Calcium plus vitamin D supplementation and mortality in postmenopausal women: the Women's Health Initiative calcium-vitamin D randomized controlled trial.
BACKGROUND
Calcium and vitamin D (CaD) supplementation trials including the Women's Health Initiative (WHI) trial of CaD have shown nonsignificant reductions in total mortality. This report examines intervention effects on total and cause-specific mortality by age and adherence.


METHODS
The WHI CaD trial was a randomized, double-blind, placebo-controlled trial that enrolled 36,282 postmenopausal women aged 51-82 years from 40 U.S. clinical centers. Women were assigned to 1,000 mg of elemental calcium carbonate and 400 IU of vitamin D(3) daily or placebo with average follow-up of 7.0 years.


RESULTS
The hazard ratio (HR) for total mortality was 0.91 (95% confidence interval [CI], 0.83-1.01) with 744 deaths in women randomized to CaD versus 807 deaths in the placebo group. HRs were in the direction of reduced risk but nonsignificant for stroke and cancer mortality, but near unity for coronary heart disease and other causes of death. HRs for total mortality were 0.89 in the 29,942 women younger than 70 years (95% CI, 0.79-1.01) and 0.95 in the 6,340 women aged 70 and older (95% CI, 0.80-1.12; p value for age interaction = .10). No statistically significant interactions were observed for any baseline characteristics. Treatment effects did not vary significantly by season.


CONCLUSIONS
In the WHI CaD trial, supplementation did not have a statistically significant effect on mortality rates but the findings support the possibility that these supplements may reduce mortality rates in postmenopausal women. These data can neither support nor refute recommendations for higher dose vitamin D supplementation to reduce cancer or total mortality.
LaCroix
Andrea Z
AZ
WHI Clinical Coordinating Center, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, M3-A410, PO Box 19024, Seattle, WA 98109-1024, USA. alacroix@whi.org
Kotchen
Jane
J
Anderson
Garnet
G
Brzyski
Robert
R
Cauley
Jane A
JA
Cummings
Steven R
SR
Gass
Margery
M
Johnson
Karen C
KC
Ko
Marcia
M
Larson
Joseph
J
Manson
JoAnn E
JE
Stefanick
Marcia L
ML
Wactawski-Wende
Jean
J
D000368:Aged; D000369:Aged, 80 and over; D050071:Bone Density Conservation Agents / Q000008:administration & dosage*; D002118:Calcium / Q000008:administration & dosage*; D019587:Dietary Supplements; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008875:Middle Aged; D009026:Mortality; D017698:Postmenopause; D016896:Treatment Outcome; D014807:Vitamin D / Q000008:administration & dosage*; D016387:Women's Health
D050071:Bone Density Conservation Agents; D014807:Vitamin D; D002118:Calcium