SYSTEMIC ADMINISTRATION OF RHIGF-I OR RHIGF-I/IGFBP-3 INCREASES CORTICAL BONE AND LEAN BODY-MASS IN OVARIECTOMIZED RATS

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 I-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, The potential of the rhIGF-I/IGFBP-3 complex to increase lean body mass and cortical bone thickness in Ovx rats deserves further evaluation as a candidate for treatment of musculoskeletal disorders in humans.