Racial differences in calculated bioavailable vitamin D with vitamin D/calcium supplementation

Abstract

Objectives Some studies suggest that bioavailable 25-(OH)D is more accurate than total 25-(OH)D as an assessment of vitamin D status in black individuals, We hypothesized that increases in bioavailable 25-(OH)D would correlate better with improvement in bone outcomes among black HIV-infected adults. Design This is a secondary analysis of ACTG A5280, a randomized, double-blind study of Vitamin D3 and calcium (VitD/Ca) supplementation in HIV-infected participants initiating antiretroviral therapy (ART). Methods Effect of VitD/Ca on total and calculated bioavailable 25-(OH)D, parathyroid hormone (PTH), bone turnover markers (BTMs) and bone mineral density (BMD) in black and non-black participants were evaluated at 48 weeks. Wilcoxon signed-rank tests and Wilcoxon rank sum tests assessed within and between-race differences. Results Of 165 participants enrolled, 129 (40 black and 89 non-black) had complete data. At baseline, black participants had lower total 25-(OH)D [median (Q1,Q3) 22.6 (15.8, 26.9) vs. 31.1 (23.1, 38.8) ng/ml, p<0.001] but higher bioavailable 25-(OH)D [2.9 (1.5, 5.2) vs. 2.0 (1.5, 3.0) ng/ml, p=0.022] than non-black participants. After 48 weeks of VitD/Ca supplementation, bioavailable 25-(OH)D increased more in black than non-black participants, but there were no between-race differences in change in BTMs or BMD. The associations between increases in 25-(OH)D levels and change in bone outcomes appeared similar for both total and bioavailable 25-(OH)D. Conclusions Baseline and change in bioavailable 25-(OH)D were higher among black adults initiating ART with VitD/Ca; however, associations between 25-(OH)D and bone outcomes appeared similar for total and bioavailable 25-(OH)D. The assessment of total 25-(OH)D may be sufficient for evaluation of vitamin D status in black HIV-infected individuals.

Continued Interest and Controversy: Vitamin D in HIV

“…In both arms, DBP increased from baseline, but total 25OHD and bioavailable 25OHD increased only in the supplementation group [56]. PTH levels increased significantly in the placebo group but not the supplementation group, supporting the concept of a functional VitD deficiency; however, BMD changes were not consistently associated with bioavailable VitD [101]. In a small study of patients on TDF-FTC-EFV switched to darunavir(DRV)/r, a significant increase in BMD and 25OHD levels were observed compared with those continuing TDF-FTC-EFV, but no significant change was observed in DBP, PTH, or renal function [102].…”

Tenofovir disoproxil fumarate appears to disrupt the relationship of vitamin D and parathyroid hormone

“…Although PTH increases in response to small changes in serum calcium [10], detecting such a change would be unlikely, given the tight regulation of circulating calcium, which was not different across groups. While other studies have shown that TDF raises PTH [6,7,14], the TDF-associated PTH increase does not appear to be mediated by increased urinary calcium excretion [5,6]. Although hyperphosphatemia increases PTH [10], this would not pertain here, since TDF causes renal phosphate loss [5].…”

“…Although hyperphosphatemia increases PTH [10], this would not pertain here, since TDF causes renal phosphate loss [5]. Increased vitamin D binding protein, found at TDF-containing cART initiation [7,14], and with higher plasma tenofovir concentrations [5], may decrease free 25-OHD and lead to 'functional' vitamin D deficiency. Our findings differ from those of a previous study examining the relationship of TDF with 25-OHD and PTH in participants with mean (sd) age 47 (9.8) years, who were 94% White [15].…”

Vitamin D does not Modulate Immune-Mediated Bone loss during ART Initiation

“…ACTG A5280 (NCT01403051) was a 48-week, randomized, double-blind, placebo-controlled study in which 165 PWH, naive to ART, with 25-(OH)D level ≥10 and <75 ng/ml (≥25 and <188 nmol/l), creatinine clearance (CrCl) ≥60 ml/min by Cockcroft-Gault, and serum calcium <10.5 mg/dl, were randomized to receive 4,000 IU cholecalciferol (vitamin D3) daily plus 500 mg calcium carbonate twice daily or identically matching placebos (Tishcon Corporation, Westbury, NY, USA). Primary and secondary treatment outcomes of percentage change in total hip and lumbar spine BMD, and bone turnover markers, procollagen-1 N-terminal pep-tide (P1NP) and C-terminal telopeptide of type 1 collagen (CTX), inflammatory biomarkers (IL-6, sTNFr-I, sTNFr-II and sCD14) and bioavailable VitD from baseline to 48 weeks have been previously reported [5,10].…”