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

J Womens Health (Larchmt). 2012 Aug;21(8):858-64. doi: 10.1089/jwh.2011.3244. Epub 2012 Jun 12.


Introduction: 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).

Methods: 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.

Results: 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.

Conclusions: 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antifibrinolytic Agents / pharmacology
  • Body Mass Index
  • Bone Density / drug effects*
  • Cholecalciferol / blood
  • Cholecalciferol / therapeutic use*
  • Cohort Studies
  • Dose-Response Relationship, Drug
  • Estradiol / blood
  • Estrogen Replacement Therapy*
  • Estrogens / pharmacology
  • Estrogens / therapeutic use*
  • Estrogens, Conjugated (USP) / pharmacology
  • Estrogens, Conjugated (USP) / therapeutic use*
  • Hemostatics
  • Longitudinal Studies
  • Macaca fascicularis
  • Models, Animal
  • Postmenopause / blood
  • Postmenopause / drug effects
  • Vitamin K 2 / analogs & derivatives*
  • Vitamin K 2 / antagonists & inhibitors
  • Vitamin K 2 / blood
  • Vitamins / therapeutic use*


  • Antifibrinolytic Agents
  • Estrogens
  • Estrogens, Conjugated (USP)
  • Hemostatics
  • Vitamins
  • Vitamin K 2
  • Cholecalciferol
  • menatetrenone
  • Estradiol