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

<i>Background and Objectives:</i> 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 <i>VKORC1</i> may influence bone mineral density (BMD) and osteoporosis risk. <i>Materials and Methods:</i> A systematic review and meta-analysis were conducted to evaluate the association between <i>VKORC1</i> 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. <i>Results</i>: 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 <i>VKORC1</i> variants most frequently studied, which were included in the meta-analysis, were rs9923231 and rs9934438. The overall effect of <i>VKORC1</i> risk alleles on osteopenia/osteoporosis was significant with a <i>p</i> = 0.041 (fixed effects OR = 1.16, 95% CI = 1.01-1.35). Heterogeneity among studies was insignificant <i>(I</i>² = 0%, <i>p</i> = 0.893). <i>Conclusions:</i> A modest association was observed for the <i>VKORC1</i> variants. The current body of evidence requires further studies to elucidate whether <i>VKORC1</i> polymorphisms have a clinically meaningful role in bone health.