Effect of increasing doses of vitamin D on bone mineral density and serum N‐terminal telopeptide in elderly women: a randomized controlled trial

Background There are few controlled studies of the effect of different doses of vitamin D3 on bone mineral density (BMD). Objectives We conducted a randomized placebo‐controlled trial of increasing doses of vitamin D3 in 163 Caucasian and 31 African American women with serum 25‐hydroxyvitamin D (25OHD) ≤50 nmol/L. This is an analysis of secondary outcome BMD to see if there is an association between percent change in BMD and dose of vitamin D3. Methods Participants were randomly assigned to placebo, vitamin D3 400, 800, 1600, 2400, 3200, 4000, or 4800 IU/day; calcium supplements, average 600mg, were given to provide a total calcium intake of 1200 mg/d. The primary outcome was 12‐month serum 25OHD level. Analysis methods include ANOVA and Pearson correlations. Results The mean percent increase (±SD) in BMD at 12 months for all women was small; total body, 0.62% (± 2.72), femoral neck 0.59% (±3.58) and spine 0.43% (±2.80). There was no difference in BMD or serum N‐telopeptide in response to vitamin D by dose or race. The increase in total body, spine and hip BMD in elderly women given vitamin D doses between 400 and 4800 IU daily and calcium supplementation is small, unrelated to dose or 12‐month serum 25OHD, free 25OHD or 1,25(OH)2D. There was no evidence of a threshold change in BMD with increasing serum 25OHD or free 25OHD in this population. Conclusions We found no significant effect of daily vitamin D dose ranging from 400 to 4800 IU/day on BMD or serum N‐terminal telopeptides in elderly women with initially low serum 25OHD.