OBJECTIVE: Orthodontic appliances are commonly used to achieve anchorage during orthodontic treatments
however, their use can contribute to oral diseases. Studies have shown that bisphosphonates and osteoprotegerin are highly effective in reducing orthodontic tooth movement. To determine the efficacy of bisphosphonates and osteoprotegerin in reducing orthodontic tooth movement. METHODS: A comprehensive search was conducted across five databases-MEDLINE-PubMed, Scopus, Google Scholar, ScienceDirect, and Taylor & Francis-up to August 2, 2023. Clinical trials conducted in healthy animals, where bisphosphonates and osteoprotegerin were administered during tooth movement, were included. The search identified 3,099 articles, which underwent a two-phase screening process, resulting in twelve studies for the systematic review and seven for the meta-analysis. Risk of bias was assessed using the SYRCLE tool, and Egger's regression was used to evaluate publication bias. RESULTS: The administration of bisphosphonates was more effective than osteoprotegerin in reducing mesiodistal orthodontic movement. However, osteoprotegerin did not significantly reduce orthodontic tooth movement. CONCLUSIONS: The findings align with previous studies, confirming the superior efficacy of bisphosphonates over osteoprotegerin. Further research is required to determine the optimal dosage and mechanism of action for these drugs in clinical practice, considering the specific objectives of orthodontic treatments.