Postmenopausal women and elderly men Overall, regarding serum 25OHD and bone density measures, AHRQ-Ottawa, which included some studies that combined calcium and vitamin D, reported discordance between the results from RCTs and the majority of observational studies; the authors attributed this as likely due to the impact of confounders relative to observational data as a general matter. Nineteen studies (see Table 4-7) evaluated the association between serum 25OHD levels and BMD. Of these, six studies were RCTs. One RCT (Ooms et al., 1995b) reported an association between serum 25OHD concentrations and BMD or bone loss, whereas the other five RCTs (Dawson-Hughes et al., 1995; Storm et al., 1998; Schaafsma et al., 2002; Cooper et al., 2003; Aloia et al., 2005) and three cohort studies did not. Four cohort studies found a significant association between 25OHD concentrations and bone loss, which was most evident at the hip sites, but the evidence for an association between 25OHD concentrations and lumbar spine BMD was weak. Six case–control studies suggested an association between 25OHD concentrations and BMD, and the association was most consistent at the femoral neck. A forest plot showing the effect of vitamin D plus calcium supplementation (versus placebo) for femoral neck BMD at 1 year is shown in Figure 4-4. Overall, significant increases at the femoral neck were observed with a combined estimate as reported in Table 4-7 of 1.37 percent (95% confidence interval [CI]: 0.24–2.50) from three trials after 1 year.
Based on the results from the observational studies, there is fair evidence to support an association between serum 25OHD levels and BMD or changes in BMD at the femoral neck. Specific circulating concentrations of 25OHD below which bone loss at the hip was increased ranged from 30 to 80 nmol/L.
AHRQ-Tufts identified two more recent RCTs, one that combined calcium with vitamin D and one that did not. The first, an A-quality RCT (Zhu et al., 2008a), compared the effect of vitamin D2 supplementation on hip BMC in 256 elderly women between 70 and 90 years of age. All elderly women in this trial had normal physical functioning. They were randomly assigned to receive either vitamin D2 (1,000 IU/day) plus calcium (1,200 mg/day) supplement or calcium (1,200 mg/day) supplement alone for 1 year. The mean baseline dietary calcium intake was 1,097 mg/day, and the mean serum 25OHD concentration was 44.3 nmol/L. Total hip BMD increased significantly in both groups, with no difference between the vitamin D2 plus calcium and calcium alone groups (hip BMD change: vitamin D, +0.5 percent; control, +0.2 percent).
The second, a B-quality RCT (Andersen et al., 2008), analyzed 89 healthy adult women and 83 healthy adult men separately. The participants were Pakistani immigrants living in the Copenhagen area of Denmark (latitude 55°N). Women and men were randomly assigned to receive either a daily dose of 400 or 800 IU vitamin D3 or placebo for 1 year. For women,