Stimulation of trabecular bone formation by insulin-like growth factor I in adult ovariectomized rats

Although in vitro experiments indicate that insulin-like growth factor I (IGF-I) is an anabolic hormone in bone cell metabolism, the effects of IGF-I in vivo on bone formation are unclear. We thus investigated whether IGF-I is able to stimulate bone formation in adult rats with established osteopenia induced by ovariectomy (OVX). IGF-I was administered at daily doses of 0.05, 0.2, and 0.8 mg/kg for 3 wk. OVX induced a marked osteopenia in femur and tibia. Administration of IGF-I increased trabecular bone mass with a maximal effect at 0.2 mg/kg. The same dose stimulated bone formation, as revealed by an increase in osteoid surface, osteoblast surface, triple tetracycline-labeled surface, and bone formation rate. The mineral apposition rate was equally stimulated at all doses. At the highest dose, IGF-I increased osteoclast surface and osteoclast number. These data indicate that, in the adult OVX rat, IGF-I stimulates bone formation and increases trabecular bone volume at medium doses and enhances the histological indexes of bone resorption at high doses.