SummaryThe 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.IntroductionThis 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.MethodsWHI 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).ResultsAmong 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.ConclusionThough 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.Electronic supplementary materialThe online version of this article (doi:10.1007/s00198-012-2224-2) contains supplementary material, which is available to authorized users.

Incidence rates for liver cancer have increased threefold since the mid-1970s in the United States in parallel with increasing trends for obesity and type 2 diabetes mellitus (T2DM). We conducted an analysis of baseline body mass index (BMI), waist circumference (WC), and T2DM with risk of liver cancer. The Liver Cancer Pooling Project maintains harmonized data from 1.57 million adults enrolled in 14 U.S.-based prospective studies. Cox regression estimated hazard ratios (HR) and 95% confidence intervals (CI) adjusted for age, sex, study center, alcohol, smoking, race, and BMI (for WC and T2DM). Stratified analyses assessed whether the BMI-liver cancer associations differed by hepatitis sera-positivity in nested analyses for a subset of cases (n=220) and controls (n=547). After enrollment, 2,162 incident liver cancer diagnoses were identified. BMI, per 5 kg/m2, was associated with higher risks of liver cancer, more so for men (HR: 1.38; 95% CI: 1.30 to 1.46) than women (HR: 1.25; 95% CI: 1.17 to 1.35; p-interaction: 0.02). WC, per 5 cm, was associated with higher risks of liver cancer, approximately equally by sex (overall, HR: 1.08; 95% CI: 1.04 to 1.13). T2DM was associated with higher risk of liver cancer (HR: 2.61; 95% CI: 2.34 to 2.91). In stratified analyses, there was a null association between BMI and liver cancer risk for participants who were sera-positive for hepatitis. This study suggests that high BMI, high WC, and T2DM are associated with higher risks of liver cancer and that the association may differ by status of viral hepatitis infection.

Associations between anthropometric indices of obesity and breast cancer risk may fail to capture the true relationship between excess body fat and risk. We used dual-energy-X-ray-absorptiometry- (DXA-) derived measures of body fat obtained in the Women's Health Initiative to examine the association between body fat and breast cancer risk; we compared these risk estimates with those for conventional anthropometric measurements. The study included 10,960 postmenopausal women aged 50–79 years at recruitment, with baseline DXA measurements and no history of breast cancer. During followup (median: 12.9 years), 503 incident breast cancer cases were diagnosed. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated using Cox proportional hazards models. All baseline DXA-derived body fat measures showed strong positive associations with breast cancer risk. The multivariable-adjusted HR for the uppermost quintile level (versus lowest) ranged from 1.53 (95% CI 1.14–2.07) for fat mass of the right leg to 2.05 (1.50–2.79) for fat mass of the trunk. Anthropometric indices (categorized by quintiles) of obesity (BMI (1.97, 1.45–2.68), waist circumference (1.97, 1.46–2.65), and waist : hip ratio (1.91, 1.41–2.58)) were all strongly, positively associated with risk and did not differ from DXA-derived measures in prediction of risk.

After completing this course, the reader will be able to:1. Describe the prevalence of bone loss with androgen deprivation therapy for prostate cancer.2. Discuss the possible increased risk of cardiovascular disease and of advanced prostate cancer with high calcium intake.This article is available for continuing medical education credit at CME.TheOncologist.com. CME CME ABSTRACTBackground. Loss of bone mineral density is an unintended consequence of androgen deprivation therapy in men with prostate cancer. Supplementation with calcium and/or vitamin D in these men seems logical and is advocated by many lay and professional groups. Methods. We reviewed guidelines for calcium and vitamin D supplementation and the results of clinical trials of calcium and vitamin D supplementation on bone mineral density in men with prostate cancer undergoing androgen deprivation therapy.Results. Whether supplementation of men undergoing androgen deprivation therapy with calcium and/or vitamin D results in higher bone mineral density than no supplementation has not been tested. The results of 12 clinical

An unintended consequence of breast cancer therapies is an increased risk of osteoporosis due to accelerated bone loss. We conducted a systematic review of calcium and/or vitamin D (Ca±D) supplementation trials for maintaining bone mineral density (BMD) in women with breast cancer using the “before-after” data from the Ca±D supplemented comparison group of trials evaluating the effect of drugs such as bisphosphonates on BMD. Whether Ca±D supplements increase BMD in women undergoing breast cancer therapy has never been tested against an unsupplemented control group. However, results from 16 trials indicate that the Ca±D doses tested (500-1500 mg calcium; 200-1000 IU vitamin D) were inadequate to prevent BMD loss in these women. Cardiovascular disease is the main cause of mortality in women with breast cancer. Because calcium supplements may increase cardiovascular disease risk, future trials should evaluate the safety and efficacy of Ca±D supplementation in women undergoing breast cancer therapy.