title: 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.
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 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.
authors.affiliation: Department of Pediatrics, University of Texas Medical Branch, Galveston 77555-0352, USA. gklein@utmb.edu
authors.forename: G L
authors.initials: GL
authors.lastname: Klein
authors.forename: S E
authors.initials: SE
authors.lastname: Wolf
authors.forename: C B
authors.initials: CB
authors.lastname: Langman
authors.forename: C J
authors.initials: CJ
authors.lastname: Rosen
authors.forename: S
authors.initials: S
authors.lastname: Mohan
authors.forename: B S
authors.initials: BS
authors.lastname: Keenan
authors.forename: S
authors.initials: S
authors.lastname: Matin
authors.forename: C
authors.initials: C
authors.lastname: Steffen
authors.forename: M
authors.initials: M
authors.lastname: Nicolai
authors.forename: D E
authors.initials: DE
authors.lastname: Sailer
authors.forename: D N
authors.initials: DN
authors.lastname: Herndon
mesh_terms: D015415:Biomarkers / Q000097:blood; D015519:Bone Density / Q000187:drug effects; D001846:Bone Development / Q000187:drug effects*; D002056:Burns / Q000097:blood / Q000503:physiopathology / Q000628:therapy*; D002648:Child; D002675:Child, Preschool; D004311:Double-Blind Method; D005260:Female; D019382:Human Growth Hormone / Q000627:therapeutic use*; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood; D018974:Insulin-Like Growth Factor Binding Protein 4 / Q000097:blood; D018975:Insulin-Like Growth Factor Binding Protein 5 / Q000097:blood; D018969:Insulin-Like Growth Factor Binding Proteins / Q000097:blood*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008297:Male; D015675:Osteocalcin / Q000097:blood*; D011994:Recombinant Proteins / Q000627:therapeutic use; D013131:Spine; D014945:Wound Healing
chemical_list: D015415:Biomarkers; D018972:Insulin-Like Growth Factor Binding Protein 3; D018974:Insulin-Like Growth Factor Binding Protein 4; D018975:Insulin-Like Growth Factor Binding Protein 5; D018969:Insulin-Like Growth Factor Binding Proteins; D011994:Recombinant Proteins; D015675:Osteocalcin; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I