title: Circulating levels of soluble klotho and FGF23 in X-linked hypophosphatemia: circadian variance, effects of treatment, and relationship to parathyroid status.
abstract: BACKGROUND
  Circulating fibroblast growth factor (FGF)-23 is variably elevated in individuals with X-linked hypophosphatemia (XLH), and klotho has recently been shown to effect renal phosphate handling, yet limited data are available on circulating FGF23 and klotho in XLH.
  
  
  OBJECTIVE
  The objective of the study was to characterize circulating FGF23 and klotho in XLH.
  
  
  METHODS
  Children and adults with XLH withheld medication for 14 d. Fasting serum FGF23, PTH, klotho, phosphate, and 1,25 dihydroxyvitamin D were obtained. Treated adults were also sampled, and circadian sampling was performed in selected individuals.
  
  
  METHODS
  The study was conducted at a hospital research unit at an academic medical center.
  
  
  METHODS
  Participants included 23 individuals with XLH and eight controls.
  
  
  METHODS
  There were no interventions.
  
  
  METHODS
  Serum klotho and FGF23 were measured.
  
  
  RESULTS
  FGF23 was greater in XLH than in controls and greater in treated XLH subjects compared with XLH subjects not receiving medical therapy. Children had higher klotho levels than adults, but values in XLH were similar to controls. A strong positive correlation between FGF23 and PTH was found in XLH subjects, whereas there was no relationship between these variables in controls. Circulating klotho, but not FGF23, has a diurnal pattern.
  
  
  CONCLUSIONS
  Serum klotho declines with age and demonstrates circadian variation but is normal in XLH. Serum FGF23 is similar in children and adults, is elevated in XLH, further increases with therapy, and demonstrates no diurnal variation. The direct relationship between FGF23 and PTH in subjects with XLH suggests that FGF23 regulation of PTH secretion is aberrant in this disorder.
authors.affiliation: Department of Pediatrics, Yale University School of Medicine, New Haven, Connecticut 06520-8064, USA. thomas.carpenter@yale.edu
authors.forename: Thomas O
authors.initials: TO
authors.lastname: Carpenter
authors.forename: Karl L
authors.initials: KL
authors.lastname: Insogna
authors.forename: Jane H
authors.initials: JH
authors.lastname: Zhang
authors.forename: Bruce
authors.initials: B
authors.lastname: Ellis
authors.forename: Sherril
authors.initials: S
authors.lastname: Nieman
authors.forename: Christine
authors.initials: C
authors.lastname: Simpson
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Olear
authors.forename: Caren M
authors.initials: CM
authors.lastname: Gundberg
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D050071:Bone Density Conservation Agents / Q000627:therapeutic use; D002117:Calcitriol / Q000627:therapeutic use; D002648:Child; D002940:Circadian Rhythm / Q000502:physiology*; D004797:Enzyme-Linked Immunosorbent Assay; D053098:Familial Hypophosphatemic Rickets / Q000097:blood* / Q000188:drug therapy*; D005260:Female; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000097:blood*; D040181:Genetic Diseases, X-Linked; D005966:Glucuronidase / Q000097:blood*; D006801:Humans; D000090265:Klotho Proteins; D008297:Male; D008875:Middle Aged; D010281:Parathyroid Hormone / Q000097:blood*; D010710:Phosphates / Q000097:blood / Q000627:therapeutic use; D014807:Vitamin D / Q000031:analogs & derivatives / Q000097:blood
chemical_list: D050071:Bone Density Conservation Agents; C000717427:FGF23 protein, human; D010281:Parathyroid Hormone; D010710:Phosphates; D014807:Vitamin D; D005346:Fibroblast Growth Factors; C097949:1,25-dihydroxyvitamin D; D000089703:Fibroblast Growth Factor-23; D005966:Glucuronidase; D000090265:Klotho Proteins; D002117:Calcitriol