Local simvastatin as an adjunct to dental implant therapy: a systematic review and exploratory meta-analysis of peri-implant bone outcomes

Local simvastatin has been investigated as an adjunct to dental implant placement because of its osteogenic, angiogenic, and anti-inflammatory potential, but clinical effectiveness remains uncertain. To evaluate the effects and safety of locally administered simvastatin on peri-implant bone outcomes, implant stability, implant survival, and adverse events. Comparative clinical studies were identified through PubMed/MEDLINE, Embase, Scopus, Web of Science Core Collection, and LILACS, supplemented by reference checking and a targeted ClinicalTrials.gov update. Study selection, data extraction, and risk-of-bias assessment were performed independently by two reviewers. Randomized trials were assessed with RoB 2 and non-randomized studies with ROBINS-I. Quantitative synthesis was restricted a priori at the analysis stage to clinically comparable treatment contrasts, outcome definitions, and follow-up periods. Random-effects inverse-variance models used a conservative modified Hartung-Knapp approach. Certainty was evaluated with GRADE. Eight published comparative studies involving 236 participants were included after reassessment of eligibility. The studies differed substantially in implant timing, anatomical site, simvastatin formulation and carrier, cointerventions, comparators, and outcome measurement. Consequently, the previous heterogeneous 12-month pooling was withdrawn. The only retained exploratory meta-analysis included two clinically comparable studies of PRF plus simvastatin versus PRF alone for early marginal bone loss and favored the simvastatin combination (mean difference, -0.21 mm; 95% CI, -0.39 to -0.03; p = 0.043; I²=0%), although the estimate was based on only two small studies and remained very-low-certainty evidence. Sensitivity analyses for plausible within-participant correlations in the split-mouth study did not materially alter the direction of effect. No consistent improvement was demonstrated for implant stability, survival, or patient-reported outcomes, and adverse-event reporting was sparse. Local simvastatin may reduce early peri-implant marginal bone loss in a narrowly defined PRF-based protocol, but the finding is hypothesis-generating. Heterogeneous clinical protocols should not be interpreted as supporting a common treatment effect, and current evidence is insufficient to justify routine clinical use. PROSPERO CRD420261440820.