Response to an adequate dietary intake of vitamin D3 modulates the effect of estrogen therapy on bone density

This study analyzed associations between plasma vitamin D(3) (25OHD(3)) and bone mineral density (BMD) and whether the effects of conjugated equine estrogens (CEE) on BMD are modulated by 25OHD(3). Fifty cynomolgus monkeys were fed a diet containing 25OHD(3) (providing a woman's equivalent of 1000 IU/day of 25OHD3). The monkeys underwent bilateral oophorectomy and were randomized to either CEE (equivalent of 0.45 mg/day) (n=25) or placebo (n=25) and continued receiving the same diet. 25OHD(3) and BMD were measured at randomization and after 6 months. BMD also was measured after 20 months (equivalent to 6 human years). Associations between 25OHD(3) and BMD were subsequently analyzed. Baseline 25OHD(3) plasma concentrations varied from 26 to 95 ng/mL (mean±standard deviation [SD] 54 ± 15 ng/mL). Higher plasma concentrations of 25OHD(3) were associated with a significantly increased BMD. Monkeys on both CEE and placebo had increased BMD over 20 months; however, the increase was not significantly different (0.034 g/cm(2) vs. 0.020 g/cm(2), respectively; p=0.064). The 20-month BMD increased significantly with CEE treatment in those with higher vs. lower 25OHD(3) concentrations (p=0.027). The percent change in BMD over 20 months also increased significantly with CEE treatment in those with higher vs. lower 25OHD(3) concentrations (p=0.018). A higher 25OHD(3) concentration had no significant effect on BMD in those receiving placebo. Monkeys fed a diet containing 1000 IU/day equivalent of 25OHD(3) have a wide range of plasma 25OHD(3) concentrations. Those receiving CEE with higher 25OHD(3) concentrations had higher BMDs, suggesting 25OHD(3) and CEE have synergistic effects on BMD.