Is Vitamin D supplementation useless to prevent fractures in the general population?

While there is currently insufficient evidence to prove that Vitamin D supplementation might prevent cancer or cardiovascular events, several meta-analyses have shown a benefit of Vitamin D plus calcium to prevent hip fractures. This was also seen in a per-protocol analysis of a Women’s Health Initiative study.

The Vitamin D and Ometa-3 Trial or VITAL was a randomized placebo-controlled trial of cholecalciferol (that’s Vitamin D3) and omega-3 fatty acids. Since they tested two interventions, this was studied in two-by-two factorial design. Vitamin D was given as 2000 units daily and the daily omega-3 pills contained 1g of fatty acids. This was an ancillary study of a trial that is hypothesized to test whether these interventions, alone or together, can prevent cancer and cardiovascular disease. The study population is men over 50 and women over 55. There were no other in- or exclusion criteria except that patients could not already have cancer or cardiovascular disease, and also they couldn’t have hypercalcemia.

The study population had a mean age of 67, 51% were female. They recruited entirely in the U.S. and they had 71% Caucasians and 20% African Americans. Notably, it was allowed that patients were already taking Vitamin D supplements, and 43% already did so. 5% were taking osteoporosis medications and 10% had a previous frigitilty fracture. The baseline mean vitamin D level was over 30 ng/ml.

Over the course of the median 5.3 years of follow-up, Vitamin D did not prevent fractures in the total fracture group. The same was true for non-vertebral and hip fractures subgroups.

Our guest, WuQiang Fan, M.D., Ph.D., is an endocrinologist and hospitalist at Mass General Hospital and an Instructior in Medicine at Harvard Medical School. He often functions in the role of the Fracture Liaison Services, seeing patients with a new fracture in consultation, where he might be asked to assess what preventative therapies patients might quality for.

References:

-MS LeBoff et al.. N Engl J Med . 2022 Jul 28;387(4):299-309. https://pubmed.ncbi.nlm.nih.gov/35939577/

-USPSTF: Final Recommendation Statement. Vitamin D, Calcium, or Combined Supplementation for the Primary Prevention of Fractures in Community-Dwelling Adults https://www.uspreventiveservicestaskforce.org/uspstf/recommendation/vitamin-d-calcium-or-combined-supplementation-for-the-primary-prevention-of-fractures-in-adults-preventive-medication

-USPSTF: Final Recommendation Statement. Vitamin D Deficiency in Adults: Screening. https://www.uspreventiveservicestaskforce.org/uspstf/recommendation/vitamin-d-deficiency-screening (retrieved Nov 11, 2022)

-MF Holick, […], Endocrine Society. J Clin Endocrinol Metab. 2011 Jul;96(7):1911-30. https://pubmed.ncbi.nlm.nih.gov/21646368/

-NEJM Journal Watch Clincal Conversations. Podcast 297, July 29, 2022. https://pca.st/fhr0cdyo

-Three previous meta-analyses in osteoporotic women that included Vitamin D and calcium:

1) MJ Bolland et al.: Calcium intake and risk of fracture: systematic review . BMJ . 2015 Sep 29;351:h4580. https://pubmed.ncbi.nlm.nih.gov/26420387/

2) DIPART Group. BMJ. 2010;340:b5463. https://pubmed.ncbi.nlm.nih.gov/20068257/

3) A Avenell, JC Mak, and D O'Connell. Cochrane Database Syst Rev. 2014. https://pubmed.ncbi.nlm.nih.gov/24729336/

RD Jackson et al. N Engl J Med. 2006 Feb 16;354(7):669-83. https://pubmed.ncbi.nlm.nih.gov/16481635/

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