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Adjunctive Use of Locally Delivered Statins in Periodontal Therapy and Pre-Implant Bone Regeneration: A Systematic
Koki Yoshida1, Sofia Heller2, Nur Mousa2
1Division of Oral Medicine and Pathology, Department of Human Biology and Pathophysiology, School of Dentistry, Health Sciences University of Hokkaido, Hokkaido, Japan.
Objectives:
This systematic review and meta-analysis aimed to evaluate the adjunctive beneficial effects of locally delivered statins on probing pocket depth (PPD), clinical attachment level (CAL), bleeding on probing (BoP), and radiographic bone outcomes in both periodontal therapy (Step 2 non-surgical periodontal therapy and Step 3 periodontal surgery) and pre-implant bone regeneration procedures.
Methods:
The review followed the PRISMA 2020 statement and was registered in PROSPERO (CRD420251105739). PubMed and Scopus were searched through July 2025 for randomized controlled trials (RCTs) evaluating the adjunctive use of locally delivered atorvastatin (ATV), rosuvastatin (RSV), or simvastatin (SIM) in periodontal therapy and pre-implant regenerative procedures. Risk of bias was assessed using the Cochrane Risk of Bias 2 tool (RoB 2). Random-effects meta-analysis was conducted when extractable data were available at commonly reported follow-ups (6 months for Step 2; 9 months for Step 3).
Results:
Twenty-one RCTs were included (13 Step 2, 6 Step 3, 2 pre-implant bone regeneration). In Step 2 therapy, adjunctive statins improved clinical outcomes compared with scaling and root planing alone, with pooled mean differences (MDs) of approximately 1.4-2.3 mm for PPD and 1.7-2.2 mm for CAL. Numerically larger pooled effects were observed for SIM; however, no direct head-to-head comparisons between statins were performed, and heterogeneity was high. In Step 3 therapy, three trials contributed to 9-month pooling, showing smaller but significant benefits (PPD MD 0.80 mm; CAL MD 0.69 mm), with moderate heterogeneity. Pre-implant bone regeneration trials were clinically heterogeneous and showed inconsistent radiographic outcomes, precluding quantitative synthesis.
Conclusions:
Locally delivered statins provide clinically relevant adjunctive benefits in Step 2 periodontal therapy and modest additional improvements in Step 3 therapy, particularly when incorporated into regenerative protocols. Evidence for pre-implant bone regeneration remains limited and heterogeneous. Further multicenter RCTs with standardized clinical and radiographic outcomes are needed.
