title: Markers of bone metabolism are affected by renal function and growth hormone therapy in children with chronic kidney disease.
abstract: OBJECTIVE
  The extent and relevance of altered bone metabolism for statural growth in children with chronic kidney disease is controversial. We analyzed the impact of renal dysfunction and recombinant growth hormone therapy on a panel of serum markers of bone metabolism in a large pediatric chronic kidney disease cohort.
  
  
  METHODS
  Bone alkaline phosphatase (BAP), tartrate-resistant acid phosphatase 5b (TRAP5b), sclerostin and C-terminal FGF-23 (cFGF23) normalized for age and sex were analyzed in 556 children aged 6-18 years with an estimated glomerular filtration rate (eGFR) of 10-60 ml/min/1.73 m2. 41 children receiving recombinant growth hormone therapy were compared to an untreated matched control group.
  
  
  RESULTS
  Standardized levels of BAP, TRAP5b and cFGF-23 were increased whereas sclerostin was reduced. BAP was correlated positively and cFGF-23 inversely with eGFR. Intact serum parathormone was an independent positive predictor of BAP and TRAP5b and negatively associated with sclerostin. BAP and TRAP5B were negatively affected by increased C-reactive protein levels. In children receiving recombinant growth hormone, BAP was higher and TRAP5b lower than in untreated controls. Sclerostin levels were in the normal range and higher than in untreated controls. Serum sclerostin and cFGF-23 independently predicted height standard deviation score, and BAP and TRAP5b the prospective change in height standard deviation score.
  
  
  CONCLUSIONS
  Markers of bone metabolism indicate a high-bone turnover state in children with chronic kidney disease. Growth hormone induces an osteoanabolic pattern and normalizes osteocyte activity. The osteocyte markers cFGF23 and sclerostin are associated with standardized height, and the markers of bone turnover predict height velocity.
authors: Division of Pediatric Nephrology, Center for Pediatrics and Adolescent Medicine, Heidelberg, Germany.
authors: Anke
authors: A
authors: Doyon
authors: Department of Pediatrics, University Hospital Rostock, Rostock, Germany.
authors: Dagmar-Christiane
authors: DC
authors: Fischer
authors: Division of Pediatric Nephrology, Cukurova University, School of Medicine, Adana, Turkey.
authors: Aysun Karabay
authors: AK
authors: Bayazit
authors: Division of Pediatric Nephrology, Istanbul University Cerrahpasa Faculty of Medicine, Istanbul, Turkey.
authors: Nur
authors: N
authors: Canpolat
authors: Division of Pediatric Nephrology, Dpt. of Pediatrics, Hacettepe University Faculty of Medicine, Ankara, Turkey.
authors: Ali
authors: A
authors: Duzova
authors: Division of Pediatric Nephrology, Ege University Medical Faculty, Izmir, Turkey.
authors: Betül
authors: B
authors: Sözeri
authors: Centre de Référence des Maladies Rénales Rares, Hôpital Femme Mère Enfant, Hospices Civils de Lyon, Bron, France.
authors: Justine
authors: J
authors: Bacchetta
authors: Department of Pediatric Nephrology, University of Gaziantep, Gaziantep, Turkey.
authors: Ayse
authors: A
authors: Balat
authors: Division of Pediatric Nephrology, University Children's Hospital, Essen, Germany.
authors: Anja
authors: A
authors: Büscher
authors: Division of Pediatric Nephrology, Istanbul Medeniyet University, Göztepe Training and Research Hospital, Istanbul, Turkey.
authors: Cengiz
authors: C
authors: Candan
authors: Diskapi Children's Hospital, Ankara, Turkey.
authors: Nilgun
authors: N
authors: Cakar
authors: Division of Pediatric Nephrology, Uludag University Faculty of Medicine, Bursa, Turkey.
authors: Osman
authors: O
authors: Donmez
authors: Pediatric Hospital, University Hospital Motol, Prague, Czech Republic.
authors: Jiri
authors: J
authors: Dusek
authors: University Children's Hospital, Hamburg, Germany.
authors: Martina
authors: M
authors: Heckel
authors: KfH Kidney Center for Children, Marburg, Germany.
authors: Günter
authors: G
authors: Klaus
authors: Division of Pediatric Nephrology, Ege University Medical Faculty, Izmir, Turkey.
authors: Sevgi
authors: S
authors: Mir
authors: Department of Pediatric Nephrology, Sisli Educational and Research Hospital, Istanbul, Turkey.
authors: Gül
authors: G
authors: Özcelik
authors: Division of Pediatric Nephrology, Istanbul University Cerrahpasa Faculty of Medicine, Istanbul, Turkey.
authors: Lale
authors: L
authors: Sever
authors: Division of Pediatric Nephrology, Great Ormond Street Hospital, London, United Kingdom.
authors: Rukshana
authors: R
authors: Shroff
authors: Dialysis and Transplantation Department of Pediatrics, Padova, Italy.
authors: Enrico
authors: E
authors: Vidal
authors: Division of Pediatric Nephrology, Center for Pediatrics and Adolescent Medicine, Heidelberg, Germany.
authors: Elke
authors: E
authors: Wühl
authors: Department of Psychology, University of Copenhagen, Copenhagen, Denmark.
authors: Matthias
authors: M
authors: Gondan
authors: Department of Pediatric Kidney, Liver and Metabolic Diseases, Hannover Medical School, Hannover, Germany; Integrated Research and Treatment Center Transplantation (IFB-Tx), Hannover Medical School, Hannover, Germany.
authors: Anette
authors: A
authors: Melk
authors: Clinic of Pediatric Nephrology, Charite Children's Hospital, Berlin, Germany.
authors: Uwe
authors: U
authors: Querfeld
authors: Department of Pediatric Kidney, Liver and Metabolic Diseases, Hannover Medical School, Hannover, Germany.
authors: Dieter
authors: D
authors: Haffner
authors: Division of Pediatric Nephrology, Center for Pediatrics and Adolescent Medicine, Heidelberg, Germany.
authors: Franz
authors: F
authors: Schaefer
mesh_terms: D000135:Acid Phosphatase / Q000097:blood*; D048868:Adaptor Proteins, Signal Transducing; D000293:Adolescent; D000469:Alkaline Phosphatase / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D019485:Bone Morphogenetic Proteins / Q000097:blood*; D001842:Bone and Bones / Q000378:metabolism*; D002648:Child; D005260:Female; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000097:blood*; D005819:Genetic Markers; D019382:Human Growth Hormone / Q000008:administration & dosage*; D006801:Humans; D007527:Isoenzymes / Q000097:blood*; D007677:Kidney Function Tests; D008297:Male; D051436:Renal Insufficiency, Chronic / Q000097:blood / Q000503:physiopathology; D000071681:Tartrate-Resistant Acid Phosphatase
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D015415:Biomarkers; D019485:Bone Morphogenetic Proteins; C000717427:FGF23 protein, human; D005819:Genetic Markers; D007527:Isoenzymes; C422903:SOST protein, human; D019382:Human Growth Hormone; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23; D000469:Alkaline Phosphatase; D000135:Acid Phosphatase; D000071681:Tartrate-Resistant Acid Phosphatase