Insulin-like growth factor I as a predictor of cortical bone mass in a long-term study of ovariectomized and estrogen-treated rats

The relationship between serum insulin-like growth factor I (IGF-I) and cortical bone mass, formation and resorption and length of bone in a long-term experiment on intact, ovariectomized and estrogen-treated/substituted rats was studied by using multiple linear regression analysis. The study comprised intact rats killed at 2, 6, 9, 12, 15, and 24 months of age, rats ovariectomized 6 months old and killed at 9, 12, 15, and 24 months of age, and intact and ovariectomized rats treated with a low dose of estrogen for 8 months before they were killed at 24 months of age. Serum IGF-I, bone length and total, subperiosteal and subendocortical bone mass in mid-diaphyseal cross sections of the femur were determined. Changes in the latter two variables, respectively, represent the net result of subperiosteal bone formation and subendocortical bone resorption. Multiple linear regression analysis showed that IGF-I was a positive determinant of cortical bone mass and subperiosteal bone formation. In aged rats, IGF-I was also a positive determinant of bone length, whereas IGF-I was not found to be a determinant of suben-docortical bone resorption. The analyses showed that longterm treatment of aged rats with a low dose of estrogen had a dual effect on cortical bone by inhibiting subperiosteal formation and subendocortical resorption. The results revealed a relationship between endogenous circulating IGF-I and local anabolic actions of the growth factor in bones. Thus, IGF-I may be a valuable serum marker of cortical bone formation and length of long bones when considering estrogendepleted and estrogen-treated rats.