Journal Article

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

Pettinger, M. B., Chlebowski, R. T., Manson, J. E., Anderson, G. L., Van Horn, L., Vitolins, M. Z., Cauley, J. A., Datta, M., LaCroix, A. Z., Rossouw, J. E., Jackson, R. D., LeBlanc, E. S., Prentice, R. L., Wactawski-Wende, J.

2013

Overview

Summary 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. Introduction 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. Conclusion 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.

• Publisher: Springer-Verlag,Springer Nature B.V
• Subject: Aged / Bone Density Conservation Agents - administration & dosage / Bone Density Conservation Agents - adverse effects / Bone Density Conservation Agents - therapeutic use / Breast cancer / Calcium / Calcium Carbonate - administration & dosage / Calcium Carbonate - adverse effects / Calcium Carbonate - therapeutic use / Cancer / Cancer research / Cardiovascular disease / Cardiovascular diseases / Cardiovascular Diseases - epidemiology / Cardiovascular Diseases - prevention & control / Cholecalciferol - administration & dosage / Cholecalciferol - adverse effects / Cholecalciferol - therapeutic use / Clinical trials / Cohort analysis / Colorectal cancer / Colorectal carcinoma / Coronary heart disease / Cost-benefit analysis / Data processing / Dietary supplements / Dietary Supplements - adverse effects / Double-Blind Method / Drug Administration Schedule / Drug Therapy, Combination / Endocrinology / Female / Fractures / Health risk assessment / Health risks / Health sciences / Heart attacks / Heart diseases / Hip / Hip fracture / Hip Fractures - epidemiology / Hip Fractures - etiology / Hip Fractures - prevention & control / Hip joint / Humans / Intervention / Invasiveness / Medical research / Medicine / Medicine & Public Health / Middle Aged / Mortality / Neoplasms - epidemiology / Neoplasms - prevention & control / Original / Original Article / Orthopedics / Osteoporosis, Postmenopausal - complications / Osteoporosis, Postmenopausal - drug therapy / Osteoporosis, Postmenopausal - epidemiology / Osteoporotic Fractures - epidemiology / Osteoporotic Fractures - prevention & control / Post-menopause / Public health / Rheumatology / Risk Assessment - methods / Stroke / Supplementation / United States - epidemiology / Urinary Calculi - chemically induced / Urinary Calculi - epidemiology / Urinary tract / Urogenital system / Vitamin D / Vitamin D3 / Womens health