Mechanism of bone-loss in the glucocorticoid induced osteonecrosis

Background: Glucocorticoid(GC) is often utilized as a therapy for connective tissue diseases and autoimmune diseases. But a portion of patients administered GC would be suffering from avascular necrosis of femoral head (AVN). Therefore, it is quite necessary to study its mechanism thoroughly. Objective: To investigate the mechanism of bone-loss in the glucocorticoid(GC) induced osteonecrosis. Design: Randomized controlled experimental study. Setting and participants: This experiment was performed in the Department of Orthopaedics, Chinese PLA General Hospital. Thirty-one New Zealand white adult rabbits of either gender, weighing 3.0 to 4.0 kg, were purchased from Laboratory Animal Centre of Chinese PLA General Hospital, and 21 patients [ aged (48.30 ± 6.09) years old ] as pathological samples were selected and all of them were confirmed to have glucocorticoid induced osteonecrosis. Interventions: A model of glupaedic. cocorticoid induced osteonecrosis was duplicated according to Yamamoto's method. And the changes of the relationship between the expression of OPG/osteoclast generation inhibitive factors(OCIF) and osteoclast differentiation as well as bone-loss were observed, by the examinations of pathology, bone-loss and immunohistochemiscal staining. The biopsy samples from 21 patients with glucocorticoid induced osteonecrosis were collected, immunohistochemistry stained, the local OPG/OCIF protein expression changes were examined in osteonecrosis femoral head. Main outcome measures: Bone mineral density of experimental groups, as well as the local OPG/OCIF protein expression changes in osteonecrosis femoral head. Results: After the administration of glucocorticoid, the local OPG expression gradually reduced(P < 0.01) and the number of osteoclasts obviously increased, followed by local gradual hone-loss(P < 0.05); and the local OPG expression of patients with osteonecrosis was obviously lower than that of healthy control subject. Conclusion: It has been clarified both in animal model and clinical data that the administration of glucocorticoid inhibits the local OPG expression of bone, and facilitates osteoclasts' abnormal proliferation which results in the bone-loss.