title: Calculated free and bioavailable vitamin D metabolite concentrations in vitamin D-deficient hip fracture patients after supplementation with cholecalciferol and ergocalciferol.
abstract: 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)2D), vitamin D-binding protein (DBP), free 25OHD and free 1,25(OH)2D 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=0.32 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)2D, 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)2D, that could explain their different effects on ionized calcium.
authors.affiliation: Department of Core Clinical Pathology and Biochemistry, Royal Perth Hospital, Perth, Western Australia, Australia. Paul.Glendenning@health.wa.gov.au
authors.forename: Paul
authors.initials: P
authors.lastname: Glendenning
authors.forename: Gerard T
authors.initials: GT
authors.lastname: Chew
authors.forename: Charles A
authors.initials: CA
authors.lastname: Inderjeeth
authors.forename: Mario
authors.initials: M
authors.lastname: Taranto
authors.forename: William D
authors.initials: WD
authors.lastname: Fraser
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002762:Cholecalciferol / Q000627:therapeutic use*; D004872:Ergocalciferols / Q000627:therapeutic use*; D005260:Female; D006620:Hip Fractures / Q000188:drug therapy* / Q000378:metabolism*; D006801:Humans; D008297:Male; D014807:Vitamin D / Q000378:metabolism*; D014808:Vitamin D Deficiency / Q000188:drug therapy* / Q000378:metabolism*
chemical_list: D004872:Ergocalciferols; D014807:Vitamin D; D002762:Cholecalciferol
keywords: Calculated free vitamin D concentrations; Cholecalciferol; Ergocalciferol; Hip fracture; Vitamin D-binding protein