THE EFFECTS OF RECOMBINANT HUMAN INSULIN-LIKE GROWTH-FACTOR (RHIGF)-1AND RHIGF-1 IGF BINDING PROTEIN-3 ADMINISTRATION ON RAT OSTEOPENIA INDUCED BY OVARIECTOMY WITH CONCOMITANT BILATERAL SCIATIC NEURECTOMY

We compared the effect of administration of recombinant human insulin- like growth factor-1 (rhIGF-1) alone or the rhIGF-1/IGF binding protei n-3 (IGFBP-3) complex on osteopenia in rats. Female Sprague-Dawley rat s (8 months old) underwent combined ovariectomy and bilateral sciatic neurectomy (OVX-NX) or sham operation only, After 2 months, the OVX-NX animals were injected subcutaneously with rhIGF-1 alone or with rhIGF -1/IGFBP-3 equimolar complex for 4 weeks. The IGF-1 contents and dose were 0.3 mg/kg of body weight (BW) three times/week, 3 mg/kg of BW onc e/week, or 3 mg/kg of BW three times/week At the end of the experiment , the 4th and 5th lumbar vertebrae (L4, L5) and the proximal tibiae we re removed after tetracycline labeling, and histomorphometrical analys es were performed on undecalcified sections using Villanueva's stainin g, The cancellous bone volume at L5 significantly increased by thicken ing of the trabecular aidth in rats treated with the complex, However, the increase in the values at the proximal tibia was not significant. The bone formation rates (BFR/BS) in the lumbar vertebrae of rats tre ated,vith the complex three times a week at doses of 0.3 mg/kg of BW a nd 3 mg/kg of BW were both significantly increased but the parameter i ncrease was less marked with the dose of 3 mg/kg of BW once/week The B FR/BS did not increase significantly in animals treated with IGF-1 alo ne. These findings clearly demonstrated that the effect of systemicall y administered rhIGF-1 on bone formation was markedly potentiated when combined with IGFBP-3 in estrogen deficiency combined with reduced ac tivity, The action of IGF-1 was less potent on the bone in paralyzed l imbs, The action of rhIGF-1/IGFBP-3 on trabecular bone appeared to dep end not only on the dose but also on the frequency of administration a nd the parts of the skeleton in rats.