There is some evidence that the use of calcium in the form of supplements reduces the risk of osteoporosis and resulting fractures, which are serious causes of morbidity for older women. Approximately one-third of cortical bone and one-half of trabecular bone is lost through osteoporosis in postmenopausal women. The rates of bone loss may reach three to five percent per year immediately following menopause, and one percent per year in older women. Although fractures are not a major overall cause of mortality, death from complications of hip fractures (such as thromboembolism, fat embolism, pneumonia, and surgical deaths) are high, and fractures account for much morbidity and dysmobility. The annual incidence of fractures is 0.5 percent of women aged 55-64, doubles to 1 percent of women ages 65-74, and more than doubles again to 2.3 percent in women aged 75-84. Hip fractures will be the primary endpoint for the CaD branch of the CT.

Most women do not have an adequate daily intake of calcium. Postmenopausal women require 1,500 mg per day, yet 75 to 80 percent of women have daily intakes below 800 mg per day (1984 NIH Consensus Conference, referenced in the June 28, 1993 WHI Protocol). The intestinal absorption of calcium declines with age, increasing the probability that calcium in the diet is insufficient to prevent bone loss.

Some investigators have found that the addition of vitamin D increases the effect of supplemental calcium on the prevention of bone loss. It is uncertain if this is because the absorption of calcium is enhanced, or if vitamin D exerts an independent effect on bone (Dawson-Hughes et al., 1991, referenced in the June 28, 1993 WHI Protocol). A subsidiary aim of the CaD branch will be to test the effect of supplementation on bone mineral density. Bone mineral density measurements will be made at only three Vanguard Clinical Centers (it is unclear how many of the additional clinical centers will measure bone mineral density). Changes in bone density over the course of the study will be examined in relation to each branch of the CT.

The CaD branch of the CT is not the primary motivator for the WHI, and it could not stand alone as the justification for the trial. However, it can be justified as part of the CT. In addition, it may provide valuable information on the interaction of CaD supplementation and the DM and HRT interventions. For example, estrogen is known to increase intestinal calcium absorption (as well as reduce renal calculi formation). Therefore, it may be possible to test the hypothesis that HRT and calcium together protect women from osteoporosis. In contrast, low fat diets are frequently low in calcium because of the reduction of dairy foods, and although a reduction of calcium has not been seen in the feasibility studies for the WHI, it will be useful to have a subsample of women in the DM who are also taking calcium.