Yunus Çolak 1,2,3 , Shoaib Afzal 1,2,3 , Børge G Nordestgaard 1,2,3,4 Show Affiliations »
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 < 12.5 nmol/L. Corresponding hazard ratios were 1.07 (1.00-1.15), 1.25 (1.13-1.37), and 1.49 (1.25-1.77) for osteoporotic fractures and 1.09 (0.98-1.22), 1.37 (1.18-1.57), and 1.41 (1.09-1.81) for fractures of hip or femur, respectively. Hazard ratios per 1 increase in vitamin D allele score, corresponding to 3.0% (approximately 1.6 nmol/L) lower 25-hydroxyvitamin D concentrations, were 0.99 (0.98-1.00) for total fractures, 0.99 (0.97-1.00) for osteoporotic fractures, and 0.98 (0.95-1.00) for fractures of hip or femur. CONCLUSIONS: Low plasma 25-hydroxyvitamin D concentrations were associated with osteoporotic fractures; however, Mendelian randomization analysis provided no evidence supporting a causal role for vitamin D in the risk for osteoporotic fractures. © American Association for Clinical Chemistry 2020. All rights reserved. For permissions, please email: journals.permissions@oup.com.
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 < 12.5 nmol/L. Corresponding hazard ratios were 1.07 (1.00-1.15), 1.25 (1.13-1.37), and 1.49 (1.25-1.77) for osteoporotic fractures and 1.09 (0.98-1.22), 1.37 (1.18-1.57), and 1.41 (1.09-1.81) for fractures of hip or femur, respectively. Hazard ratios per 1 increase in vitamin D allele score, corresponding to 3.0% (approximately 1.6 nmol/L) lower 25-hydroxyvitamin D concentrations, were 0.99 (0.98-1.00) for total fractures , 0.99 (0.97-1.00) for osteoporotic fractures , and 0.98 (0.95-1.00) for fractures of hip or femur. CONCLUSIONS: Low plasma 25-hydroxyvitamin D concentrations were associated with osteoporotic fractures ; however, Mendelian randomization analysis provided no evidence supporting a causal role for vitamin D in the risk for osteoporotic fractures . © American Association for Clinical Chemistry 2020. All rights reserved. For permissions, please email: journals.permissions@oup.com.
Entities: Chemical
Disease
Gene
Mutation
Species
Keywords:
Bone; Calcium; Dietary Supplements; Endocrine System; Epidemiology; Fractures; Genetic Polymorphism; Metabolism; Osteoporosis; Vitamin D
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Substances： See more »
Year: 2020
PMID： 32255480 DOI： 10.1093/clinchem/hvaa049
Source DB: PubMed Journal: Clin Chem ISSN： 0009-9147 Impact factor: 8.327