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lationship between serum 25OHD level and risk for falling and/or poor physical performance in susceptible populations.

Biological Plausibility

Experimental evidence suggests that vitamin D exerts its effect on muscle tissue via the VDR, but it may also use other pathways. In vitro and in vivo experiments provide evidence to support calcitriol regulation of calcium uptake by muscle, which, in turn, controls muscle contraction and relaxation, synthesis of muscle cytoskeletal proteins involved in muscle contraction, and muscle cell proliferation and differentiation (reviewed in Ceglia, 2008). Because intracellular calcium levels control the contraction and relaxation of muscle, thus affecting muscle function, it is possible that calcium intake may also affect risk for falls and poor physical performance (reviewed in Ceglia, 2008). However, the topic is not considered in more detail here because of the lack of observational and RCT data on the relationship between calcium intake and physical performance.

Systematic Reviews and Meta-Analyses

The AHRQ-Ottawa systematic review identified a total of 14 RCTs in addition to five prospective cohort studies and one case–control study that examined vitamin D and risk for falls in postmenopausal women and elderly men. The evidence between the RCTs and observational studies was discordant. Overall the review reported that the evidence for an association between low serum 25OHD levels and risk of falls and measures of physical performance among postmenopausal women and elderly men was inconsistent and rated the evidence as “fair.” The AHRQ-Tufts systematic review identified three additional RCTs (Bunout et al., 2006; Burleigh et al., 2007; Lyons et al., 2007), but these studies did not find a significant effect of vitamin D supplementation on reducing risk of falls or poor performance in the elderly and were given a “C” rating. No additional observational evidence was found for this indicator in the AHRQ-Tufts review.

A meta-analysis reported in AHRQ-Tufts, which included the AHRQ-Ottawa RCTs, highlighted the inconsistency of findings from RCTs on the effect of vitamin D treatment on reduction in risk or prevention of falls. A smaller meta-analysis by Bischoff-Ferrari et al. (2004a) examined RCTs in elderly populations for evidence of a reduction in risk for falls with “vitamin D”; however, only three studies used vitamin D, and the other two studies used calcitriol/1α-hydroxycholecalciferol. Some of the studies identified in this meta-analysis were also included in the AHRQ-Tuft analysis. In contrast to the AHRQ-Tufts analysis, Bischoff-Ferrari et al. (2004a) found, from pooled results, a significant reduction in risk of falling among sub-

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