title: Health risks and benefits from calcium and vitamin D supplementation: Women's Health Initiative clinical trial and cohort study.
abstract: CONCLUSIONS
  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 D(3) 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.
  
  
  BACKGROUND
  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.
  
  
  METHODS
  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).
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109-1024, USA. rprentic@whi.org
authors.forename: R L
authors.initials: RL
authors.lastname: Prentice
authors.forename: M B
authors.initials: MB
authors.lastname: Pettinger
authors.forename: R D
authors.initials: RD
authors.lastname: Jackson
authors.forename: J
authors.initials: J
authors.lastname: Wactawski-Wende
authors.forename: A Z
authors.initials: AZ
authors.lastname: Lacroix
authors.forename: G L
authors.initials: GL
authors.lastname: Anderson
authors.forename: R T
authors.initials: RT
authors.lastname: Chlebowski
authors.forename: J E
authors.initials: JE
authors.lastname: Manson
authors.forename: L
authors.initials: L
authors.lastname: Van Horn
authors.forename: M Z
authors.initials: MZ
authors.lastname: Vitolins
authors.forename: M
authors.initials: M
authors.lastname: Datta
authors.forename: E S
authors.initials: ES
authors.lastname: LeBlanc
authors.forename: J A
authors.initials: JA
authors.lastname: Cauley
authors.forename: J E
authors.initials: JE
authors.lastname: Rossouw
mesh_terms: D000368:Aged; D050071:Bone Density Conservation Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002119:Calcium Carbonate / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000517:prevention & control; D002762:Cholecalciferol / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D019587:Dietary Supplements / Q000009:adverse effects*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D006620:Hip Fractures / Q000453:epidemiology / Q000209:etiology / Q000517:prevention & control; D006801:Humans; D008875:Middle Aged; D009369:Neoplasms / Q000453:epidemiology / Q000517:prevention & control; D015663:Osteoporosis, Postmenopausal / Q000150:complications / Q000188:drug therapy / Q000453:epidemiology; D058866:Osteoporotic Fractures / Q000453:epidemiology / Q000517:prevention & control*; D018570:Risk Assessment / Q000379:methods; D014481:United States / Q000453:epidemiology; D014545:Urinary Calculi / Q000139:chemically induced / Q000453:epidemiology
chemical_list: D050071:Bone Density Conservation Agents; D002762:Cholecalciferol; D002119:Calcium Carbonate