Vitamin D supplementation flops for fracture prevention

Intake of supplemental vitamin D₃ falls short of reducing the incidence of fractures among generally healthy midlife and older adults as compared with placebo, according to data from the Vitamin D and Omega-3 Trial (VITAL).

VITAL was a two-by-two factorial, randomized, controlled trial that examined whether supplemental vitamin D₃ (2,000 IU/day), n−3 fatty acids (1 g/day), or both would prevent cancer and cardiovascular disease in men aged ≥50 years and women aged ≥55 years in the United States.

The present analysis included 25,871 participants (50.6 percent female, 20.2 percent Black). Recruitment was not based on vitamin D deficiency, low bone mass, or osteoporosis. All participants completed annual questionnaires detailing incident fractures.

Over a median follow-up of 5.3 years, a total of 1,991 incident fractures in 1,551 participants were recorded. Total fractures occurred in 769 of 12,927 participants in the vitamin D group and in 782 of 12,944 participants in the placebo group.

Multivariable Cox proportional hazards models confirmed that supplemental vitamin D₃ had no significant effect on the risk of total fractures as compared with placebo (hazard ratio [HR], 0.98, 95 percent confidence interval [CI], 0.89–1.08; p=0.70). The same was true for nonvertebral fractures (HR, 0.97, 95 percent CI, 0.87–1.07; p=0.50) and hip fractures (HR, 1.01, 95 percent CI, 0.70–1.47; p=0.96).

There was no modification of the treatment effect detected, with results being consistent in subgroups defined by baseline characteristics, including age, sex, race or ethnic group, body-mass index, or serum 25-hydroxyvitamin D levels.

In terms of safety, the incidence of adverse events was similar in the two groups, as was the case in the parent trial.