Osteoporos Int. doi:10.​1007/​s00198-012-2046-2″
“Introduction

The Women’s Health Initiative (WHI) double-blind, placebo-controlled clinical trial (CT) 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 (CaD) supplementation in a population in which the use of these supplements was widespread would reduce Selleck Protease Inhibitor Library hip fracture, and secondarily, total fracture and colorectal cancer. Even though CaD led to a significantly higher hip and total body bone mineral density than placebo (P < 0.01), there was no compelling evidence for hip or total fracture risk reduction

[1]. Among women who adhered to study FGFR inhibitor medications, however, there was a lower hip fracture incidence in the intervention group [1], though this type of adherence-adjusted analysis involves additional modeling assumptions and lacks the reliability of the corresponding intention-to-treat analysis. Additional analyses led to reports of no clear evidence of benefit or harm for colorectal cancer [2], breast cancer [3], or other invasive cancer [4], though the possibility of a breast cancer risk reduction among women using little or no personal calcium supplements was noted [3]. Additional reports noted no clear evidence of influence on coronary heart disease (CHD) risk, defined in WHI and here as nonfatal myocardial infarction (MI) or CHD death [5], and to the possibility of a reduction in total mortality [6]. A modest elevation in urinary tract stone occurrence in the intervention group was also observed [1, 7]. The WHI trial has been criticized in that participating women were allowed to continue their

personal use of calcium and/or vitamin D, in addition to taking study pills [8]. Our perspective, as WHI investigators, is that the question of health risks and benefits associated with CaD supplementation, beyond the use of personal supplements, is of direct importance to Vildagliptin postmenopausal women in the general population. We agree, however, that subset analyses restricted to women not taking personal supplements are of considerable interest from both etiologic and public health perspectives. Bolland et al. [8] reanalyzed WHI CaD trial data and reported an interaction (P = 0.04) in hazard ratio (HR) for “clinical MI” according to whether or not women were not using personal calcium supplements at baseline. A similar interaction was reported for combined clinical MI and stroke.