Publications of the Week: Vitamin D and fractures


Vitamin D supplementation and fractures in midlife and older adults

LeBoff MS, Chou SH, Ratliff KA, et al. Supplemental Vitamin D and Incident Fractures in Midlife and Older Adults. N Engl J Med. 2022 Jul 28;387(4):299-309. doi: 10.1056/NEJMoa2202106. PMID: 35939577.

Background: Vitamin D supplementation is widely used in middle-aged to elderly people to maintain overall bone health alongside putative anticancer and immunity-enhancing benefits, but it is uncertain if vitamin D supplements prevent fractures.

Methods: This study, an ancillary component of VITAL (Vitamin D and Omega-3 Trial), assessed whether vitamin D supplementation would lower patients’ risk of fractures. VITAL is a 2 × 2 factorial, randomized, placebo-controlled trial investigating if supplemental vitamin D3 (2000 IU/d), n-3 fatty acids (1 g/d), or both prevent cancer and cardiovascular disease in men aged ≥50 years and women aged ≥55 years. Participants were not identified on the basis of whether they had vitamin D deficiency, low bone mass, or osteoporosis. Incident fractures were documented using yearly questionnaires given to participants and were adjudicated by an independent, centralized medical-record review. The primary end points were total fractures, nonvertebral fractures, and hip fractures. Proportional hazards models were applied to estimate the treatment effect using intention-to-treat analyses.

Results: There were 25,871 participants (50.6% women), with a median follow-up of 5.3 years. A total of 769 fractures occurred in 12,927 participants in the vitamin D group and 782 fractures in 12,944 participants in the placebo group, a difference that was not statistically significant (hazard ratio [HR], 0.98; 95% CI, 0.89-1.08). There was also no significant difference for the outcomes of nonvertebral fractures (HR, 0.97; 95% CI, 0.87-1.07) and hip fractures (HR, 1.01; 95% CI, 0.70-1.47). No modification of the treatment effect was observed according to baseline characteristics, including age, sex, race or ethnic group, body-mass index (BMI), or serum 25-hydroxyvitamin D levels. There were no substantial between-group differences in terms of adverse events as assessed in the parent trial. Subgroup analyses showed a similar lack of effect on fracture risk based on sex, age, race or ethnic group, and BMI.

Conclusions: The authors concluded that vitamin D3 supplementation did not result in a significantly lower risk of fractures compared with placebo among generally healthy midlife and older adults whose participation in the study was not due to vitamin D deficiency, low bone mass, or osteoporosis.

McMaster editors’ commentary: In this and related studies (doi: 10.1210/clinem/dgaa311; doi: 10.1016/j.cct.2011.09.009), there were no patient subgroups, whether with vitamin D insufficiency (25-hydroxyvitamin D level <30 ng/mL) or deficiency (<20 ng/mL), that benefited from vitamin D supplementation, which thereby questions the current approach of widespread screening and vitamin D supplementation. There may be a role for vitamin D to reduce fracture risk in selected patients, such as those who have limited exposure to sunlight or those who have genetic variations in vitamin D absorption and metabolism or receptor function. Notwithstanding these points, this is a paradigm-shifting study, especially as regards the limited value of wide screening for vitamin D deficiency.

See also

We would love to hear from you

Comments, mistakes, suggestions?

We use cookies to ensure you get the best browsing experience on our website. Refer to our Cookies Information and Privacy Policy for more details.