Systemic administration of rhIGF-I or rhIGF-I/IGFBP-3 increases cortical bone and lean body mass in ovariectomized rats.

Abstract

The purpose of this study was to compare dose-related effects on cortical bone and lean body mass following subcutaneous administration of rhIGF-I alone, or bound to an equimolar amount of rhIGFBP-3 to adult Ovx rats. At the age of 16 weeks, rats were ovariectomized or sham-operated and were allowed 8 weeks to develop osteopenia. After being divided into control (saline treated) or treatment groups, rats were injected daily during an 8-week period with 0.9 and 2.6 mg/kg of rhIGF-I, or with 0.9, 2.6, and 7.5 mg/kg of rhIGF-I bound to rhIGFBP-3. Fluorescent bone markers were given 9 and 2 days prior to necropsy. Body weights and lean body mass were monitored throughout the experiment. Cortical bone histomorphometry was performed on tibial cross-sections at the tibiofibular junction, and endochondral bone growth was measured at the distal femoral metaphysis. All rats treated with rhIGF-I or the rhIGF-I/IGFBP-3 complex had increased body weights, corresponding to a dose-dependent increase in lean body mass. Endochondral growth was slightly increased in all experimental groups, but was not dose-dependent. A dramatic increase in periosteal, modeling-dependent formation, coupled with decreased or unchanged resorption on the endocortical envelope resulted in a dose-dependent increase in cortical thickness and cross-sectional area in groups treated with the complex of rhIGF-I/IGFBP-3. This complex appeared to be more effective in promoting positive musculoskeletal changes than rhIGF-I alone.(ABSTRACT TRUNCATED AT 250 WORDS)

• Authors: C M Bagi, E DeLeon, R Brommage, S Adams, D Rosen, A Sommer
• Journal: Bone (Bone) Vol. 16 Issue 4 Suppl Pg. 263S-269S (Apr 1995) ISSN: 8756-3282 [Print] United States
• PMID: 7542899 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Carrier Proteins
• Growth Inhibitors
• Insulin-Like Growth Factor Binding Proteins
• Recombinant Proteins
• Somatomedins
• Insulin-Like Growth Factor I

Topics

• Absorptiometry, Photon
• Animals
• Body Weight (drug effects)
• Bone Density (drug effects)
• Bone Development (drug effects, physiology)
• Bone Diseases, Metabolic (drug therapy, physiopathology)
• Bone Resorption (drug therapy)
• Carrier Proteins (administration & dosage, pharmacology)
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Female
• Growth Inhibitors (administration & dosage, pharmacology)
• Insulin-Like Growth Factor Binding Proteins
• Insulin-Like Growth Factor I (administration & dosage, pharmacology)
• Muscle, Skeletal (drug effects)
• Ovariectomy
• Rats
• Rats, Sprague-Dawley
• Recombinant Proteins (administration & dosage, pharmacology)
• Somatomedins (administration & dosage, pharmacology)
• Tibia (drug effects, physiology)