Calcium plus Vitamin D Supplementation and the Risk of Fractures
Rebecca D. Jackson, M.D., Andrea Z. LaCroix, Ph.D., Margery Gass, M.D., Robert B. Wallace, M.D., John Robbins, M.D., Cora E. Lewis, M.D., Tamsen Bassford, M.D., Shirley A.A. Beresford, Ph.D., Henry R. Black, M.D., Patricia Blanchette, M.D., Denise E. Bonds, M.D., Robert L. Brunner, Ph.D., Robert G. Brzyski, M.D., Bette Caan, Dr.P.H., Jane A. Cauley, Dr.P.H., Rowan T. Chlebowski, M.D., Steven R. Cummings, M.D., Iris Granek, M.D., Jennifer Hays, Ph.D., Gerardo Heiss, M.D., Susan L. Hendrix, D.O., Barbara V. Howard, Ph.D., Judith Hsia, M.D., F. Allan Hubbell, M.D., Karen C. Johnson, M.D., Howard Judd, M.D., Jane Morley Kotchen, M.D., Lewis H. Kuller, M.D., Robert D. Langer, M.D., Norman L. Lasser, M.D., Marian C. Limacher, M.D., Shari Ludlam, M.P.H., JoAnn E. Manson, M.D., Karen L. Margolis, M.D., Joan McGowan, Ph.D., Judith K. Ockene, Ph.D., Mary Jo O'Sullivan, M.D., Lawrence Phillips, M.D., Ross L. Prentice, Ph.D., Gloria E. Sarto, M.D., Marcia L. Stefanick, Ph.D., Linda Van Horn, Ph.D., Jean Wactawski-Wende, Ph.D., Evelyn Whitlock, M.D., Garnet L. Anderson, Ph.D., Annlouise R. Assaf, Ph.D., David Barad, M.D., for the Women's Health Initiative Investigators
Background The efficacy of calcium with vitamin D supplementationfor preventing hip and other fractures in healthy postmenopausalwomen remains equivocal.
Methods We recruited 36,282 postmenopausal women, 50 to 79 yearsof age, who were already enrolled in a Women's Health Initiative(WHI) clinical trial. We randomly assigned participants to receive1000 mg of elemental calcium as calcium carbonate with 400 IUof vitamin D3 daily or placebo. Fractures were ascertained foran average follow-up period of 7.0 years. Bone density was measuredat three WHI centers.
Results Hip bone density was 1.06 percent higher in the calciumplus vitamin D group than in the placebo group (P<0.01).Intention-to-treat analysis indicated that participants receivingcalcium plus vitamin D supplementation had a hazard ratio of0.88 for hip fracture (95 percent confidence interval, 0.72to 1.08), 0.90 for clinical spine fracture (0.74 to 1.10), and0.96 for total fractures (0.91 to 1.02). The risk of renal calculiincreased with calcium plus vitamin D (hazard ratio, 1.17; 95percent confidence interval, 1.02 to 1.34). Censoring data fromwomen when they ceased to adhere to the study medication reducedthe hazard ratio for hip fracture to 0.71 (95 percent confidenceinterval, 0.52 to 0.97). Effects did not vary significantlyaccording to prerandomization serum vitamin D levels.
Conclusions Among healthy postmenopausal women, calcium withvitamin D supplementation resulted in a small but significantimprovement in hip bone density, did not significantly reducehip fracture, and increased the risk of kidney stones. (ClinicalTrials.govnumber, NCT00000611
[ClinicalTrials.gov]
.)
Source Information
Address reprint requests to Dr. Jackson at the Division of Endocrinology, Ohio State University, 485 McCampbell, 1581 Dodd Dr., Columbus, OH 43210, or at jackson.20{at}osu.edu.
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