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 assess the effects of a synthetic vitamin D analog, ED-71, on them, 56 SD rats, 8 weeks of age, were assigned to seven groups of eight animals each. 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) twice a week and concomitantly administered ED-71 with respective doses of 0, 0.0125, 0.025, 0.05, and 0.1 μg/kg of BW for 12 weeks. In group 3, urinary calcium (U-Ca) and deoxypyridinoline (U-Dpy) were significantly increased compared with group 2. In groups 4–7, U-Ca values were increased but U-Dpy values were dose-dependently decreased. Age-dependent increases in the parameter values of BMD, compressive strength, trabecular bone volume (BV/TV), and trabecular thickness (Tb.Th) of the lumbar body were significantly suppressed in group 3 but dose-dependently increased in groups 4–7, and the values of group 7 exceeded those of group 2. The parameters of bone mineral density (BMD) and the bending strength of the femur in groups 4–7 were larger than the values in 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 labeling in group 3 was reduced when compared with group 2, but the values were not further decreased in groups 4–7. The perimeter ratios of double labels over single labels (dLS/sLS) greatly decreased by prednisolone, were dose-dependently increased to the level of the normal control by ED-71. Double-labeled perimeters and the dLS/sLS ratios were also increased in the periosteal envelope of the midfemur. These findings clearly demonstrate that prednisolone administration affects the age-related 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, however, seems to be less potent in the cortical bone.