PREDNISOLONE ALONE, OR IN COMBINATION WITH ESTROGEN OR DIETARY CALCIUM DEFICIENCY OR IMMOBILIZATION, INHIBITS BONE-FORMATION BUT DOES NOT INDUCE BONE LOSS IN MATURE RATS

Glucocorticoid use has long been recognized as a risk factor for bone loss, resulting in an increased fracture incidence in humans, However, steroid-treated patients often present with other complications that predispose to bone loss, such as immobilization, and little is known a bout the interaction of these other risk factors for bone loss and glu cocorticoids. In the present study, mature female rats were treated wi th prednisolone (Pred) or vehicle, in combination with ovariectomy (ov x), dietary calcium deficiency (LoCa), or right hind limb immobilizati on (IM). After 4 weeks of treatment, the rats were killed and the righ t tibia and tibiofibular junction were collected for quantitative hist omorphometric analysis and the right femur was collected for bone mine ral density (BMD) and mechanical strength determinations, As expected, ovx, LoCa, and IM decreased BMD in the distal femur and cancellous bo ne volume (CnBV/TV) in the proximal tibia, All Pred-treated groups res ponded with increases of BMD and CnBV/TV, when compared to their respe ctive non-Pred treated groups, Mechanical strength testing of the canc ellous bone of the distal femur reflected the changes in BMD and CnBV/ TV, No differences in trabecular plate thickness were noted in any of the treatment groups, The Pred group showed a significant reduction in longitudinal growth rate, as well as bone formation rate (BFR/BS), in the proximal tibia when compared with their respective control groups , the latter indicated by a decrease in both mineralizing surface and mineral apposition rate, Most notably, osteoclast surface and urinary free pyridinoline, a bone resorption marker, increased significantly w ith each of the three risk factors, Pred treatment inhibited these inc reases but it did not exert significant reductions when used by itself At the tibiofibular junction, there were no measurable changes in eit her total bone or cortical bone area, Endocortical BFR/BS were increas ed by ovx or LoCa but each was lowered by Pred treatment, Periosteal B FR/BS were increased by ovx and IM, and Pred exerted significant inhib ition by itself and in combination with other risk factors, We conclud e, therefore, that unlike the effects observed in humans treated with glucocorticoid, treatment of rats with prednisolone not only does not result in bone loss but may exert a protective effect on the skeleton through the inhibition of bone resorption. (C) 1997 by Elsevier Scienc e Inc. All rights reserved.