Interactions of insulin-like growth factor I with dexamethasone on trabecular bone density and mineral metabolism in rats

Abstract

Binz K, Schmid C, Bouillon R, Froesch ER, Jürgensen K, Hunziker EB. Interactions of insulin-like growth factor I with dexamethasone on trabecular bone density and mineral metabolism in rats. Eur J Endocrinol 1994;130:387–93. ISSN 0804–4643 Glucocorticoid treatment causes osteoporosis and growth retardation in humans. Insulin-like growth factor I (IGF-I) stimulates differentiation and replication of cultured osteoblast-like cells and induces longitudinal bone growth in IGF-I-deficient rats. We investigated the influence of subcutaneously infused IGF-I on bone and mineral metabolism of male rats treated with a high dose of dexamethasone. Dexamethasone was added to the drinking water in a concentration of 1 mg/l. After 30 days of dexamethasone treatment, recombinant human IGF-I (300 μg/day) or solvent was infused sc by osmotic minipumps for 21 days while dexamethasone was continued. Age-matched untreated male rats served as healthy controls. Dexamethasone-treated rats lost weight. Their IGF-I levels were decreased to 36% of healthy controls. Infusion of IGF-I resulted in an increase in IGF-I serum levels (582% compared to healthy controls) and allowed some weight gain. Osteocalcin and calcitriol levels were markedly decreased in dexamethasone-treated rats and were not influenced significantly by IGF-I infusion. In contrast, IGF-I treatment restored the free calcitriol concentration (molar ratio of calcitriol to vitamin D-binding protein) towards normal. Furthermore, infusion of IGF-I partially corrected the dexamethasone-induced hyperinsulinemia. Histomorphometric analysis revealed no difference in vertebral trabecular bone density (i.e. growth-independent bone remodeling) between the three groups. In contrast, mean trabecular bone density in tibial metaphyses was increased markedly by dexamethasone, presumably due to osteoclast inhibition. Insulin-like growth factor I infusion did not significantly influence these structural metaphyseal bone parameters. We conclude that IGF I-infusion in male rats treated with high doses of dexamethasone reduces insulin resistance and restores calcitriol production but not osteoblast function or responsiveness to calcitriol. K Binz, Division de Diabétologie, Hôpital Cantonal Universitaire, 1211 Geneva, Switzerland