Simvastatin as a Biological Adjunct to Guided Bone Regeneration and Related Implant Regenerative Procedures: A Systematic Review

Tooth extraction is followed by progressive alveolar ridge resorption, which can compromise implant positioning, peri-implant hard tissue support, and esthetic outcomes. Guided bone regeneration (GBR) and related implant-site regenerative approaches are therefore frequently used to improve peri-implant healing. Simvastatin, a 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor, has shown osteopromotive, anti-inflammatory, and angiogenic effects and has recently been explored as a local adjunct in implant-associated regenerative procedures. This systematic review evaluated the available human and animal evidence on localized simvastatin used with GBR or related regenerative protocols during implant placement. This systematic review was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines and registered in PROSPERO (CRD420251037455). Electronic searches of PubMed/MEDLINE, Embase, Scopus, Web of Science, Cochrane CENTRAL, Google Scholar, and ClinicalTrials.gov were performed from database inception to April 30, 2025. Randomized controlled trials (RCTs), controlled clinical studies, and animal studies evaluating local simvastatin in implant-associated regenerative procedures were eligible. Data were synthesized qualitatively because of heterogeneity in study design, simvastatin delivery systems, comparator protocols, and outcome measures. Five studies were included: three human clinical studies and two animal studies. In the human studies, simvastatin was associated with reduced peri-implant bone loss (0.975±0.0438 mm versus 1.356±0.0384 mm; P<0.0001), improved probing depth and bleeding scores, greater bone width gain (5.55±0.80 mm versus 3.36±0.19 mm), and higher bone mineral density (640.02±262.22 versus 297.38±82.94) compared with controls. In the animal studies, simvastatin improved bone-to-implant contact and bone area; for example, grafted bone-to-implant contact at four weeks increased from 59.5% in controls to 84.3% in simvastatin-treated sites, while grafted bone area increased from 51.4% to 75.9%. Implant stability findings were mixed, and no major adverse effects were reported. The available evidence suggests that locally delivered simvastatin may improve hard tissue regeneration and selected peri-implant clinical outcomes when used with GBR or related implant regenerative protocols. However, the evidence base is limited by the small number of studies, mixed human and animal designs, and heterogeneity in simvastatin concentration, carrier systems, and follow-up periods. Larger, well-designed clinical trials with standardized protocols are needed before routine clinical use can be recommended.