2006) did not confirm a consistent benefit on BMD or BMC across skeletal sites and age groups. Some studies included combinations of calcium and vitamin D.

There were seven studies in older children and adolescents (two RCTs, three cohort studies, one case–control study, and one before-and-after study) that evaluated the relationship between serum 25OHD concentrations and BMC or BMD (see Table 4-6). In older children, there was one RCT, one prospective cohort study, and one before-and-after study. The RCT (Ala-Houhala et al., 1988) did not find an association between serum 25OHD concentrations and distal radial BMC. Two of three non-RCT studies found a positive association between baseline serum 25OHD concentrations and BMC or BMD. The effect of bone size and muscle mass on these outcomes in relation to baseline serum 25OHD concentrations was not reported.

One RCT with children and adolescent girls (El-Hajj Fuleihan et al., 2006) demonstrated a significant relationship between baseline serum 25OHD concentrations and baseline BMD of the lumbar spine, femoral neck, and radius. However, only high dose supplementation with 14,000 IU of vitamin D₃ per week increased BMC of the total hip.

AHRQ-Tufts identified two RCTs available after the AHRQ-Ottawa analysis, both rated C, that compared the effect of vitamin D supplementation alone on BMC in healthy girls between 10 and 17 years of age (El-Hajj Fuleihan et al., 2006; Andersen et al., 2008). Both RCTs were rated C because the results were not adjusted for important potential confounders, such as height, bone area, lean mass, sun exposure, and pubertal status. One RCT (Andersen et al., 2008) analyzed 26 healthy girls, who were Pakistani immigrants primarily living in the Copenhagen area of Denmark (latitude 55°N). Girls were randomly assigned to receive either a daily dose of 400 or 800 IU of vitamin D₃ or placebo for 1 year. The mean baseline dietary calcium intake was 510 mg/day, and the serum 25OHD concentration was 11 nmol/L. At the end of the study, there were no significant differences in whole-body BMC changes between groups receiving the two doses of vitamin D₃ (400 or 800 IU/day) and the placebo group. A second RCT (El-Hajj Fuleihan et al., 2006) analyzed 168 healthy girls living in the Greater Beirut area, Lebanon (latitude 33°N). Girls were randomly assigned to receive either weekly oral vitamin D doses of 1,400 IU (equivalent to 200 IU/day) or 14,000 IU (equivalent to 2,000 IU/day) or placebo for 1 year. The mean baseline dietary calcium intake was 677 mg/day, and the 25OHD concentration was 35 nmol/L. At the end of the study, there were no significant differences in whole-body BMC changes between either the low-dose vitamin D group (200 IU/day) or the high-dose vitamin D group (2,000 IU/day) and the placebo group. The same findings were seen when analyses were restricted to either premenarcheal or postmenarcheal girls.