Markers of bone metabolism are affected by renal function and growth hormone therapy in children with chronic kidney disease

Anke Doyon; Dagmar Christiane Fischer; Aysun Karabay Bayazit; Nur Canpolat; Ali Duzova; Betül Sözeri; Justine Bacchetta; Ayse Balat; Anja Büscher; Cengiz Candan; Nilgun Cakar; Osman Donmez; Jiri Dusek; Martina Heckel; Günter Klaus; Sevgi Mir; Gül Özcelik; Lale Sever; Rukshana Shroff; Enrico Vidal; Elke Wühl; Matthias Gondan; Anette Melk; Uwe Querfeld; Dieter Haffner; Franz Schaefer

doi:10.1371/journal.pone.0113482

Markers of bone metabolism are affected by renal function and growth hormone therapy in children with chronic kidney disease

Anke Doyon^*, Dagmar Christiane Fischer, Aysun Karabay Bayazit, Nur Canpolat, Ali Duzova, Betül Sözeri, Justine Bacchetta, Ayse Balat, Anja Büscher, Cengiz Candan, Nilgun Cakar, Osman Donmez, Jiri Dusek, Martina Heckel, Günter Klaus, Sevgi Mir, Gül Özcelik, Lale Sever, Rukshana Shroff, Enrico VidalElke Wühl, Matthias Gondan, Anette Melk, Uwe Querfeld, Dieter Haffner, Franz Schaefer

^*Corresponding author for this work

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Abstract

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/ 1.73m². 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.

Original language	English
Article number	e0113482
Journal	PLoS ONE
Volume	10
Issue number	2
ISSN	1932-6203
DOIs	https://doi.org/10.1371/journal.pone.0113482
Publication status	Published - 6 Feb 2015

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Doyon, A., Fischer, D. C., Bayazit, A. K., Canpolat, N., Duzova, A., Sözeri, B., Bacchetta, J., Balat, A., Büscher, A., Candan, C., Cakar, N., Donmez, O., Dusek, J., Heckel, M., Klaus, G., Mir, S., Özcelik, G., Sever, L., Shroff, R., ... Schaefer, F. (2015). Markers of bone metabolism are affected by renal function and growth hormone therapy in children with chronic kidney disease. PLoS ONE, 10(2), [e0113482]. https://doi.org/10.1371/journal.pone.0113482

Doyon, A, Fischer, DC, Bayazit, AK, Canpolat, N, Duzova, A, Sözeri, B, Bacchetta, J, Balat, A, Büscher, A, Candan, C, Cakar, N, Donmez, O, Dusek, J, Heckel, M, Klaus, G, Mir, S, Özcelik, G, Sever, L, Shroff, R, Vidal, E, Wühl, E, Gondan, M, Melk, A, Querfeld, U, Haffner, D & Schaefer, F 2015, 'Markers of bone metabolism are affected by renal function and growth hormone therapy in children with chronic kidney disease', PLoS ONE, vol. 10, no. 2, e0113482. https://doi.org/10.1371/journal.pone.0113482

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title = "Markers of bone metabolism are affected by renal function and growth hormone therapy in children with chronic kidney disease",

abstract = "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/ 1.73m2. 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.",

author = "Anke Doyon and Fischer, {Dagmar Christiane} and Bayazit, {Aysun Karabay} and Nur Canpolat and Ali Duzova and Bet{\"u}l S{\"o}zeri and Justine Bacchetta and Ayse Balat and Anja B{\"u}scher and Cengiz Candan and Nilgun Cakar and Osman Donmez and Jiri Dusek and Martina Heckel and G{\"u}nter Klaus and Sevgi Mir and G{\"u}l {\"O}zcelik and Lale Sever and Rukshana Shroff and Enrico Vidal and Elke W{\"u}hl and Matthias Gondan and Anette Melk and Uwe Querfeld and Dieter Haffner and Franz Schaefer",

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doi = "10.1371/journal.pone.0113482",

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TY - JOUR

T1 - Markers of bone metabolism are affected by renal function and growth hormone therapy in children with chronic kidney disease

AU - Doyon, Anke

AU - Fischer, Dagmar Christiane

AU - Bayazit, Aysun Karabay

AU - Canpolat, Nur

AU - Duzova, Ali

AU - Sözeri, Betül

AU - Bacchetta, Justine

AU - Balat, Ayse

AU - Büscher, Anja

AU - Candan, Cengiz

AU - Cakar, Nilgun

AU - Donmez, Osman

AU - Dusek, Jiri

AU - Heckel, Martina

AU - Klaus, Günter

AU - Mir, Sevgi

AU - Özcelik, Gül

AU - Sever, Lale

AU - Shroff, Rukshana

AU - Vidal, Enrico

AU - Wühl, Elke

AU - Gondan, Matthias

AU - Melk, Anette

AU - Querfeld, Uwe

AU - Haffner, Dieter

AU - Schaefer, Franz

PY - 2015/2/6

Y1 - 2015/2/6

N2 - 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/ 1.73m2. 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.

AB - 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/ 1.73m2. 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.

U2 - 10.1371/journal.pone.0113482

DO - 10.1371/journal.pone.0113482

M3 - Journal article

C2 - 25659076

AN - SCOPUS:84922594386

SN - 1932-6203

VL - 10

JO - PLoS Computational Biology

JF - PLoS Computational Biology

IS - 2

M1 - e0113482

ER -

Markers of bone metabolism are affected by renal function and growth hormone therapy in children with chronic kidney disease

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