title: Calcium plus vitamin D supplementation and health outcomes five years after active intervention ended: the Women's Health Initiative.
abstract: BACKGROUND
  Clinical outcomes of the Women's Health Initiative (WHI) calcium plus vitamin D supplementation trial have been reported during 7.0 years of active intervention. We now report outcomes 4.9 years after the intervention stopped and cumulative findings.
  
  
  METHODS
  Postmenopausal women (N=36,282) were randomized; postintervention follow-up continued among 29,862 (86%) of surviving participants. Primary outcomes were hip fracture and colorectal cancer. Breast cancer, all cancers, cardiovascular disease (CVD), and total mortality were predetermined major study outcomes.
  
  
  RESULTS
  Hip fracture incidence was comparable in the supplement and the placebo groups, postintervention hazard ratio (HR)=0.95, 95% confidence interval (95% CI: 0.78, 1.15) and overall HR=0.91 (95% CI: 0.79, 1.05). Overall, colorectal cancer incidence did not differ between randomization groups, HR=0.95 (95% CI: 0.80, 1.13). Throughout, there also was no difference in invasive breast cancer, CVD, and all-cause mortality between groups. In subgroup analyses, the invasive breast cancer effect varied by baseline vitamin D intake (p=0.03 for interaction). Women with vitamin D intakes >600 IU/d, had an increased risk of invasive breast cancer, HR=1.28 (95% CI; 1.03, 1.60). Over the entire study period, in post hoc analyses, the incidence of vertebral fractures, HR=0.87 (95% CI: 0.76, 0.98) and in situ breast cancers, HR=0.82 (95% CI: 0.68, 0.99) were lower among women randomized to supplementation.
  
  
  CONCLUSIONS
  After an average of 11 years, calcium and vitamin D supplementation did not decrease hip fracture or colorectal cancer incidence. Exploratory analyses found lower vertebral fracture and in situ breast cancer incidence in the supplement users. There was no effect on CVD or all-cause mortality.
authors.affiliation: 1 University of Pittsburgh , Pittsburgh, Pennsylvania.
authors.forename: Jane A
authors.initials: JA
authors.lastname: Cauley
authors.forename: Rowan T
authors.initials: RT
authors.lastname: Chlebowski
authors.forename: Jean
authors.initials: J
authors.lastname: Wactawski-Wende
authors.forename: John A
authors.initials: JA
authors.lastname: Robbins
authors.forename: Rebecca J
authors.initials: RJ
authors.lastname: Rodabough
authors.forename: Zhao
authors.initials: Z
authors.lastname: Chen
authors.forename: Karen C
authors.initials: KC
authors.lastname: Johnson
authors.forename: Mary Jo
authors.initials: MJ
authors.lastname: O'Sullivan
authors.forename: Rebecca D
authors.initials: RD
authors.lastname: Jackson
authors.forename: JoAnn E
authors.initials: JE
authors.lastname: Manson
mesh_terms: D000368:Aged; D001943:Breast Neoplasms / Q000453:epidemiology; D002119:Calcium Carbonate / Q000008:administration & dosage*; D002136:Calcium, Dietary / Q000008:administration & dosage; D002318:Cardiovascular Diseases / Q000453:epidemiology; D019587:Dietary Supplements; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D050723:Fractures, Bone / Q000453:epidemiology; D006801:Humans; D015994:Incidence; D008875:Middle Aged; D017698:Postmenopause; D012959:Socioeconomic Factors; D013997:Time Factors; D016896:Treatment Outcome; D014481:United States; D014807:Vitamin D / Q000008:administration & dosage* / Q000627:therapeutic use; D016387:Women's Health
chemical_list: D002136:Calcium, Dietary; D014807:Vitamin D; D002119:Calcium Carbonate