BENEFIT OF SYSTEMICALLY ADMINISTERED RHIGF-I AND RHIGF-I IGFBP-3 ON CANCELLOUS BONE IN OVARIECTOMIZED RATS

The dose-related effects of systemically administered rhIGF-I and rhIG F-I/IGFBP-3 were monitored in the osteopenic rat skeleton at three dif ferent sites with cancellous bone: distal femoral metaphysis, epiphysi s, and lumbar vertebral bodies. At the age of 16 weeks, rats were bila terally ovariectomized (OVX) or sham operated (sham) and 8 weeks later divided into the control groups (sham OVX), and OVX groups treated wi th different doses of rhIGF-I or rhIGF-I/IGFBP-3 for 8 weeks. Fluoresc ent bone markers were given 9 and 2 days before necropsy. In addition, changes in designated bone sites as a result of ovariectomy alone wer e evaluated 8 and 16 weeks after surgery. High bone resorption, which dominates the postovariectomy remodeling process, resulted in a loss o f cancellous bone at all measured sites. The highest trabecular bone l oss was measured in the metaphyses (40%), compared with 22% in the lum bar vertebrae and 16% in the epiphyses. After 8 weeks of treatment wit h 7.5 mg/kg of rhIGF-I/IGFBP-3, bone formation rates were increased at all sites measured. Increased trabecular thickness was observed at th e epiphyses and in the lumbar vertebral bodies. Increased bone resorpt ion was restricted to the metaphyses of the rats that received the hig hest dose of rhIGF-I or rhIGF-I/IGFBP-3. Both formulations of rhIGF-I increased longitudinal bone growth similarly. This experiment demonstr ates site-specific differences in cancellous bone reactions following ovariectomy. Epyphyses showed some advantages for cancellous bone hist omorphometry over metaphyses and lumbar vertebral bodies. The data pre sented confirm the potential of rhIGF-I/IGFBP-3 complex to promote the bone formation process at various bone sites in osteoporotic rat skel eton.