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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 Injury¹

Departments of Pediatrics (G.L.K., B.S.K.) and Surgery (S.E.W., Si.M., D.N.H.), University of Texas Medical Branch and the Shriners Burns Institute (G.L.K., S.E.W., Si.M., M.N., D.N.H.), Galveston, Texas 77555; Nephrology Division, Children’s Memorial Hospital and the Northwestern University Medical School (C.B.L., D.E.S.), Chicago, Illinois 60614; the Maine Center for Osteoporosis Research, St. Joseph Hospital (C.J.R., C.S.), Bangor, Maine 04401; and the Jerry L. Pettis VA Medical Center and Loma Linda University School of Medicine (Su.M.), Loma Linda, California 92357

Address all correspondence and requests for reprints to: Gordon L. Klein, M.D., Pediatric Gastroenterology Division, Room 3.240B, Children’s Hospital, University of Texas Medical Branch, 301 University Boulevard, Galveston, Texas 77555-0352. E-mail: gklein{at}utmb.edu

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.