Calculated free and bioavailable vitamin D metabolite concentrations in vitamin D-deficient hip fracture patients after supplementation with cholecalciferol and ergocalciferol

We previously showed that oral cholecalciferol and ergocalciferol have comparable effects in decreasing circulating parathyroid hormone (PTH), despite a greater increase in total serum 25-hydroxyvitamin D (25OHD) concentration with cholecalciferol supplementation. However, the effects of cholecalciferol and ergocalciferol on total serum 1,25-dihydroxyvitamin D (1,25 (OH)(2)D), vitamin D-binding protein (DBP), free 25OHD and free 1,25(OH)(2)D concentrations have not been previously studied. We randomized 95 hip fracture patients (aged 83 8 years) with vitamin D deficiency (serum 25OHD <50 nmol/L) to oral supplementation with either cholecalciferol 1000 IU/day (n = 47) or ergocalciferol 1000 IU/day (n = 48) for three months. All were given matching placebos of the alternative treatment to maintain blinding. We measured serum 25OHD (high-pressure liquid chromatography), 1,25(OH)2D (Diasorin radioimmunoassay), DBP (immunonephelometry), ionized calcium (Bayer 800 ion-selective electrode) and albumin (bromocresol green) concentrations before and after treatment. We calculated free and bioavailable concentrations of the vitamin D metabolites using albumin and DBP, and calculated free vitamin D metabolite indices as the ratios between the molar concentrations of the vitamin D metabolites and DBP. Seventy participants (74%) completed the study with paired samples for analysis. Total serum 1,25(OH)2D did not change significantly with either treatment (p > 0.05, post-treatment vs baseline). Both treatments were associated with comparable increases in DBP (cholecalciferol: + 18%, ergocalciferol: +16%, p = 0.32 between groups), albumin (cholecalciferol: +31%, ergocalciferol: +21%, p = 0.29 between groups) and calculated free 25OHD (cholecalciferol: +46%, ergocalciferol: +36%, p = 0.08), with comparable decreases in free 1,25(OH)2D (cholecalciferol: -17%, ergocalciferol: -19%, p = 032 between groups). In the treatment-adherent subgroup the increase in ionized calcium was marginally greater with cholecalciferol compared with ergocalciferol (cholecalciferol: +8%, ergocalciferol: +5%, p = 0.03 between groups). There were no significant differences between the treatments in their effects on the calculated bioavailable concentrations or free indices of the vitamin D metabolites (p > 0.05 between groups). In vitamin D-deficient hip fracture patients, oral supplementation with cholecalciferol and ergocalciferol had no effect on total serum 1,25(OH)(2)D, and comparable effects on DBP and free vitamin D metabolite concentrations. This is despite cholecalciferol having greater effects than ergocalciferol in increasing total 25OHD, and in increasing ionized calcium in treatment-adherent subjects. These findings may explain why cholecalciferol and ergocalciferol supplementation result in similar magnitudes of PTH reduction, but implicate potential differences in other vitamin D metabolites, such as 24,25(OH)(2)D, that could explain their different effects on ionized calcium. (C) 2013 Elsevier Inc. All rights reserved.