Modulation of Orthodontic Tooth Movement by Statins: A Systematic Review of Animal Studies

Objective: This systematic review aims to evaluate the effects of statin administration on orthodontic tooth movement (OTM) and post-treatment relapse in animal models. Materials and Methods: Following PRISMA guidelines and PROSPERO registration (CRD42025612449), a comprehensive literature search was performed in PubMed, Scopus, and the Cochrane Library up to December 2025. The search strategy included studies on animal models treated with any form of statin during OTM or relapse phases. Eligibility criteria were defined using the PICOS framework. Data extraction focused on study char- acteristics, statin administration protocol, orthodontic mechanics, and both histological and molecular markers of bone remodeling. Risk of bias was assessed with SYRCLE’s tool. Results: Seven in vivo animal studies met the inclusion criteria. Simvastatin and atorvastatin were investigated using heterogeneous experimental models, doses, admin- istration routes, orthodontic mechanics, and follow-up periods. Findings suggested that statins may reduce active orthodontic tooth movement or post-orthodontic relapse in some experimental settings, but effects were not uniform across studies. Histological outcomes, when reported, generally indicated reduced osteoclast activity, fewer resorption lacunae, or more mature alveolar bone in statin-treated animals. Molecular outcomes were less consistently reported and mainly involved OPG/RANKL-related pathways, Runx2, or ALP expression. Conclusions: Statins, particularly simvastatin, show potential to modulate orthodontic tooth movement and reduce relapse by influencing bone metabolism. Nev- ertheless, due to methodological variability and the exclusive reliance on animal models, these results cannot yet be translated into clinical recommendations. Current preclinical evidence suggests that statins may modulate bone remodeling during active orthodontic tooth movement and after appliance removal. However, the evidence remains limited to a small number of heterogeneous animal studies with incomplete reporting of key outcomes and several unclear risk-of-bias domains. Clinical translation is premature, and more standardized preclinical studies are required before human investigations can be justified.