Markers of Bone Metabolism Are Affected by Renal Function and Growth Hormone Therapy in Children with Chronic Kidney Disease

Abstract

ObjectivesThe 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.MethodsBone 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.ResultsStandardized 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.ConclusionMarkers 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.

Management of bone disease in cystinosis: Statement from an international conference

“…New biomarkers may better reflect bone cell activity in CMBD, and pediatric reference values are available . Bone ALP, an osteoblast enzyme, is a sensitive and specific marker of bone formation and remodeling during periods of rapid longitudinal growth and in cases of rickets . TRAP5b is considered a specific marker of late osteoclast differentiation, and sclerostin is an osteocyte‐derived inhibitor of bone formation .…”

“…Measurement of serum PTH, calcium, 25(OH) vitamin D, and phosphate also serve as the mainstays of monitoring for CKD-MBD. 38 Nevertheless, infants and adolescents with cystinosis may develop bone disease despite largely "normal" blood levels of phosphate, calcium and ALP; normal blood levels have a wide standard range and daily fluctuations, are not always biochemically evident, and may have a large cumulative effect upon bone metabolism. Therefore, urine losses for calcium and phosphate should be monitored as well.…”

“…40 Bone ALP, an osteoblast enzyme, is a sensitive and specific marker of bone formation and remodeling during periods of rapid longitudinal growth and in cases of rickets. 24,38 TRAP5b is considered a specific marker of late osteoclast differentiation, 38 and sclerostin is an osteocyte-derived inhibitor of bone formation. 38,41,42 Fibroblast growth factor 23 (FGF23), released by osteocytes and osteoblasts, helps maintain mineral and vitamin D homeostasis, and is the earliest detectable abnormality in bone mineral metabolism in CKD patients.…”

“…24,38 TRAP5b is considered a specific marker of late osteoclast differentiation, 38 and sclerostin is an osteocyte-derived inhibitor of bone formation. 38,41,42 Fibroblast growth factor 23 (FGF23), released by osteocytes and osteoblasts, helps maintain mineral and vitamin D homeostasis, and is the earliest detectable abnormality in bone mineral metabolism in CKD patients. 38,43 However, FGF23 levels are typically normal in patients with cystinosis prior to dialysis, possibly due to hypophosphatemia.…”

Is arterial calcification in children and adolescents with end‐stage renal disease a rare finding?

“…In children, an independent association between IMT in the carotid artery and (i) calcium and phosphorus product and (ii) the cumulative dose of calcium base phosphorus chelators was reported . In another recent multi‐centre based study, systolic blood pressure (SBP) was independently associated with IMT of the carotid artery …”