The Effect of Statin Therapy on Bone Metabolism Markers and Mineral Density: Aa GRADE-Assessed Systematic Review and Dose-Response Meta-Analysis of Randomized Controlled Trials.

Purpose: Statin therapy is widely used for the management of dyslipidemia and the prevention of cardiovascular diseases (CVDs). However, there is a growing concern about its potential effects on bone metabolism markers and mineral density. The aim of this systematic review and meta-analysis was to investigate the effect of statin therapy on these parameters.

Methods: PubMed/MEDLINE, Scopus, and Clarivate Analytics Web of Science databases were searched from inception to August 2023, using MESH terms and keywords.

Results: After screening 2450 articles, 16 studies that met the inclusion criteria were included, of which 12 randomized controlled trials (RCTs) were used for meta-analysis. The findings showed that statin therapy significantly reduced bone-specific alkaline phosphatase (B-ALP) levels (WMD=-1.1 U/L; 95% CI -2.2 to -0.07; P=0.03; I²=0%,), and bone mineral density (BMD) at different sites (WMD=-0.06 g/cm²; 95% CI -0.08 to -0.04; P<0.001; I²=97.7%, P<0.001). However, this treatment did not have a significant effect on osteocalcin, serum C-terminal peptide of type I collagen (S-CTx), serum N-telopeptides of type I collagen (NTx) concentration, or overall fracture risk.

Conclusion: This systematic review and meta-analysis provide evidence that statin therapy is associated with a significant reduction in B-ALP levels and BMD at different sites of the skeleton. Further studies are needed to investigate the long-term effects of statin therapy on bone health and to identify the potential underlying mechanisms.