Calcium Plus Vitamin D for Fracture Prevention


Am Fam Physician. 2006 Jun 1;73(11):2030-2033.

Clinical Question: Does supplementation with 1,000 mg of calcium and 400 IU of vitamin D reduce the risk of fracture in healthy women?

Setting: Population-based

Study Design: Randomized controlled trial (double-blinded)

Allocation: Uncertain

Synopsis: A previous meta-analysis limited to studies in which women received more than 400 IU of vitamin D found a significant (37 percent) reduction in vertebral fractures (Papadimitropoulos E, et al., for the Osteoporosis Methodology Group and the Osteoporosis Research Advisory Group. Meta-analysis of therapies for postmenopausal osteoporosis. VIII: Meta-analysis of the efficacy of vitamin D treatments in preventing osteoporosis in postmenopausal women. Endocr Rev 2002;23:560–9). In this substudy of the Women's Health Initiative, 36,282 community-dwelling women were randomized to receive 1,000 mg calcium and 400 IU vitamin D per day or placebo. The study had 85 percent power to detect an 18 percent decrease in hip fractures and 99 percent power to detect an 18 percent decrease in total fractures.

The primary outcome was the number of hip fractures, and a secondary outcome was total fractures. Fractures of the ribs, sternum, skull, face, fingers, toes, and cervical vertebrae did not contribute to the total fracture number. The groups were balanced at the start of the study, analysis was by intention to treat, and the number of patients who dropped out or were lost to follow-up was modest (approximately 500 in each group). After a mean of seven years, there was a nonsignificant trend toward fewer hip fractures (0.14 versus 0.16 percent per year; hazard ratio [HR] = 0.88; 95% confidence interval [CI], 0.72 to 1.08) and a similar non-significant trend toward fewer total fractures (1.64 versus 1.70 percent). The authors did a post hoc subgroup analysis and found that if there was any benefit, it was among older women and women who fell less often.

Women who were adherent to the calcium and vitamin D regimen also had fewer hip fractures (relative risk = 0.71; 95% CI, 0.52 to 0.97). The total intake of calcium and vitamin D from diet and supplements varied considerably, with no clear trend toward greater benefit in women ingesting more of either substance. All-cause mortality was lower in the supplement group, although this did not reach statistical significance (HR = 0.91; 95% CI, 0.83 to 1.01). Women in the supplement group had 17 percent more kidney stones. A subgroup also had regular bone mineral density measurements, which showed greater preservation of bone density among women taking the supplements.

Bottom Line: The ability of a small dose of calcium and vitamin D to prevent fractures in healthy community-dwelling women is modest at best. This study used a relatively low dose of vitamin D (less than the 700 to 800 IU found most beneficial in previous studies), and the patients were generally at low risk of fracture. Perhaps that explains the discordance of these findings with the bulk of the literature on this topic. (Level of Evidence: 1b)

Study Reference

Jackson RD, et al., for the Women's Health Initiative Investigators. Calcium plus vitamin D supplementation and the risk of fractures [Published correction appears in N Engl J Med 2006;354:1102]. N Engl J Med. February 16, 2006;354:669–83.

Used with permission from Ebell M. 1000 mg calcium/400 IU vit D not very effective for fracture prevention (WHI). Accessed March 29, 2006, at:http://www.InfoPOEMs.com.



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May 15, 2019

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