Effect of Bisphosphonates on Orthodontic Relapse Prevention: A Systematic Review of Animal Studies Publisher



Shafiei H ; Tahmasbi S ; Farahani A ; Bastami F
Source: Iranian Journal of Orthodontics Published:2026

Abstract

Aim Orthodontic relapse (OR) frequently compromises post-treatment stability. Bisphosphonates (BPs), as potent inhibitors of bone resorption, have been proposed as potential agents to reduce relapse. This systematic review evaluated the effects of BP administration on OR prevention in animal models. Methods Prospective controlled animal studies investigating systemic or local BP administration immediately after orthodontic tooth movement or stabilization were included. Human or in vitro studies or studies not involving OTM were excluded. PubMed, Cochrane, Web of Science, EMBASE, and Scopus were searched to October 13, 2025. Two reviewers independently screened studies, extracted data, and assessed risk of bias using the SYRCLE tool. Evidence certainty was evaluated using GRADE. Owing to marked methodological heterogeneity, data were synthesized qualitatively. Results Seven studies (rats n=4, guinea pigs n=2, goats n=1) involving various BPs (risedronate, pamidronate, alendronate, 4-amino-1-hydroxybutylidene-1,1-bisphosphonate) and systemic or localized routes were included. All studies reported reduced OR in BPs-treated groups compared with controls. Quantitative outcomes included decreased relapse distance/percentage and reduced osteoclast counts. However, substantial heterogeneity in animal models, dosing regimens, administration routes, and relapse measurement protocols, combined with consistently high or unclear risk of bias, limited data comparability. The overall certainty of evidence was rated very low (GRADE) due to serious RoB, inconsistency, indirectness, and imprecision. Conclusion Preclinical evidence suggests that BPs may reduce orthodontic relapse, particularly with localized delivery; however, confidence in these findings is very low. Current animal data are insufficient to support clinical application. High-quality, standardized, long-term animal studies are needed before translation to human research. © 2026, Author(s).