title: FGF-23 serum levels and bone histomorphometric results in adult patients with chronic kidney disease on dialysis.
abstract: BACKGROUND
  Fibroblast growth factor-23 (FGF-23) is a hormone principally produced by osteocytes/osteoblasts. In patients with chronic kidney disease (CKD), FGF-23 levels are usually elevated and can reach up to 300 - 400 times the normal range. FGF-23 is regulated by local bone-related and systemic factors, but the relationship between circulating FGF-23 concentrations and bone remodeling and mineralization in CKD has not been well characterized. In the current study, we examined the relationship between FGF-23 levels and bone histomorphometry parameters in adult patients with renal osteodystrophy.
  
  
  METHODS
  36 patients on dialysis (CKD-5D) underwent bone biopsies after tetracycline double labeling. Blood drawings were done at time of biopsy to determine serum levels of markers of bone and mineral metabolism.
  
  
  RESULTS
  Patients with high bone turnover had higher values of serum FGF-23 than patients with low bone turnover. FGF-23 levels correlated with activation frequency (ρ = 0.60, p < 0.01) and bone formation rate (ρ = 0.57, p < 0.01). Normal mineralization was observed in 90% of patients with FGF-23 levels above 2,000 pg/mL. Furthermore, FGF-23 correlated negatively with mineralization lag time (ρ = -0.69, p < 0.01) and osteoid maturation time (ρ = -0.46, p < 0.05) but not with osteoid thickness (ρ = 0.08, ns). Regression analysis showed that FGF-23 was the only independent predictor of mineralization lag time. FGF-23 correlated with cancellous bone volume (ρ = 0.38, p < 0.05) but did not predict it.
  
  
  CONCLUSIONS
  Circulating FGF-23 concentrations may reflect alterations in ongoing bone formation along with active mineralization, but not exclusively in bone formation or mineralization. Abnormal mineralization lag time (> 100 days) was mainly seen in patients with FGF-23 levels less than 2,000 pg/mL, while very high levels of FGF-23 are associated with normal mineralization lag time.
authors.forename: Florence
authors.initials: F
authors.lastname: Lima
authors.forename: Amr
authors.initials: A
authors.lastname: El-Husseini
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: Monier-Faugere
authors.forename: Valentin
authors.initials: V
authors.lastname: David
authors.forename: Hanna
authors.initials: H
authors.lastname: Mawad
authors.forename: Darryl
authors.initials: D
authors.lastname: Quarles
authors.forename: Hartmut H
authors.initials: HH
authors.lastname: Malluche
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D016723:Bone Remodeling / Q000502:physiology*; D012080:Chronic Kidney Disease-Mineral and Bone Disorder / Q000097:blood* / Q000473:pathology / Q000628:therapy; D003430:Cross-Sectional Studies; D005260:Female; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000097:blood*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010012:Osteogenesis / Q000502:physiology; D006435:Renal Dialysis; D051436:Renal Insufficiency, Chronic / Q000097:blood* / Q000473:pathology* / Q000628:therapy
chemical_list: D015415:Biomarkers; C000717427:FGF23 protein, human; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23