2,100 mg/day for the experimental group. The mean baseline intake for vitamin D was about 365 IU/day, which, when combined with the vitamin D supplement, resulted in an approximate vitamin D intake of 765 IU/day for the experimental group. The rate of adherence (defined as use of 80 percent or more of the assigned study supplements) ranged from 60 to 63 percent during the first 3 years of follow-up, with an additional 13 to 21 percent of the participants taking at least half of their study pills. At the end of the trial, 76 percent were still taking the study supplements, and 59 percent were taking 80 percent or more of the supplements.
Among the healthy postmenopausal women in the WHI study, the doses of calcium and vitamin D resulted in an increased risk (17 percent) of kidney stones. Kidney stones were reported by 449 women in the supplemented group, compared with 381 women in the placebo group. With respect to the intention to treat, the reported hazard ratio (HR) was 1.17 (95% CI: 1.02–1.34). Although this study did not focus on calcium intake alone, the total vitamin D intakes were around 800 IU/day, a level that is not associated with either hypercalcemia or hypercalciuria. Therefore, it is reasonable to consider the possibility that total calcium intake of 2,100 mg per day were associated with increased kidney stones in this population. Although the kidney stone events were not adjudicated specifically, adjudication problems should be randomly distributed and thus not a contributing factor to the outcome.
The WHI reflects a large, well-designed cohort study. There is also a report from a small, short trial (covering 4 years) of 236 elderly women with a baseline calcium intake of 800 mg/day and with calcium supplementation of 1,600 mg/day for 1 year (total calcium intake of approximately 2,400 mg/day) (Riggs et al., 1998). In this study, 50 percent of subjects receiving supplemental calcium and 8 percent of placebo controls had urinary calcium levels exceeding 350 mg/day, but no subjects in the calcium group experienced nephrolithiasis, nephrocalcinosis, or a decrease in glomerular filtration rate. Other smaller trials among older subjects have shed little light on the issue of nephrolithiasis and calcium intake, either because the doses were relatively low or because subjects were recruited on the basis of having had previous incidence of kidney stones (Levine et al., 1994; Williams et al., 2001; Borghi et al., 2002).
Curhan et al. (1997) examined the risk for kidney stones in women 34 to 59 years of age, using data from the Nurses’ Health Study (NHS), a notably younger group of subjects than those included in the WHI study. They reported an inverse association between calcium intake from foods, but a positive relationship between risk and intake of calcium from supplements (Curhan et al., 1997). In a 2004 study, Curhan and colleagues (Curhan et al., 2004) prospectively examined data again from the NHS for an 8-year period relative to dietary factors and the risk for kidney stones in women 27 to 44 years of age. In this analysis, the inverse relationship between calcium