Clinician Article

Supplemental Vitamin D and Incident Fractures in Midlife and Older Adults.

  • LeBoff MS
  • Chou SH
  • Ratliff KA
  • Cook NR
  • Khurana B
  • Kim E, et al.
N Engl J Med. 2022 Jul 28;387(4):299-309. doi: 10.1056/NEJMoa2202106. (Original)
PMID: 35939577
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  • Family Medicine (FM)/General Practice (GP)
    Relevance - 7/7
    Newsworthiness - 6/7
  • General Internal Medicine-Primary Care(US)
    Relevance - 7/7
    Newsworthiness - 6/7
  • Internal Medicine
    Relevance - 6/7
    Newsworthiness - 6/7
  • Public Health
    Relevance - 6/7
    Newsworthiness - 6/7
  • Endocrine
    Relevance - 6/7
    Newsworthiness - 5/7


BACKGROUND: Vitamin D supplements are widely recommended for bone health in the general population, but data on whether they prevent fractures have been inconsistent.

METHODS: In an ancillary study of the Vitamin D and Omega-3 Trial (VITAL), we tested whether supplemental vitamin D3 would result in a lower risk of fractures than placebo. VITAL was a two-by-two factorial, randomized, controlled trial that investigated whether supplemental vitamin D3 (2000 IU per day), n-3 fatty acids (1 g per day), or both would prevent cancer and cardiovascular disease in men 50 years of age or older and women 55 years of age or older in the United States. Participants were not recruited on the basis of vitamin D deficiency, low bone mass, or osteoporosis. Incident fractures were reported by participants on annual questionnaires and adjudicated by centralized medical-record review. The primary end points were incident total, nonvertebral, and hip fractures. Proportional-hazards models were used to estimate the treatment effect in intention-to-treat analyses.

RESULTS: Among 25,871 participants (50.6% women [13,085 of 25,871] and 20.2% Black [5106 of 25,304]), we confirmed 1991 incident fractures in 1551 participants over a median follow-up of 5.3 years. Supplemental vitamin D3, as compared with placebo, did not have a significant effect on total fractures (which occurred in 769 of 12,927 participants in the vitamin D group and in 782 of 12,944 participants in the placebo group; hazard ratio, 0.98; 95% confidence interval [CI], 0.89 to 1.08; P = 0.70), nonvertebral fractures (hazard ratio, 0.97; 95% CI, 0.87 to 1.07; P = 0.50), or hip fractures (hazard ratio, 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, body-mass index, or serum 25-hydroxyvitamin D levels. There were no substantial between-group differences in adverse events as assessed in the parent trial.

CONCLUSIONS: Vitamin D3 supplementation did not result in a significantly lower risk of fractures than placebo among generally healthy midlife and older adults who were not selected for vitamin D deficiency, low bone mass, or osteoporosis. (Funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases; VITAL ClinicalTrials.gov number, NCT01704859.).

Clinical Comments


These results are contrary to commonly held beliefs among primary care physicians and endocrinologists and help confirm the lack of necessity for supplemental vitamin D. Self-reporting of fractures may be a limitation of the study, but I don't think so.

General Internal Medicine-Primary Care(US)

It would be useful to highlight this article for primary care physicians (PCP) and frame it in the context of Vit D levels and supplementation in general. There is an epidemic among my PCP peers of Vit D testing, patients being told they have "low Vit D", and supplements prescribed - all without any evidence of benefit that I can tell. My PCP colleagues should defend or abandon this routine practice.

General Internal Medicine-Primary Care(US)

This study seems to refute any benefit of vitamin D supplementation on bone health. I wonder whether the study was too short (5 years) to show a benefit in patients with baseline vitamin D deficiency, or whether a study that is long enough addressing this question will ever be done.

Internal Medicine

A well-designed trial demonstrating the lack of utility of Vitamin D supplementation when used to prevent fractures in generally healthy people. Note that this trial didn't measure supplementation effects specifically in Vitamin D-deficient people (as ethical concerns wouldn't allow for a placebo group). Nothing in this trial would obviate physicians from checking Vitamin D levels across their patients, but it does give ammunition to providers to help patients avoid unnecessary pills.

Internal Medicine

Poor vitamin D. It is low in nearly every disease process, so it makes common sense that replacing it would make everything better. In this large and very well done study, we are now adding more to the evidence that replacement does not prevent either falls or fractures. Fortunately, there were no harms (except potentially to the vitamin industry).

Public Health

As someone who takes vitamin D3 for vitamin D deficiency, the article's results are relevant to me. However, the authors state that "the trial was not designed to test the effects of vitamin D supplementation in those who are vitamin D deficient." They cite other studies, however, that found no advantage of vitamin D supplementation in persons who are vitamin D deficient. I suppose we must wait for additional studies. Meanwhile, should I continue taking vitamin D3 2000 IU daily, or am I wasting my money?

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