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

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.

© The Author(s) 2020. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Figures

Figure 1.

Total 25(OH)D (2-A) and bioavailable and free 25(OH)D (2-B) levels at 0, 6, and 12 months divided by vitamin D supplementation with high dose and low dose. Asterisk (*) placed between 6 months and 12 months values indicate significant difference between high-dose and low-dose supplementation. There was a significant increase of total (ng/mL), bioavailable (μg/L), and free 25(OH)D (ng/L) at 6 and 12 months compared to values at baseline using repeated-measures ANOVA within each treatment arm.

Figure 2.

Relationship between total 25(OH)D (ng/mL) with free (ng/L) or bioavailable 25(OH)D (μg/L). The values of bioavailable and free 25(OH)D were significantly associated with total 25(OH)D (P value < 0.001), with estimated r2 values of 0.887 and 0.889, respectively.

Figure 3.

The relationship between serum PTH and 25 (OH)D expressed as A, total 25(OH)D; B, bioavailable 25(OH)D; and C, free 25(OH)D, each divided into their respective quartiles. Asterisk (*) indicates significantly lower PTH levels in fourth quartile of serum total, bioavailable, and free 25(OH)D compared with the first quartile.