Examining the association between genetic polymorphisms and osteoporosis among post-menopausal women: a systematic review

Purpose: Postmenopausal osteoporosis (PMOP) is the most prevalent metabolic bone disease among women, characterized by significant bone density loss and increased fracture risk. With a genetic component, a systematic review was conducted on the association between genetic polymorphisms and PMOP risk. Methods: A comprehensive review of PubMed literature examined genetic polymorphisms linked to PMOP risk. The primary outcome was to identify the most frequently studied genes linked to PMOP. The secondary outcome was to perform a meta-analysis on the top genetic markers to assess their overall association with PMOP risk. Results: Six genes, accounting for 55.08 % of all studies, were strongly associated with PMOP. Of these, the VDR gene was featured in 35 articles (18.72 % of studies), TNFRSF11B in 23 (12.30 %), ESR1 in 18 (9.63 %), COL1A1 in 12 (6.42 %), MTHFR in 8 (4.27 %), and TGFb1 in 7 (3.74 %). Meta-analysis showed five markers significantly associated with PMOP: SNP rs1544410 (OR_G: 0.74 (0.59, 0.92)), SNP rs11568820 (OR_G: 1.40 (1.03, 1.91)), and SNP rs2228570 (OR_T: 1.39 (1.12, 1.73)) in the VDR gene; and PvuII variant (OR_P: 0.80 (0.67, 0.96)) in the ESR1 gene. Conclusion: This review strengthens the importance of conducting a robust, multi-ethnic, large cohort study with functional analysis to corroborate the findings of the six key genes associated with PMOP. Replicating these findings in larger and more diverse datasets is crucial to validate their biological relevance and potential clinical application.