Effects of pulse methylprednisolone on bone and marrow tissues. Corticosteroid‐induced osteonecrosis in rabbits

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Abstract
Objective. To investigate the effects of pulse methylprednisolone acetate on bone and bone marrow tissues and to clarify the causal factors of corticosteroidinduced osteonecrosis (ON) by using an experimental animal model. Methods. Male adult Japanese white rabbits were injected once with 20 mg/kg of methylprednisolone into the right gluteus medius muscle. Seven rabbits were killed at 4 weeks, 4 at 6 weeks, 4 at 8 weeks, and 6 at 10 weeks. Both histopathologic and hematologic studies were performed every week. Results. By 4 weeks after the steroid injection, 43% of the rabbits studied had developed multifocal ON lesions in the femur and/or humerus. In 1 rabbit, a thrombus was detected in an arteriole adjacent to the necrotic area at 4 weeks. After 6 weeks, there was also progressive histologic evidence of revascularization, with granulation tissue, and osteoblastic repair, with appositional bone formation. Hyperlipemia, fatty liver, and intraosseous fat embolism were observed in conjunction with thrombocytopenia and hypofibrinogenemia. Conclusion. A single injection of high-dose corticosteroids was found to be capable of inducing thrombocytopenia, hypofibrinogenemia, and hyperlipemia with multifocal ON in several bones.