title: Combined treatment with GH and IGF-I: additive effect on cortical bone mass but not on linear bone growth in female rats.
abstract: The growth-promoting effect of combined therapy with GH and IGF-I in normal rats is not known. We therefore investigated the efficacy of treatment with recombinant human (rh)GH and/or rhIGF-I on longitudinal bone growth and bone mass in intact, prepubertal, female Sprague-Dawley rats. rhGH was injected twice daily sc (5 mg/kg·d) and rhIGF-I continuously infused sc (2.2 or 4.4 mg/kg·d) for 28 days. Longitudinal bone growth was monitored by weekly x-rays of tibiae and nose-anus length measurements, and tibial growth plate histomorphology was analyzed. Bone mass was evaluated by peripheral quantitative computed tomography. In addition, serum levels of IGF-I, rat GH, acid labile subunit, IGF binding protein-3, 150-kDa ternary complex formation, and markers of bone formation and degradation were measured. Monotherapy with rhGH was more effective than rhIGF-I (4.4 mg/kg·d) to increase tibia and nose-anus length, whereas combined therapy did not further increase tibia, or nose-anus, lengths or growth plate height. In contrast, combined rhGH and rhIGF-I (4.4 mg/kg·d) therapy had an additive stimulatory effect on cortical bone mass vs rhGH alone. Combined treatment with rhGH and rhIGF-I resulted in markedly higher serum IGF-I concentrations vs rhGH alone but did not compromise the endogenous secretion of GH. We conclude that rhIGF-I treatment augments cortical bone mass but does not further improve bone growth in rhGH-treated young, intact, female rats.
authors.affiliation: Pediatric Endocrinology Unit (K.S., T.C., C.C.-H., L.S.), Department of Women's and Children's Health, Karolinska Institutet, SE-17176 Stockholm, Sweden; and Centre for Bone and Arthritis Research (C.O.), Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, SE-41345 Gothenburg, Sweden.
authors.forename: Katja
authors.initials: K
authors.lastname: Sundström
authors.forename: Therese
authors.initials: T
authors.lastname: Cedervall
authors.forename: Claes
authors.initials: C
authors.lastname: Ohlsson
authors.forename: Cecilia
authors.initials: C
authors.lastname: Camacho-Hübner
authors.forename: Lars
authors.initials: L
authors.lastname: Sävendahl
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects; D001846:Bone Development / Q000187:drug effects*; D001842:Bone and Bones / Q000187:drug effects* / Q000378:metabolism; D004359:Drug Therapy, Combination; D004393:Dwarfism, Pituitary / Q000188:drug therapy; D005260:Female; D005947:Glucose / Q000378:metabolism; D013006:Growth Hormone / Q000097:blood; D019382:Human Growth Hormone / Q000494:pharmacology* / Q000627:therapeutic use; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D010902:Pituitary Gland / Q000187:drug effects; D017207:Rats, Sprague-Dawley
chemical_list: D018972:Insulin-Like Growth Factor Binding Protein 3; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D005947:Glucose