Tabriz University of Medical Sciences Advanced Pharmaceutical Bulletin 2228-5881 14 3 2024 10 10 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 591 603 10.34172/apb.2024.051 EN Seyyed Mostafa Arabi https://orcid.org/0000-0002-0586-6503 Mahla Chambari Leila Sadat Bahrami Ali Jafari Hossein Bahari Željko Reiner Amirhossein Sahebkar https://orcid.org/0000-0002-8656-1444 Journal Article 10.34172/apb.2024.051 2023 11 04 2024 06 19 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.