OBJECTIVES: 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. CONCLUSION: 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.

Centre de Référence des Maladies Rénales Rares Hôpital Femme Mère Enfant Hospices Civils de Lyon Bron France

Clinic of Pediatric Nephrology Charite Children's Hospital Berlin Germany

Department of Pediatric Kidney Liver and Metabolic Diseases Hannover Medical School Hannover Germany

Department of Pediatric Kidney Liver and Metabolic Diseases Hannover Medical School Hannover Germany; Integrated Research and Treatment Center Transplantation Hannover Medical School Hannover Germany

Department of Pediatric Nephrology Sisli Educational and Research Hospital Istanbul Turkey

Department of Pediatric Nephrology University of Gaziantep Gaziantep Turkey

Department of Pediatrics University Hospital Rostock Rostock Germany

Department of Psychology University of Copenhagen Copenhagen Denmark

Dialysis and Transplantation Department of Pediatrics Padova Italy

Diskapi Children's Hospital Ankara Turkey

Division of Pediatric Nephrology Center for Pediatrics and Adolescent Medicine Heidelberg Germany

Division of Pediatric Nephrology Cukurova University School of Medicine Adana Turkey

Division of Pediatric Nephrology Dpt of Pediatrics Hacettepe University Faculty of Medicine Ankara Turkey

Division of Pediatric Nephrology Ege University Medical Faculty Izmir Turkey

Division of Pediatric Nephrology Great Ormond Street Hospital London United Kingdom

Division of Pediatric Nephrology Istanbul Medeniyet University Göztepe Training and Research Hospital Istanbul Turkey

Division of Pediatric Nephrology Istanbul University Cerrahpasa Faculty of Medicine Istanbul Turkey

Division of Pediatric Nephrology Uludag University Faculty of Medicine Bursa Turkey

Division of Pediatric Nephrology University Children's Hospital Essen Germany

KfH Kidney Center for Children Marburg Germany

Pediatric Hospital University Hospital Motol Prague Czech Republic

University Children's Hospital Hamburg Germany

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