Association Between VKORC1 Gene Polymorphisms and Osteopenia and Osteoporosis: A Systematic Review and Meta-Analysis

Background and Objectives: The vitamin K epoxide reductase complex subunit 1 (VKORC1) plays a central role in the vitamin K cycle, which is essential for γ-carboxylation of multiple bone-related proteins. Genetic variants in VKORC1 may influence bone mineral density (BMD) and osteoporosis risk. Materials and Methods: A systematic review and meta-analysis were conducted to evaluate the association between VKORC1 polymorphisms and osteopenia and osteoporosis. Relevant studies were identified through PubMed, Scopus, and Web of Science databases. Data on study characteristics, genotypes, BMD measurement, ethnicity, sex, and menopausal status were extracted. Results: Six studies comprising 7335 participants were included. All studies assessed BMD using dual-energy X-ray absorptiometry (DXA). The mean participant age ranged from 41.9 to 63.7 years. The VKORC1 variants most frequently studied, which were included in the meta-analysis, were rs9923231 and rs9934438. The overall effect of VKORC1 risk alleles on osteopenia/osteoporosis was significant with a p = 0.041 (fixed effects OR = 1.16, 95% CI = 1.01-1.35). Heterogeneity among studies was insignificant (I² = 0%, p = 0.893). Conclusions: A modest association was observed for the VKORC1 variants. The current body of evidence requires further studies to elucidate whether VKORC1 polymorphisms have a clinically meaningful role in bone health.