Effects 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

• Published in: The journal of clinical endocrinology and metabolism 1998-01, Vol.83 (1), p.21-24
• Main Authors: Klein, G L, Wolf, S E, Langman, C B, Rosen, C J, Mohan, S, Keenan, B S, Matin, S, Steffen, C, Nicolai, M, Sailer, D E, Herndon, D N
• Format: Article
• Language: English
• Subjects: Biomarkers - blood; Bone Density - drug effects; Bone Development - drug effects; Burns - blood; Burns - physiopathology; Burns - therapy; Child; Child, Preschool; Double-Blind Method; Female; Human Growth Hormone - therapeutic use; Humans; Insulin-Like Growth Factor Binding Protein 3 - blood; Insulin-Like Growth Factor Binding Protein 4 - blood; Insulin-Like Growth Factor Binding Protein 5 - blood; Insulin-Like Growth Factor Binding Proteins - blood; Insulin-Like Growth Factor I - metabolism; Male; Osteocalcin - blood; Recombinant Proteins - therapeutic use; Spine; Wound Healing
• ISSN: 0021-972X

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 fomation, 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 IGFBR-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.