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ship between the two nutrients and bone health is more appropriately explored by examining evidence from controlled interventions, although data from observational studies can lend support and offer confirmatory input. Observational data regarding calcium intake and bone health are mixed regarding the finding that a range of increasing calcium intakes above deficiency levels are associated with improved bone mass and reduced fracture risk. These studies are confounded by an array of variables that have an impact on measures of bone density.

Regarding serum 25OHD concentrations and bone health, the AHRQ-Ottawa analysis concluded that observational studies suggested a correlation between higher serum 25OHD concentrations and increased BMC for older children and adolescents. For postmenopausal women and elderly men, observational studies reviewed in AHRQ-Ottawa provided fair evidence to support an association between serum 25OHD level and BMD or changes in BMD at the femoral neck. This analysis noted that the observational data overall were discordant with the results from available RCTs. Newer observational studies for the most part are consistent with older observational studies with respect to a relationship between low serum 25OHD levels and outcomes such as bone loss, fractures, or osteomalacia (Cauley et al., 2008; Looker and Mussolino, 2008; van Schoor et al., 2008; Ensrud et al., 2009; Bolland et al., 2010b; Cauley et al., 2010; Melhus et al., 2010). However, there are confounders related to such studies, including age, calcium intake, and social situation.

Bone mineral content/bone mineral density: Serum 25OHD AHRQ conducted its analyses for serum 25OHD concentrations on the basis of certain age and gender groups, as presented below.

Infants Overall, AHRQ-Ottawa, for which some studies included combinations of calcium and vitamin D, has reported that there is inconsistent evidence for an association between serum 25OHD concentrations and BMC measures in infants. Of the two RCTs examining BMC (Greer et al., 1982; Zeghoud et al., 1997), one demonstrated no significant benefit of higher serum 25OHD concentrations on radial bone mass, whereas the other showed a transient increase of BMC compared with the unsupplemented group at 12 weeks, but not at 26 weeks. Based on case–control studies (Okonofua et al., 1986; Bougle et al., 1998; Namgung et al., 1998; Park et al., 1998), greater whole-body BMC was related to higher serum 25OHD levels. Data are summarized in Table 4-5. AHRQ-Tufts found no additional RCTs for infants published in the period since the completion of the AHRQ-Ottawa review.

Children and adolescents For children and adolescents, there was fair evidence from AHRQ-Ottawa of an association between serum 25OHD levels and baseline BMD and change in BMD or BMD indexes. However, the results from the RCTs (Ala-Houhala et al., 1988; El-Hajj Fuleihan et al.,

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