therapy on permanent dentition; (3) application of adjunctive surgical or non-surgical procedures for accelerating OTM; (4) measurement of tooth movement. The primary outcome measure was tooth movement expressed as cumulative tooth movement (CTM), rate of tooth movement (RTM) or time of tooth movement (TTM). Pain and discomfort, periodontal health, anchorage loss, bone and root changes, and undesired tooth movement were evaluated as secondary outcomes. RESULTS: Literature research identified 184 studies. After screening of titles, abstracts and full-text studies, fifteen fulfilled the inclusion criteria and were included in this review. Six of the included studies investigated the effect of corticotomies, one of interseptal bone reduction, four of lowlevel laser therapy (LLLT), three of intraoral/extraoral devices releasing extracorporeal shock waves (ESWT), pulsed electromagnetic field (PEMF) and electrical current, respectively, and one of injected substances (relaxin) as an adjunct to OT. Three studies resulted of high methodological quality, six of medium, and six of low quality. Interseptal bone reduction was reported to increase RTM during the first 2 months (P = 0.002) and CTM at 3 months (P = 0.003). Studies investigating corticotomy reported significantly increased RTM (up to 2.3 times) during the first months after intervention, whereas results on TTM and CTM were quite controversial ranging from non-significant to highly significant (up to three times of TTM increase). The heterogeneity between studies investigating corticotomy could not allow for quantitative synthesis of the findings. Out of four studies investigating LLLT three reported positive effect on OT. Due to inadequate statistical analysis of data from original articles, results could not be summarised in meta-analyses. Effects of both electrical current devices and PEMF devices on CTM were reported to be larger on the experimental sides than on the control sides (P < 0.001). The other interventions were reported to be of no statistical or clinical relevance. CONCLUSIONS: In the short term, corticotomy can accelerate OTM whereas long-term effects are questionable, thus no firm conclusions can be made on its efficacy and benefit of clinical use. There is some evidence that LLLT can slightly accelerate OTM but this result is not significant and the effect estimated is not clinically relevant. The very limited research-based evidence suggesting beneficial effects of interseptal bone reduction, electrical current and PEMF on OTM does not allow for solid conclusions. More high quality clinical research is required in order to estimate the efficacy of adjunctive interventions on accelerating OTM and their potential clinical use.

Preventive and therapeutic effects of relaxin on bisphosphonate related osteonecrosis of the jaw: an experimental study in rats / Efeitos preventivos e terapêuticos da relaxina na osteonecrose da mandíbula relacionada a bisfosfonatos: um estudo experimental em ratos

Objective: Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a challenging complication of chronic bisphosphonate (BP) use. The hormone relaxin is able to induce the multistep differentiation process of human osteoclastogenesis, exhibits antifibrotic and anti-inflammatory actions, and promotes vasodilatation, wound healing, and angiogenesis. The present study aimed to evaluate the effects of relaxin in the prevention and management of BRONJ. Material and Methods: Thirty-six male Sprague Dawley rats were randomly divided into four groups. Rats in group 1 (n = 10) received relaxin and BP simultaneously for 12 weeks. Rats in group 2 (n = 10) received injections of BP for 12 weeks, followed by relaxin for another 12 weeks. Rats in group 3 (n = 10) received only BP injections, and those in group 4 (control, n = 6) received only saline. Necrosis and inflammation in the rats' mandibles were evaluated as indicators of BRONJ. Results: Necrosis and inflammation were not detected in group 1 (BP + relaxin). In group 3 (BP only), incidence rates of necrosis and inflammation were 90% and 60%, respectively. Conclusions: Our findings suggest that relaxin may be potently effective in preventing BRONJ and have some benefit in the treatment of existing BRONJ (AU)

Objetivo: A osteonecrose da mandíbula relacionada ao bisfosfonato (BRONJ) é uma desafiadora complicação do uso crônico de bisfosfonato (BP). O hormônio relaxina é capaz de induzir o processo múltiplo de diferenciação da osteoclastogênese humana, exibe ações anti-fibróticas e anti-inflamatórias e promove vasodilatação, cicatrização de feridas e angiogênese. O presente estudo teve como objetivo avaliar os efeitos da relaxina na prevenção e tratamento do BRONJ. Material e Métodos: Trinta e seis ratos Sprague Dawley machos foram divididos aleatoriamente em quatro grupos. Os ratos do grupo 1 (n = 10) receberam relaxina e BP simultaneamente por 12 semanas. Os ratos do grupo 2 (n = 10) receberam injeções de BP por 12 semanas, seguidos de relaxina por mais 12 semanas. Os ratos do grupo 3 (n = 10) receberam apenas injeções de BP e os do grupo 4 (controle, n = 6) receberam apenas solução salina. Necrose e inflamação nas mandíbulas dos ratos foram avaliadas como indicadores de BRONJ. Resultados: Necrose e inflamação não foram detectadas no grupo 1 (BP + relaxina). No grupo 3 (somente BP), as taxas de incidência de necrose e inflamação foram de 90% e 60%, respectivamente. Conclusões: Nossos resultados sugerem que a relaxina pode ser potentemente eficaz na prevenção do BRONJ e ter algum benefício no tratamento do BRONJ existente.(AU)