Original Article

Osteoporosis International

, Volume 24, Issue 2, pp 567-580

First online:

Open Access This content is freely available online to anyone, anywhere at any time.

Health risks and benefits from calcium and vitamin D supplementation: Women's Health Initiative clinical trial and cohort study

  • R. L. PrenticeAffiliated withFred Hutchinson Cancer Research CenterPublic Health Sciences Division, Fred Hutchinson Cancer Research Center Email author 
  • , M. B. PettingerAffiliated withFred Hutchinson Cancer Research Center
  • , R. D. JacksonAffiliated withOhio State University
  • , J. Wactawski-WendeAffiliated withState University of New York
  • , A. Z. LaCroixAffiliated withFred Hutchinson Cancer Research Center
  • , G. L. AndersonAffiliated withFred Hutchinson Cancer Research Center
  • , R. T. ChlebowskiAffiliated withLos Angeles Biomedical Research Institute at Harbor-UCLA Medical Center
  • , J. E. MansonAffiliated withBrigham and Women’s Hospital, Harvard Medical School
  • , L. Van HornAffiliated withNorthwestern University
    • , M. Z. VitolinsAffiliated withWake Forest University Health Sciences
    • , M. DattaAffiliated withWake Forest University Health Sciences
    • , E. S. LeBlancAffiliated withKaiser Permanente Center for Health Research
    • , J. A. CauleyAffiliated withGraduate School of Public Health, University of Pittsburgh
    • , J. E. RossouwAffiliated withFred Hutchinson Cancer Research CenterNational Heart, Lung and Blood Institute, National Institutes of Health



The Women's Health Initiative (WHI) double-blind, placebo-controlled clinical trial randomly assigned 36,282 postmenopausal women in the U.S. to 1,000 mg elemental calcium carbonate plus 400 IU of vitamin D3 daily or placebo, with average intervention period of 7.0 years. The trial was designed to test whether calcium plus vitamin D supplementation in a population in which the use of these supplements was widespread would reduce hip fracture, and secondarily, total fracture and colorectal cancer.


This study further examines the health benefits and risks of calcium and vitamin D supplementation using WHI data, with emphasis on fractures, cardiovascular disease, cancer, and total mortality.


WHI calcium and vitamin D randomized clinical trial (CT) data through the end of the intervention period were further analyzed with emphasis on treatment effects in relation to duration of supplementation, and these data were contrasted and combined with corresponding data from the WHI prospective observational study (OS).


Among women not taking personal calcium or vitamin D supplements at baseline, the hazard ratio [HR] for hip fracture occurrence in the CT following 5 or more years of calcium and vitamin D supplementation versus placebo was 0.62 (95 % confidence interval (CI), 0.38–1.00). In combined analyses of CT and OS data, the corresponding HR was 0.65 (95 % CI, 0.44–0.98). Supplementation effects were not apparent on the risks of myocardial infarction, coronary heart disease, total heart disease, stroke, overall cardiovascular disease, colorectal cancer, or total mortality, while evidence for a reduction in breast cancer risk and total invasive cancer risk among calcium plus vitamin D users was only suggestive.


Though based primarily on a subset analysis, long-term use of calcium and vitamin D appears to confer a reduction that may be substantial in the risk of hip fracture among postmenopausal women. Other health benefits and risks of supplementation at doses considered, including an elevation in urinary tract stone formation, appear to be modest and approximately balanced.


Calcium Cancer Cardiovascular disease Fractures Health risks and benefits Vitamin D