Local statins in periodontal therapy: solid evidence for Step 2, limited for surgery

Statins have long been recognized for their pleiotropic effects beyond lipid lowering — including anti-inflammatory, angiogenic, and osteogenic properties. The clinical question driving this systematic review and meta-analysis is whether locally delivered statins, when used as adjuncts to conventional periodontal therapy or pre-implant bone regeneration procedures, produce measurable improvements in clinical and radiographic outcomes compared to standard treatment alone.

The authors searched PubMed and Scopus through July 2025, following PRISMA 2020 guidelines and registering the protocol in PROSPERO. Inclusion was restricted to randomized controlled trials (RCTs) evaluating three statins — atorvastatin (ATV), rosuvastatin (RSV), and simvastatin (SIM) — delivered locally as adjuncts to Step 2 non-surgical periodontal therapy, Step 3 surgical periodontal therapy, or pre-implant regenerative procedures. Primary outcomes included probing pocket depth (PPD), clinical attachment level (CAL), bleeding on probing (BoP), and radiographic bone fill. Risk of bias was assessed using the Cochrane RoB 2 tool, and random-effects meta-analyses were conducted at standardized follow-up intervals — 6 months for Step 2 and 9 months for Step 3.

Twenty-one RCTs met inclusion criteria: 13 evaluating Step 2 therapy, 6 Step 3 therapy, and 2 pre-implant bone regeneration. In Step 2, adjunctive statins demonstrated clinically meaningful gains over scaling and root planing alone, with pooled mean differences of approximately 1.4–2.3 mm for PPD reduction and 1.7–2.2 mm for CAL gain. Simvastatin showed numerically larger pooled effects, though no head-to-head comparisons between molecules were available and heterogeneity across trials was high. In Step 3, three trials contributed to 9-month pooling and showed smaller but statistically significant benefits: PPD reduction of 0.80 mm and CAL gain of 0.69 mm, with moderate heterogeneity. The two pre-implant regeneration trials were too clinically heterogeneous in design, materials, and outcome reporting to allow quantitative synthesis, and their radiographic results were inconsistent.

For the practicing periodontist or implantologist, the take-home message is nuanced. The evidence for adjunctive local statins in non-surgical periodontal therapy is promising and consistent in direction, with effect sizes that are clinically relevant — particularly in deep residual pockets. In surgical periodontal contexts, the benefit exists but is more modest, and integration into regenerative protocols appears to be the setting where additional gains are most plausible. The pre-implant regeneration field remains too immature and fragmented to draw conclusions. High inter-study heterogeneity — in statin type, vehicle, concentration, and delivery method — limits direct comparisons and generalizability. Until multicenter RCTs with standardized protocols and outcome measures are conducted, locally delivered statins should be considered a biologically rational adjunct with emerging clinical support, rather than an established standard of care.