Vitamin D supplementation did not result in a significantly lower risk of fractures than placebo among generally healthy midlife and older adults, a study found.
The Vitamin D and Omega-3 Trial (VITAL) was a two-by-two factorial randomized controlled trial that investigated whether supplemental vitamin D (2,000 IU/d), n−3 fatty acids (1 g/d), or both would prevent cancer and cardiovascular disease in men 50 years of age or older and women 55 years of age or older. Participants were not recruited based on vitamin D deficiency, low bone mass, or osteoporosis.
This ancillary study looked at the outcome of incident fractures, reported by participants on annual questionnaires or medical-record review. Primary end points were incident total, nonvertebral, and hip fractures. Secondary end points were incident total, nonvertebral, and hip fractures, with the exclusion of toe, finger, skull, periprosthetic, and pathologic fractures. The study was published by the New England Journal of Medicine on July 28.
Among 25,871 participants (50.6% women; 20.2% Black), there were 1,991 incident fractures in 1,551 participants over a median follow-up of 5.3 years. Supplemental vitamin D, as compared with placebo, did not have a significant effect on total fractures (hazard ratio [HR], 0.98; 95% CI, 0.89 to 1.08; P=0.70), nonvertebral fractures (HR, 0.97; 95% CI, 0.87 to 1.07; P=0.50), or hip fractures (HR, 1.01; 95% CI, 0.70 to 1.47; P=0.96).
There was no modification of the treatment effect according to baseline characteristics, including age, sex, race or ethnic group, or body mass index. Baseline 25-hydroxyvitamin D levels, when stratified above or below the median (31 ng/mL) or in quartiles (≤24.0, 24.1 to 30.0, 30.1 to 36.9, or ≥37.0 ng/mL), did not modify the effects of supplemental vitamin D as compared with placebo on incident total, nonvertebral, or hip fractures. In sensitivity analyses, results did not change by whether participants were adherent to trial pills, and no latency effect was found. Supplemental vitamin D also did not result in a lower risk of recurrent fractures than placebo.
Findings for vitamin D versus placebo were similar for exploratory end points, including major osteoporotic fractures (HR, 0.99; 95% CI, 0.83 to 1.17), pelvic fractures (HR, 1.08; 95% CI, 0.64 to 1.80), and wrist fractures (HR, 0.89; 95% CI, 0.69 to 1.15).
“In VITAL, we previously found that vitamin D supplementation did not affect incident fall risk or changes in bone mineral density or structure,” the study authors wrote. “Ongoing studies in VITAL are assessing whether baseline measured free 25-hydroxyvitamin D levels or genetic variation in vitamin D absorption, metabolism, or receptor function may identify a subgroup of patients who may benefit from vitamin D supplementation with respect to fracture outcomes.”