Vitamin D Supplementation Does Not Influence Fracture Risk in the General Population

Hand holding a vitamin d supplement pill up to the sky, with bright sun

Clinicians frequently recommend vitamin D supplementation in the general population to promote bone health. In 2011, the Institute of Medicine concluded there is an increased risk of fractures at both low and high levels of 25-hydroxyvitamin D and called for more data from large randomized, controlled trials.

In 2021, the U.S. Preventive Services Task Force found no effect of supplemental vitamin D on fracture risk among community-dwelling adults with low vitamin D levels.

To address the conflicting evidence, Meryl S. LeBoff, MD, chief of the Calcium and Bone Section of the Division of Endocrinology, Diabetes and Hypertension at Brigham and Women’s Hospital, JoAnn E. Manson, MD, DrPH, chief of the Division of Preventive Medicine, and colleagues conducted an ancillary analysis of the Vitamin D and Omega-3 Trial (VITAL). In multiple analyses reported in The New England Journal of Medicine, they found vitamin D did not affect fracture risk in the general population.


VITAL, published in the NEJM in 2019, was a randomized, controlled, 2×2 factorial trial that investigated the effects of supplemental cholecalciferol (2,000 IU/day), omega-3 fatty acid (1 g/day), both or neither on primary prevention of cancer and cardiovascular disease. The participants were men aged ≥50 and women aged ≥55 from the general U.S. population, and all 50 states were represented.

The ancillary study included 25,871 individuals, mean age 67, 51% female, and 20% Black. Participants were not preselected for very low vitamin D levels, low bone mass or osteoporosis. At study entry, 10% had a history of fragility fracture and 4.8% were taking osteoporosis medications.

The 43% of participants using low-dose vitamin D supplements at baseline were allowed to continue (limited to 800 IU/day), as were the 21% taking calcium supplements (limited to 1,200 mg/day).

Primary Endpoints

The median follow-up was 5.3 years. After adjustment for age, sex, race/ethnicity, and the omega-3 fatty acid randomization group, supplemental vitamin D3 did not have a significant effect on new-onset fractures compared with placebo:

  • Total fractures—HR, 0.98 (P=0.70)
  • Nonvertebral fractures—HR, 0.97 (P=0.50)
  • Hip fractures—HR, 1.01 (P=0.96)

The effect was not modified by baseline age, sex, race/ethnicity, body mass index, or use of non-trial vitamin D/calcium or quartile of baseline 25-hydroxyvitamin D levels.

The statistical power was low among participants with osteoporosis and those on osteoporosis medications, and power was very limited among the small percent of participants with very low vitamin D levels.

Secondary Endpoints

The results for the secondary endpoints were the same as for the primary endpoints except that toe, finger, skull, periprosthetic and pathologic fractures were excluded. In these analyses, too, vitamin D had no significant effect on fracture risk compared with placebo.

In summary, in this very large randomized controlled study, high dose daily supplemental vitamin D vs placebo did not reduce incident fractures among generally healthy midlife and older adults. These results are not generalizable to adults with severe vitamin D deficiency or osteoporosis, adults on osteoporosis medications, or older adults living in residential communities.

Adverse Events

The incidence of hypercalcemia and kidney stones did not differ substantially between the vitamin D and placebo groups.

As another point of interest, the original analysis of VITAL showed no statistically significant association between vitamin D supplementation and the incidence of invasive cancer or cardiovascular events. However, vitamin D did reduce advanced cancer (metastatic and/or fatal cases).

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