Response to an Adequate Dietary Intake of Vitamin D 3 Modulates the Effect of Estrogen Therapy on Bone Density

Abstract

Introduction:

This study analyzed associations between plasma 25-hydroxyvitamin D₃ (25OHD₃) and bone mineral density (BMD) and whether the effects of conjugated equine estrogens (CEE) on BMD are modulated by 25OHD₃.

Methods:

Fifty cynomolgus monkeys were fed a diet containing vitamin D₃ (providing a woman's equivalent of 1000 IU/day of vitamin D₃). 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. 25OHD₃ and BMD were measured at randomization and after 6 months. BMD also was measured after 20 months (equivalent to 6 human years). Associations between 25OHD₃ and BMD were subsequently analyzed.

Results:

Baseline 25OHD₃ plasma concentrations varied from 26 to 95 ng/mL (mean±standard deviation [SD] 54 ±  15 ng/mL). Higher plasma concentrations of 25OHD₃ 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/cm² vs. 0.020 g/cm², respectively; p=0.064). The 20-month BMD increased significantly with CEE treatment in those with higher vs. lower 25OHD₃ concentrations (p=0.027). The percent change in BMD over 20 months also increased significantly with CEE treatment in those with higher vs. lower 25OHD₃ concentrations (p=0.018). A higher 25OHD₃ concentration had no significant effect on BMD in those receiving placebo.

Conclusions:

Monkeys fed a diet containing 1000 IU/day equivalent of 25OHD₃ have a wide range of plasma 25OHD₃ concentrations. Those receiving CEE with higher 25OHD₃ concentrations had higher BMDs, suggesting 25OHD₃ and CEE have synergistic effects on BMD.