Effect of a 300 000-IU loading dose of ergocalciferol (vitamin D2) on circulating 1,25(OH)2-vitamin D and fibroblast growth factor-23 (FGF-23) in vitamin D insufficiency

Abstract

Context: Several trials have reported an increased risk of fractures and falls after intermittent high-dose vitamin D. Treatment with loading doses of vitamin D may increase 1,25(OH)2 vitamin D catabolism through changes in calcium/phosphate homeostasis and fibroblast growth factor-23 (FGF-23). Objective: The aim was to determine the effects of high-dose vitamin D on circulating concentrations of 1,25(OH)2 vitamin D and FGF-23 in patients with osteoporosis and vitamin D insufficiency. Design, Setting, Patients, and Intervention: We carried out a prospective study of 45 subjects with vitamin D deficiency/insufficiency treated with a bolus dose of 300 000 IU of vitamin D2 im. Blood samples were obtained at baseline and 1, 2, and 3 months after treatment. Outcome Measures: Changes in 1,25(OH)2-vitamin D and FGF-23 were measured. Results: Loading dose of vitamin D2 increased 1,25(OH)2-vitamin D2 at 3 months, with a mean [SD] of 41 [56] pmol/L at baseline and 162.3 [137.8] pmol/L at 3 months (P < .001). FGF-23 increased significantly at all time points with a peak at 3 months, with percent change from baseline (mean [SEM]) of 50% [48%] at 3 months (P < .01). There was a positive correlation between FGF-23 and serum phosphate (r = 0.36, P = .024) and calcium (r = 0.532, P < .001) and a negative correlation between total 1,25(OH)2-vitamin D and FGF-23 (r = -0.32, P = .036) at 3 months. Conclusions: High-dose vitamin D increases 1,25(OH)2-vitamin D and FGF-23 concentration. Further studies are required to determine whether adjusting vitamin D dose and frequency to minimize increases in FGF-23 may prevent the adverse outcomes associated with high-dose intermittent vitamin D supplementation. Copyright © 2013 by The Endocrine Society.