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Physical Performance). Nineteen studies assessed the association between serum 25OHD concentrations and BMD, and there is fair evidence from observational studies for an association between serum 25OHD concentrations and changes in hip BMD sites. Some studies identified specific serum concentrations of 25OHD below which falls, fractures, or bone loss increased; these values ranged from approximately 40 to 80 nmol/L.

The findings from AHRQ are summarized by DRI-relevant life stage groups in Box 4-5.


Fractures in postmenopausal women and older men: Vitamin D supplementation with or without calcium3 Overall, AHRQ-Ottawa concluded that supplementation with vitamin D (most studies used vitamin D3) plus calcium is effective in reducing fractures in institutionalized older populations. AHRQ-Tufts did not identify new RCTs examining the combined effect of vitamin D plus calcium supplementation on fractures in postmenopausal women and older men.

As reported by AHRQ-Ottawa, 15 RCTs evaluated the effect of vitamin D2 or vitamin D3 (with or without calcium supplementation) on fractures in postmenopausal women and older men (Table 4-11). The majority of the trials used vitamin D3 preparations (300 to 800 IU/day). Ten trials were of higher quality, although high losses to follow-up and inadequate reporting of allocation concealment were limitations of a number of trials. Vertebral fractures were not included as an outcome in most trials. Vitamin D3 (700 to 800 IU/day) combined with calcium supplements (500 to 1,200 mg/day) significantly reduced non-vertebral and hip fractures although the benefit was predominantly in older subjects living in institutionalized settings (hip fractures: odds ratio [OR] = 0.69; 95% CI 0.53–0.90). The benefit of vitamin D and calcium on fractures in community-dwelling individuals was inconsistent across trials.

Specifically, AHRQ-Ottawa conducted a meta-analysis of 13 of the RCTs (omitting Anderson et al. [2004], which is an abstract only, and Larsen et al. [2004], which included no placebo control). Included in the 13 RCTs was the report from Jackson et al. (2006), which reflected data from the WHI trials based on 36,282 subjects. Reproduced in Figures 4-5 through 4-7 are the relevant forest plots for the outcomes related to total fractures from studies that used either oral vitamin D3 or vitamin D2 plus or minus calcium versus calcium or placebo, total fractures for studies that used vitamin D3 plus calcium versus placebo, and hip fractures (by setting)

3

As an aside, it was noted that one RCT of premenopausal women, ages 17 to 35 years, showed that 800 IU/day of vitamin D in combination with 2,000 mg/day of calcium supplementation can reduce the risk of stress fracture from military training compared with placebo (Lappe et al., 2008).



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