title: Activation of FGF-23 mediated vitamin D degradative pathways by cholecalciferol.
abstract: BACKGROUND
  The optimal circulating concentration of 25(OH) vitamin D is controversial.
  
  
  OBJECTIVE
  The aim was to investigate if FGF-23 and 24,25(OH)2D can guide cholecalciferol replacement.
  
  
  METHODS
  Oral cholecalciferol (10,000 IU weekly) administered to subjects with 25(OH)D levels < 20 ηg/mL and eGFR > 60 mL/min/1.73 m(2) (n = 25), chronic kidney disease (CKD) (n = 27), or end stage renal disease (ESRD) (n = 14).
  
  
  METHODS
  The study was conducted at the Veterans Affairs clinics.
  
  
  METHODS
  Serum FGF-23, PTH, 25(OH)D, 1,25(OH)2D, 24,25(OH)2D, calcium, and phosphorous concentrations, and urinary excretion of calcium and phosphorus at baseline and after 8 weeks of treatment.
  
  
  RESULTS
  Cholecalciferol treatment increased concentrations of serum 25(OH)D by (19.3 ± 8 ηg/mL, P = .001; 12.2 ± 9 ηg/mL, P = .0001) and 24,25(OH)2D (1.14 ± 0.89 ηg/mL, P = .0024; 1.0 ± 0.72 ηg/mL P = .0002), and reduced serum PTH (-11 ± 21 pg/mL, P = .0292; -42 ± 68 pg/mL, P = .0494) in normal and CKD subjects, respectively. Cholecalciferol increased serum FGF-23 levels only in normal subjects (44 ± 57 ηg/mL, P = .01). Increments in serum 25(OH)D positively correlated with serum FGF-23 and 24,25(OH)2D and negatively correlated with PTH. In ESRD, cholecalciferol administration increased 25(OH)D by (16.6 ± 6.6 ηg/mL P ≤ .05) without changing 24,25(OH)2D, FGF-23 or PTH levels.
  
  
  CONCLUSIONS
  Modest elevations of serum 25(OH)D levels after cholecalciferol treatment are sufficient to induce compensatory degradative pathways in patients with sufficient renal reserves, suggesting that optimal circulating 25(OH)D levels are approximately 20 ηg/mL. In addition, catabolism of 25(OH)D may also contribute to the low circulating vitamin D levels in CKD, since elevations of FGF-23 in CKD are associated with increased 24,25(OH)2D after cholecalciferol administration.
authors: University of Tennessee Health Science Center (A.S., B.M.W., L.D.Q.), Memphis, Tennessee 38103; Veterans Affairs Medical Center (B.M.W., G.G.G.), Memphis, Tennessee 38103; Marshall University (H.A.), Huntington, West Virginia 25701; and University of Miami (V.D.), Miami, Florida 33136.
authors: Hala
authors: H
authors: Alshayeb
authors: Arif
authors: A
authors: Showkat
authors: Barry M
authors: BM
authors: Wall
authors: Geeta G
authors: GG
authors: Gyamlani
authors: Valentin
authors: V
authors: David
authors: L Darryl
authors: LD
authors: Quarles
mesh_terms: D015650:24,25-Dihydroxyvitamin D 3 / Q000097:blood* / Q000652:urine; D000368:Aged; D002762:Cholecalciferol / Q000008:administration & dosage* / Q000378:metabolism; D016903:Drug Monitoring / Q000379:methods*; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000097:blood*; D006801:Humans; D007668:Kidney / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D010281:Parathyroid Hormone / Q000097:blood; D011446:Prospective Studies; D051436:Renal Insufficiency, Chronic / Q000378:metabolism; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000097:blood / Q000652:urine; D014808:Vitamin D Deficiency / Q000097:blood / Q000188:drug therapy*; D014815:Vitamins / Q000008:administration & dosage / Q000378:metabolism
chemical_list: C000717427:FGF23 protein, human; D010281:Parathyroid Hormone; D014815:Vitamins; D014807:Vitamin D; D002762:Cholecalciferol; D015650:24,25-Dihydroxyvitamin D 3; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23; C104450:25-hydroxyvitamin D