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Abstract Background Alterations in bone metabolism may play a significant role in the early stages of femoral head necrosis, yet the causal relationship remains unclear. This study utilizes a two-sample Mendelian randomization (MR) approach to explore the genetic causal links between biochemical markers of bone metabolism, bone mineral density, and the risk of femoral head necrosis. Methods This study utilizes publicly available genome-wide association study (GWAS) datasets, with exposure factors including biochemical bone markers (25OHD, calcium, and alkaline phosphatase) and bone mineral density (measured at the lumbar spine, heel, femoral neck, and total body). The outcome of interest is osteonecrosis of the femoral head. We selected validated single nucleotide polymorphisms that are strongly associated with the exposure factors as instrumental variables. Mendelian randomization analysis was conducted using inverse variance weighting(IVW), MR-Egger regression, and weighted median estimation. Additionally, we performed analyses for horizontal pleiotropy, heterogeneity, and sensitivity. Results A total of 934 SNPs were included in this study. The MR analysis results indicate that the IVW analysis of 25OHD, Ca, and ALP did not reach statistical significance (25OHD OR = 1.006, 95%CI: 0.69–1.47, P = 0.975; Ca OR = 0.856, 95%CI: 0.43–1.70, P = 0.657; ALP OR = 1.022, 95%CI: 0.86–1.21, P = 0.801). However, bone density, including heel, lumbar spine, and total body bone density, showed a protective causal relationship with the onset of ONFH, while the results for femoral neck bone density did not reach statistical significance (lumbar spine BMD OR = 0.662, 95%CI: 0.48–0.91, P = 0.010; heel BMD OR = 0.726, 95%CI: 0.62–0.85, P |
