title: 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: BACKGROUND
  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.
  
  
  METHODS
  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 D(2) im. Blood samples were obtained at baseline and 1, 2, and 3 months after treatment.
  
  
  METHODS
  Changes in 1,25(OH)(2)-vitamin D and FGF-23 were measured.
  
  
  RESULTS
  Loading dose of vitamin D(2) increased 1,25(OH)(2)-vitamin D(2) 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.
authors.affiliation: Wellchild Laboratory, The Evelina Children’s Hospital, London, SE1 7EH, United Kingdom.
authors.forename: C
authors.initials: C
authors.lastname: Turner
authors.forename: N
authors.initials: N
authors.lastname: Dalton
authors.forename: R
authors.initials: R
authors.lastname: Inaoui
authors.forename: I
authors.initials: I
authors.lastname: Fogelman
authors.forename: W D
authors.initials: WD
authors.lastname: Fraser
authors.forename: G
authors.initials: G
authors.lastname: Hampson
mesh_terms: D000368:Aged; D019386:Alendronate / Q000627:therapeutic use; D015519:Bone Density; D050071:Bone Density Conservation Agents / Q000627:therapeutic use; D004872:Ergocalciferols / Q000494:pharmacology*; D005260:Female; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000097:blood*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010024:Osteoporosis / Q000097:blood; D017698:Postmenopause / Q000097:blood; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000097:blood; D014808:Vitamin D Deficiency / Q000097:blood* / Q000188:drug therapy
chemical_list: D050071:Bone Density Conservation Agents; D004872:Ergocalciferols; C000717427:FGF23 protein, human; D014807:Vitamin D; D005346:Fibroblast Growth Factors; C097949:1,25-dihydroxyvitamin D; D000089703:Fibroblast Growth Factor-23; D019386:Alendronate