Total, Bioavailable, and Free 25(OH)D Relationship with Indices of Bone Health in Elderly: A Randomized Controlled Trial

J Clin Endocrinol Metab. 2021 Jan 23;106(2):e990-e1001. doi: 10.1210/clinem/dgaa780.

Abstract

Context: Questions regarding the superiority of free and bioavailable 25-hydroxyvitamin D [25(OH)D] in predicting health outcomes remain unresolved.

Objective: This study investigates the impact of vitamin D variables-total, bioavailable, or free 25(OH)D-on indices of bone and mineral metabolism, at baseline and in response to 2 vitamin D doses.

Design: Our objectives are implemented as exploratory analyses on data collected in a 1-year, double-blind, randomized controlled trial completed in July 2014.

Setting: Participants were recruited from 3 major hospitals in an ambulatory setting.

Participants: Participants were >65 years of age, overweight, and had a baseline serum 25(OH)D between 10 and 30 ng/mL. A total of 221 participants completed the study.

Intervention: Subjects were randomized to receive calcium and oral vitamin D3 (600 IU/day or 3750 IU/day) supplementation.

Results: Participants who received the higher vitamin D dose had levels that were 1.3- to 1.4-fold higher than those taking the lower dose, for all variables (P value < 0.001). Serum values of bioavailable and free 25(OH)D were associated with total 25(OH)D, with r values of 0.942 and 0.943, respectively (P value < 0.001). Parathyroid hormone (PTH) was negatively associated with all vitamin D variables, with correlation coefficients ranging from -0.22 to -0.25, while calcium and bone turnover markers (carboxy-terminal collagen crosslinks and osteocalcin) did not. Only total 25(OH)D had a positive relationship with % change bone mineral density (BMD) at the femoral neck at 12 months, while only free and bioavailable 25(OH) had a positive relationship with % change total body BMD at 12 months.

Conclusion: Calculated free and bioavailable 25(OH)D do not appear to be superior to total 25(OH)D in predicting indices of bone health in an elderly population.

Trial registration: ClinicalTrials.gov NCT01315366.

Keywords: 25(OH)D; PTH; bone markers; elderly; vitamin D.

Publication types

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

MeSH terms

  • Aged
  • Biomarkers / blood*
  • Bone Density*
  • Double-Blind Method
  • Female
  • Follow-Up Studies
  • Humans
  • Male
  • Prognosis
  • Vitamin D / analogs & derivatives*
  • Vitamin D / blood
  • Vitamins / blood*

Substances

  • Biomarkers
  • Vitamins
  • Vitamin D
  • 25-hydroxyvitamin D

Associated data

  • ClinicalTrials.gov/NCT01315366