femoral neck and total hip. Based on included trials, it was less certain whether vitamin D3 supplementation alone has a significant effect on BMD.
Seventeen RCTs evaluated the effect of supplemental vitamin D2 or vitamin D3 on BMD, predominantly in populations of late menopausal women (see Table 4-8). Only one small RCT included premenopausal women, and two trials included older men (> 60 years). Most trials were 2 to 3 years in duration and used vitamin D doses of up to 800 IU daily. Most trials used vitamin D3 and also included 500 mg of calcium as a co-intervention.
Meta-analysis results of 17 RCTs comparing vitamin D3 plus calcium with placebo (AHRQ-Tufts) were consistent with a small effect on lumbar spine, femoral neck, and total body BMD. The WHI trial found a significant benefit of supplementation with 400 IU of vitamin D3 plus 1,000 mg of calcium on total hip BMD. However, when the effect of supplementation with vitamin D3 plus calcium versus supplementation with calcium alone was assessed by AHRQ-Tufts, no significant increase in BMD was observed with either intervention, suggesting that vitamin D3 may be of less benefit in calcium-replete postmenopausal women. It is noted, however, that the dose administered was 400 IU/day, which is a lower level than has been used commonly, although the authors of the report did measure background intakes of vitamin D for participants, which, when added to the 400 IU dose results in an average intake of approximately 750 IU/day. Vitamin D3 alone versus placebo did not result in a significant increase in BMD in postmenopausal women, except in one trial that noted an increase in femoral neck BMD. Only a few trials reported the impact of baseline serum 25OHD concentrations on BMD; in all of these trials, baseline 25OHD concentration was not associated with increased BMD.
AHRQ-Tufts identified four RCTs that were made available after the completion of AHRQ-Ottawa, one of which focused on children (see Table 4-9). Two of the three new RCTs for women and elderly men indicated a significant increase in hip or total BMD in postmenopausal women, comparing vitamin D3 or vitamin D2 (300 or 1,000 IU/day, respectively) plus calcium (1,200 mg/day) with placebo. The RCT that focused on healthy girls, ages 10 to 12 years (Cheng et al., 2005) compared the effect of vitamin D3 (200 IU/day) plus calcium (1,000 mg/day) supplementation on bone indexes with placebo. The mean background dietary calcium intake was 670 mg/day. The intention-to-treat analyses suggested that after 2 years of supplementation, there was no significant difference in the BMC changes between girls who received vitamin D plus calcium supplement or placebo. The methodological quality of this study was rated C, as a result of being underpowered and having low compliance rate. The findings from AHRQ are summarized by DRI-relevant life stage groups in Box 4-4.