Effects of methylprednisolone on bone formation and resorption in rats

Excessive glucocorticoids induce osteoporosis. However, there is some controversy regarding the mechanism of action, and even the endpoint result. The present study was carried out to obtain further insight into the action of glucocorticoids on bone formation and resorption in rats. Growing rats were injected subcutaneously with methylprednisolone (mPSL) at doses of 0, 2.5, 5, 10 or 20 mg/kg per day for 4 weeks. Bone mineral density (BMD), enchondral and periosteal bone formation, collagen synthetic activities of osteoblasts, numbers of osteoblasts and osteoclasts, and serum markers to assess bone turnover were determined. Administration of mPSL dose-dependently increased the BMD in the tibial metaphysis, while it dose-dependently decreased the BMD in the diaphysis. Both enchondral and periosteal bone formation were decreased in a dose-dependent fashion. The incorporation and secretion of (3)H-proline by osteoblasts were both decreased in trabecular and cortical bones. The number of osteoclasts, together with the number of osteoblasts, in the tibial metaphysis was drastically decreased. Serum alkaline phosphatase and osteocalcin were decreased at higher doses. These results support the recent notion that glucocorticoids inhibit both bone formation and resorption. In addition, BMD as an endpoint result might differ from site to site in bone due to a different balance between bone formation and resorption.