Calcium plus vitamin D supplementation and the risk of fractures

Rebecca D. Jackson, Andrea Z. LaCroix, Margery Gass, Robert B. Wallace, John Robbins, Cora E. Lewis, Tamsen Bassford, Shirley A.A. Beresford, Henry R. Black, Patricia Blanchette, Denise E. Bonds, Robert L. Brunner, Robert G. Brzyski, Bette Caan, Jane A. Cauley, Rowan T. Chlebowski, Steven R. Cummings, Iris Granek, Jennifer Hays, Gerardo HeissSusan L. Hendrix, Barbara V. Howard, Judith Hsia, F. Allan Hubbell, Karen C. Johnson, Howard Judd, Jane Morley Kotchen, Lewis H. Kuller, Robert D. Langer, Norman L. Lasser, Marian C. Limacher, Shari Ludlam, Joann E. Manson, Karen L. Margolis, Joan McGowan, Judith K. Ockene, Mary Jo O'Sullivan, Lawrence Phillips, Ross L. Prentice, Gloria E. Sarto, Marcia L. Stefanick, Linda Van Horn, Jean Wactawski-Wende, Evelyn Whitlock, Garnet L. Anderson, Annlouise R. Assaf, David Barad

Research output: Contribution to journalArticlepeer-review

1586 Scopus citations


BACKGROUND: The efficacy of calcium with vitamin D supplementation for preventing hip and other fractures in healthy postmenopausal women remains equivocal. METHODS: We recruited 36,282 postmenopausal women, 50 to 79 years of age, who were already enrolled in a Women's Health Initiative (WHI) clinical trial. We randomly assigned participants to receive 1000 mg of elemental calcium as calcium carbonate with 400 IU of vitamin D3 daily or placebo. Fractures were ascertained for an average follow-up period of 7.0 years. Bone density was measured at three WHI centers. RESULTS: Hip bone density was 1.06 percent higher in the calcium plus vitamin D group than in the placebo group (P<0.01). Intention-to-treat analysis indicated that participants receiving calcium plus vitamin D supplementation had a hazard ratio of 0.88 for hip fracture (95 percent confidence interval, 0.72 to 1.08), 0.90 for clinical spine fracture (0.74 to 1.10), and 0.96 for total fractures (0.91 to 1.02). The risk of renal calculi increased with calcium plus vitamin D (hazard ratio, 1.17; 95 percent confidence interval, 1.02 to 1.34). Censoring data from women when they ceased to adhere to the study medication reduced the hazard ratio for hip fracture to 0.71 (95 percent confidence interval, 0.52 to 0.97). Effects did not vary significantly according to prerandomization serum vitamin D levels. CONCLUSIONS: Among healthy postmenopausal women, calcium with vitamin D supplementation resulted in a small but significant improvement in hip bone density, did not significantly reduce hip fracture, and increased the risk of kidney stones. ( number, NCT00000611.)

Original languageEnglish
Pages (from-to)669-683
Number of pages15
JournalNew England Journal of Medicine
Issue number7
StatePublished - 16 Feb 2006
Externally publishedYes


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