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BMD was measured for some of the subjects. On average, the background intake of these women provided a relatively high intake of calcium (average 1,150 mg/day), compared with that typically reported for the general population. With the addition of the supplement given as part of the study protocol, calcium intakes approached 2,150 mg/day. Overall, following the intervention, the authors found a small, but significant, improvement in hip BMD; however, the study did not demonstrate a reduction in hip fracture. This appears to be consistent with the understanding that fracture risk is less prevalent under the age of 70 years, particularly among persons 50 to 60 years of age. On the basis of age stratification, women 50 to 59 years of age showed a hazard ratio for hip fracture of 2.17, whereas the HR for women 60 to 69 years of age was 0.74. It is notable that the vitamin D supplementation was relatively low, thereby enhancing the ability to consider the effects of calcium per se. Under these conditions, there is the suggestion that calcium intakes of 2,150 mg/day increased BMD slightly compared with intakes of 1,150 mg/day (placebo with background diet). However, the calcium–vitamin D treatment was associated with an increased risk of kidney stones.

Several studies (Table 4-15) are noted in the context of examining the effect of calcium on BMD at times when menopause occurs or is on-going. As shown in the table, the data suggest mixed results. None measured the nature of the dose–response relationship. Some indicate benefit at lower levels of calcium intake, whereas others show no effect at higher levels of intake. The benefits vary by bone site, but not consistently; and lifestyle factors, such as exercise, appear to be related to outcome. However, the meta-analysis of Shea et al. (2002), which examined calcium supplementation with minimal vitamin D intake, suggested a relatively small, but consistent, effect of calcium supplementation on BMD in postmenopausal women, many of whom were less than 70 years of age. The authors reported that the inference that calcium increases bone density for this group was strengthened by the consistency of the findings across four sites of measurement, but pointed out that loss to follow-up and unexplained heterogeneity confounded the conclusions. In a study of free-living menopausal women that measured total body calcium (by neutral activation analysis), a retardation of bone loss in the femoral neck in early menopause was reported with a calcium intake of 1,700 mg/day (Aloia et al., 1994). However, the study protocol combined the calcium supplementation with 400 IU of vitamin D per day. In contrast, in some studies focused on reducing bone loss in menopausal women using various treatments including increased calcium intake, it was found that the retardation of bone loss with calcium intake was not equivalent to that associated with hormone replacement therapy, but also that it appeared to have minimal effect on retarding that compo-

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