Effect of therapy with recombinant human growth hormone on insulin-like growth factor system components and serum levels of biochemical markers of bone formation in children after severe burn injury

Gordon L. Klein, Steven E. Wolf, Craig B. Langman, Clifford J. Rosen, Subburaman Mohan, Bruce S. Keenan, Sina Matin, Christopher Steffen, Marc Nicolai, Dawn E. Sailer, David N. Herndon

Research output: Contribution to journalArticle

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Abstract

Burn injury in children is associated with low bone formation and long- term bone loss. Because recombinant human GH (rHGH) may accelerate burn wound healing, and because rHGH increases bone formation and density in GH- deficient patients, we studied the short-term effects of rHGH on bone formation, reflected by osteocalcin and type I procollagen propeptide levels in a randomized, double-blind, placebo-controlled study. Nineteen patients were enrolled and received either rHGH (0.2 mg/kg·day) or an equal volume of saline. Mean burn size and age were not different between the groups, and test substances were given from admission to time of wound healing (mean: 43 ± 22 days). At wound healing, serum levels of insulin-like growth factor (IGF)-1 and IGF binding protein (IGFBP)-3 in the rHGH group rose to mean values of 229% and 187% of the respective means of the placebo group (P < 0.025). Serum osteocalcin concentrations remained below normal in both groups, and type I procollagen propeptide levels achieved a low normal level. IGFBP-4 levels were twice that of normal on admission and doubled further at wound healing; IGFBP-5 levels were low on admission but rose to normal at wound healing. We conclude that large doses of rHGH were ineffective in improving disordered bone formation despite increasing serum IGF-1 and IGFBP- 3. The rHGH-independent rise in serum levels of the inhibitory binding protein IGFBP-4 suggests a mechanism by which improved bone formation is prevented despite successful elevation of IGF-1 and IGFBP-3 in the burned child.

Original languageEnglish (US)
Pages (from-to)21-24
Number of pages4
JournalJournal of Clinical Endocrinology and Metabolism
Volume83
Issue number1
DOIs
StatePublished - 1998

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Human Growth Hormone
Somatomedins
Osteogenesis
Growth Hormone
Bone
Biomarkers
Wound Healing
Insulin-Like Growth Factor Binding Protein 3
Wounds and Injuries
Serum
Insulin-Like Growth Factor Binding Protein 4
Insulin
Osteocalcin
Collagen Type I
Therapeutics
Insulin-Like Growth Factor Binding Protein 5
Placebos
Bone Density
Carrier Proteins
Bone and Bones

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology, Diabetes and Metabolism

Cite this

Effect of therapy with recombinant human growth hormone on insulin-like growth factor system components and serum levels of biochemical markers of bone formation in children after severe burn injury. / Klein, Gordon L.; Wolf, Steven E.; Langman, Craig B.; Rosen, Clifford J.; Mohan, Subburaman; Keenan, Bruce S.; Matin, Sina; Steffen, Christopher; Nicolai, Marc; Sailer, Dawn E.; Herndon, David N.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 83, No. 1, 1998, p. 21-24.

Research output: Contribution to journalArticle

Klein, Gordon L. ; Wolf, Steven E. ; Langman, Craig B. ; Rosen, Clifford J. ; Mohan, Subburaman ; Keenan, Bruce S. ; Matin, Sina ; Steffen, Christopher ; Nicolai, Marc ; Sailer, Dawn E. ; Herndon, David N. / Effect of therapy with recombinant human growth hormone on insulin-like growth factor system components and serum levels of biochemical markers of bone formation in children after severe burn injury. In: Journal of Clinical Endocrinology and Metabolism. 1998 ; Vol. 83, No. 1. pp. 21-24.
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AU - Klein, Gordon L.

AU - Wolf, Steven E.

AU - Langman, Craig B.

AU - Rosen, Clifford J.

AU - Mohan, Subburaman

AU - Keenan, Bruce S.

AU - Matin, Sina

AU - Steffen, Christopher

AU - Nicolai, Marc

AU - Sailer, Dawn E.

AU - Herndon, David N.

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N2 - Burn injury in children is associated with low bone formation and long- term bone loss. Because recombinant human GH (rHGH) may accelerate burn wound healing, and because rHGH increases bone formation and density in GH- deficient patients, we studied the short-term effects of rHGH on bone formation, reflected by osteocalcin and type I procollagen propeptide levels in a randomized, double-blind, placebo-controlled study. Nineteen patients were enrolled and received either rHGH (0.2 mg/kg·day) or an equal volume of saline. Mean burn size and age were not different between the groups, and test substances were given from admission to time of wound healing (mean: 43 ± 22 days). At wound healing, serum levels of insulin-like growth factor (IGF)-1 and IGF binding protein (IGFBP)-3 in the rHGH group rose to mean values of 229% and 187% of the respective means of the placebo group (P < 0.025). Serum osteocalcin concentrations remained below normal in both groups, and type I procollagen propeptide levels achieved a low normal level. IGFBP-4 levels were twice that of normal on admission and doubled further at wound healing; IGFBP-5 levels were low on admission but rose to normal at wound healing. We conclude that large doses of rHGH were ineffective in improving disordered bone formation despite increasing serum IGF-1 and IGFBP- 3. The rHGH-independent rise in serum levels of the inhibitory binding protein IGFBP-4 suggests a mechanism by which improved bone formation is prevented despite successful elevation of IGF-1 and IGFBP-3 in the burned child.

AB - Burn injury in children is associated with low bone formation and long- term bone loss. Because recombinant human GH (rHGH) may accelerate burn wound healing, and because rHGH increases bone formation and density in GH- deficient patients, we studied the short-term effects of rHGH on bone formation, reflected by osteocalcin and type I procollagen propeptide levels in a randomized, double-blind, placebo-controlled study. Nineteen patients were enrolled and received either rHGH (0.2 mg/kg·day) or an equal volume of saline. Mean burn size and age were not different between the groups, and test substances were given from admission to time of wound healing (mean: 43 ± 22 days). At wound healing, serum levels of insulin-like growth factor (IGF)-1 and IGF binding protein (IGFBP)-3 in the rHGH group rose to mean values of 229% and 187% of the respective means of the placebo group (P < 0.025). Serum osteocalcin concentrations remained below normal in both groups, and type I procollagen propeptide levels achieved a low normal level. IGFBP-4 levels were twice that of normal on admission and doubled further at wound healing; IGFBP-5 levels were low on admission but rose to normal at wound healing. We conclude that large doses of rHGH were ineffective in improving disordered bone formation despite increasing serum IGF-1 and IGFBP- 3. The rHGH-independent rise in serum levels of the inhibitory binding protein IGFBP-4 suggests a mechanism by which improved bone formation is prevented despite successful elevation of IGF-1 and IGFBP-3 in the burned child.

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