Objective

Severe vitamin D deficiency causes osteomalacia, yet trials of vitamin D supplementation in the community have not consistently benefited BMD or fracture risk in adults. This study determined whether a higher dose of vitamin D influenced BMD and whether benefit was dependent on baseline 25-hydroxyvitamin D concentrations.

Methods

This is a sub-study of ViDA, an RCT which recruited community-resident adults aged 50-84 years. 452 entered the sub-study and 418 completed 2 years. Participants were randomized to receive oral vitamin D3 in an initial dose of 200,000 IU, followed by monthly doses of 100,000 IU, or placebo, for 2 years. The primary endpoint was change in lumbar spine BMD, with other BMD sites as secondary endpoints. Exploratory analyses to identify thresholds of baseline 25-hydroxyvitamin D for vitamin D effects on BMD were pre-specified.

Results

Intention-to-treat analyses showed no treatment effect in the spine or total body, but BMD loss at both hip sites was significantly attenuated over 2 years by ~½%. There was a significant interaction between baseline 25-hydroxyvitamin D and treatment effect (P=0.04). In participants with baseline 25-hydroxyvitamin D ≤30 nmol/L (n=46), there were between-groups differences in BMD changes at the spine and femoral sites of ~2%, significant in the spine and femoral neck. When baseline 25-hydroxyvitamin D levels were >30 nmol/L, between-groups BMD differences were ~½% and significant only at the total hip.

Conclusions

The primary analysis of this study does not demonstrate a clinically important benefit to BMD from untargeted vitamin D supplementation of older community-dwelling adults. Exploratory analyses suggest meaningful benefit in those with baseline 25-hydroxyvitamin D ≤30 nmol/L, suggesting that any future trials should focus on this group. These findings represent a significant step towards a trial-based definition of vitamin D deficiency for bone health in older adults.