Circulating serum 25-hydroxyvitamin D levels and bone mineral density and osteoporotic vertebral fractures: A Mendelian randomization study.

BACKGROUND AND OBJECTIVES: Low serum 25-hydroxyvitamin D (25OHD) has been associated with osteoporosis and osteoporotic fracture, but whether these associations are causal remains unclear. METHODS: We identified 15 single-nucleotide polymorphisms (SNPs) affecting serum 25OHD levels in seven genes in the peripheral blood genomic deoxyribonucleic acid (DNA) of 2061 community-based people aged 20-92 years (711 men and 1350 women) and 200 outpatients aged 55-85 years with vertebral fractures (36 men and 164 women). Our study employs Mendelian randomization (MR) to determine the causal relationship between serum 25OHD concentration and bone mineral density (BMD), bone turnover markers (BTMs), and vertebral fracture. RESULTS: MR analysis indicated no correlation between hereditary 25OHD levels and BMD, procollagen type 1 N-terminal propeptide (P1NP), carboxy-terminal telopeptide of type 1 collagen (CTX), and vertebral fractures (all P > 0.05) in all participants. In participants aged 55-92 years, MR analysis revealed that low serum 25OHD levels (odds ratio [OR] = 1.38; 95% confidence interval [CI]: 1.07-1.79; P = 0.014) are causally associated with increased P1NP levels. In sensitivity analysis, MR-Egger regression and the Weighted-median estimator indicated no significant pleiotropy. CONCLUSIONS: Our findings suggest that baseline 25OHD levels are unlikely to have a large effect on risk of vertebral fractures. Larger MR studies and randomized controlled trials are required to investigate small effects.