Dose Effects of Corticosteroids on the Development of Osteonecrosis in Rabbits

Objective. The relationship between dose of corticosteroids and the prevalence of osteonecrosis (ON) has not been established. We examined the dose effects of corticosteroids on the development of ON in a rabbit model. Methods. Rabbits were injected once intramuscularly with 1 (12 rabbits), 5 (12 rabbits), 20 (20 rabbits), and 40 (25 rabbits) mg/kg of methylprednisolone acetate (MPSL) into the right gluteus medius muscle. Four weeks after the MPSL injection, the proximal and distal parts of both the femora and humeri were histopathologically examined for the presence of ON. Hematological examinations were performed before and after the corticosteroid injection. Results. In rabbits with 1, 5, 20, and 40 mg/kg MPSL, the incidence of ON was 0, 42%, 70%, and 96%, respectively. The dose of MPSL showed a significant association with the incidence of ON. Histologically, reparative tissues around the ON sites were observed in the rabbits with 5 mg/kg MPSL, but not observed in rabbits with 20 and 40 mg/kg MPSL. On hematological examination, hyperlipidemia and thrombocytopenia were most apparent in the rabbits receiving 40 mg/kg MPSL. Conclusion. The study suggested that the dose of corticosteroids plays an important role in the development of ON in rabbits. The repair process was also found to be influenced by the dose of corticosteroids. Corticosteroid-induced hyperlipidemia and thrombocytopenia seemed to be associated with the incidence of ON. (First Release Oct 1 2008; J Rheumatol 2008;35:2395-9; doi: 10.3899/ jrheum.080324)