EFFECTS OF A SYNTHETIC VITAMIN-D ANALOG, ED-71, ON BONE DYNAMICS AND STRENGTH IN CANCELLOUS AND CORTICAL BONE IN PREDNISOLONE-TREATED RATS

To determine the action of corticosteroid on bone metabolism and asses s the effects of a synthetic vitamin D analog, ED-71, on them, 56 SD r ats, 8 weeks of age, were assigned to seven groups of eight animals ea ch. Group 1 was the basal control. Group 2 was the nontreated control. Groups 3-7 were given prednisolone at 30 mg/kg of body weight (BW) tw ice a week and concomitantly administered ED-71 with respective doses of 0, 0.0125, 0.025, 0.05, and 0.1 mu g/kg of BW for 12 weeks. In grou p 3, urinary calcium (U-Ca) and deoxypyridinoline (U-Dpy) were signifi cantly increased compared,vith group 2. In groups 4-7, U-Ca values wer e increased but U-Dpy values were dose-dependently decreased. Age-depe ndent increases in the parameter values of BMD, compressive strength, trabecular bone volume (BV/TV), and trabecular thickness (Tb.Th) of th e lumbar body were significantly suppressed in group 3 but dose-depend ently increased in groups 4-7, and the values of group 7 exceeded thos e of group 2. The parameters of bane mineral density (BMD) and the ben ding strength of the femur in groups 4-7 were larger than the values i n group 3 but did not reach the levels of group 2. The trabecular bone formation rate (BFR/BS) of the lumbar body measured by calcein labeli ng in group 3 was reduced when compared with group 2, but the values w ere not further decreased in groups 4-7. The perimeter ratios of doubl e labels over single labels (dLS/sLS) greatly decreased by prednisolon e, were dose-dependently increased to the level of the normal control by ED-71. Double-labeled perimeters and the dLS/sLS ratios were also i ncreased in the periosteal envelope of the midfemur. These findings cl early demonstrate that prednisolone administration affects the age-rel ated changes in bone metabolism, and ED-71 administration counteracts the effects by increasing intestinal calcium absorption, reducing bone resorption, and enhancing mineralization. The action of ED-71, howeve r, seems to be less potent in the cortical bone.