POSSIBLE INVOLVEMENT OF VITAMIN-D3-DEFICIENCY AND RELATIVELY ENHANCEDBONE-RESORPTION IN THE DEVELOPMENT OF BONE LOSS IN STREPTOZOTOCIN-INDUCED DIABETIC RATS

To explore the pathogenesis of diabetes associated osteopenia, we char acterized the osteopenia in streptozotocin(STZ)-diabetic rats pharmaco logically and biochemically. The femur metaphyseal bone mineral densit y measured by single photon absorptiometry decreased time-dependently in the STZ rats compared with that in control, and the difference reac hed statistical significance from 2 weeks after treatment with STZ. Cl osely similar bone loss was obtained in ovariectomized(Ovx) and vitami n D deficient(D(-)) rats. Daily oral treatment with a bone resorption inhibitor, FR78844(a bisphosphonate compound, 100 mg/kg), for 4 weeks significantly attenuated the osteopenia in the STZ and Ovx rats, but n ot in the D(-) rats, while 1 alpha-hydroxyvitamin D3(l alpha-(OH)D3) s ignificantly attenuated the osteopenia in the STZ and D(-) rats in a d ose of 0.1 mu g/kg/day, and that in the Ovx rats in 1 mu g/kg/day. The latter dose of 1 alpha-(OH)D3 significantly increased the metaphyseal bone mineral density of the femur in normal rats. Serum levels of 1 a lpha, 25-dihydroxyvitamin D(1 alpha, 25-(OH)2D), the most active metab olite of vitamin D, hardly changed in the Ovx rats compared with that in control, but decreased to 24 and 76 % that of control in the STZ an d D(-) rats, respectively. Serum PTH levels in the STZ, Ovx and D(-) r ats were comparable with those in controls, but serum calcitonin level s were reduced to 60 and 66 % of control in the STZ and Ovx rats, resp ectively. Serum osteocalcin levels also decreased in the STZ rats comp ared to control. It is thus speculated that the predominance of bone r esorption over bone formation and the reduction of 1 alpha, 25-(OH)2D are involved in the pathogenesis of diabetes associated osteopenia.