Circulating Serum 25-Hydroxyvitamin D Levels and Bone Mineral Density: Mendelian Randomization Study.
J Bone Miner Res. 2018 Jan 16;: Authors: Larsson SC, Melhus H, Michaëlsson K
There is considerable discussion of the importance for increased serum 25-hydroxyvitamin D (S-25OHD) concentration associated with adequacy for bone health. Accordingly, whether long-term high S-25OHD concentration in general positively affects bone mineral density (BMD) is uncertain. We used a Mendelian randomization design to determine the association between genetically increased S-25OHD concentrations and BMD. Five single-nucleotide polymorphisms (SNPs) in or near genes encoding enzymes and carrier proteins involved in vitamin D synthesis or metabolism were used as instrumental variables to genetically predict one standard deviation increase in S-25OHD concentration. Summary statistics data for the associations of the S-25OHD-associated SNPs with DXA-derived femoral neck and lumbar spine BMD were obtained from the GEnetic Factors for OSteoporosis Consortium (32,965 individuals) and ultrasound-derived heel estimated BMD from the UK Biobank (142,487 individuals). None of the SNPs was associated with BMD at Bonferroni-corrected significance level but there was a suggestive association between rs6013897 near CYP24A1 and femoral neck BMD (p = 0.01). In Mendelian randomization analysis, genetically predicted one standard deviation increment of S-25OHD was not associated with higher femoral neck BMD (standard deviation change in BMD 0.02; 95% CI, -0.03 to 0.07; p = 0.37), lumbar spine BMD (standard deviation change in BMD 0.02; 95% CI, -0.04 to 0.08; p = 0.49), or estimated BMD (g/cm2 change in BMD -0.03; 95% CI, -0.05 to -0.01; p = 0.02). This study does not support a causal association between long-term elevated S-25OHD concentrations and higher BMD in in generally healthy populations. These results suggest that more emphasis should be placed on the development of evidence-based cutoff points for vitamin D inadequacy rather than a general recommendation to increase S-25OHD. This article is protected by copyright. All rights reserved. PMID: 29338102 [PubMed - as supplied by publisher]