PMID:
Clin Chem. 2020 Apr 7. Epub 2020 Apr 7. PMID: 32255480
Abstract Title:
25-Hydroxyvitamin D and Risk of Osteoporotic Fractures: Mendelian Randomization Analysis in 2 Large Population-Based Cohorts.
Abstract:
BACKGROUND: Whether low plasma 25-hydroxyvitamin D concentrations cause osteoporotic fractures is unclear. We tested the hypothesis that low plasma 25-hydroxyvitamin D concentrations are associated with increased risk of osteoporotic fractures using a Mendelian randomization analysis.METHODS: We genotyped 116 335 randomly chosen white Danish persons aged 20-100 years in 2 population-based cohort studies for plasma 25-hydroxyvitamin D decreasing genotypes in CYP2R1 (rs117913124 and rs12794714), DHCR7 (rs7944926 and rs11234027), GEMIN2 (rs2277458), and HAL (rs3819817); 35 833 had information on plasma 25-hydroxyvitamin D. We assessed risk of total, osteoporotic, and anatomically localized fractures from 1981 through 2017. Information on fractures and vital status was obtained from nationwide registries.RESULTS: During up to 36 years of follow-up, we observed 17 820 total fractures, 10 861 osteoporotic fractures, and 3472 fractures of hip or femur. Compared with individuals with 25-hydroxyvitamin D ≥ 50nmol/L, multivariable adjusted hazard ratios (95% CIs) for total fractures were 1.03 (0.97-1.09) for individuals with 25-49.9 nmol/L, 1.19 (1.10-1.28) for individuals with 12.5-24.9 nmol/L, and 1.39 (1.21-1.60) for individuals with 25-hydroxyvitamin D
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