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 about the interaction of these other risk factors for bone loss and glucocorticoids. In the present study, mature female rats were treated with prednisolone (Pred) or vehicle, in combination with ovariectomy (ovx), dietary calcium deficiency (LoCa), or right hind limb immobilization (IM). After 4 weeks of treatment, the rats were killed and the right tibia and tibiofibular junction were collected for quantitative histomorphometric analysis and the right femur was collected for bone mineral density (BMD) and mechanical strength determinations. As expected, ovx, LoCa, and IM decreased BMD in the distal femur and cancellous bone volume (CnBV/TV) in the proximal tibia. All Pred-treated groups responded with increases of BMD and CnBV/TV, when compared to their respective non-Pred treated groups. Mechanical strength testing of the cancellous 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 with each of the three risk factors. Pred treatment inhibited these increases but it did not exert significant reductions when used by itself. At the tibiofibular junction, there were no measurable changes in either total bone or cortical bone area. Endocortical BFR/BS were increased by ovx or LoCa but each was lowered by Pred treatment. Periosteal BFR/BS were increased by ovx and IM, and Pred exerted significant inhibition by itself and in combination with other risk factors. We conclude, 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.