Vitamin D not causally linked to bone mineral density

A recent Mendelian randomization study has found no causal link between vitamin D and bone mineral density (BMD).

Drawing from a large-scale European genome-wide association study, the researchers extracted 143 independent single-nucleotide polymorphisms (SNPs) to assess potential effects on the association between 25-hydroxyvitamin D (25OHD) levels and BMD. The median and mean 25OHD levels in the study cohort were 47.9 and 49.6 nmol/L, respectively, and showed the expected seasonal variation.

Overall, SNPs accounted for 5.4 percent of the phenotypic variation in serum 25OHD.

After further narrowing down the SNPs, 107 variations remained eligible for the two-sample Mendelian randomization analysis. Across all body sites and analytic methods, only ultrasound-measured heel BMD was causally linked with 25OHD, and only when using the robust adjusted profile score method (effect, –40.1677, 95 percent confidence interval, –69.3513 to –10.9841; p=0.007).

In contrast, total body BMD, as well as BMD at the forearm, femoral neck, and lumbar spine showed no such interaction with 25OHD. Similarly, using various Mendelian randomization methods—such as the weighted median, inverse variance weighted, and Egger regression—revealed no other causal interactions. Though heterogeneous, these findings remained robust in sensitivity analysis.

“Our two-sample Mendelian randomization analysis did not support the causal effect of 25OHD on BMD at different skeletal sites across the lifespan. Updated randomized controlled trials are warranted to investigate the role of vitamin D supplementation in the prevention of osteoporosis in the high-risk populations,” the researchers said.