Effects of cyclosporin A on the development of osteonecrosis in rabbits

Abstract

Background Osteonecrosis (ON) of the femoral head is a serious complication in patients who have undergone organ transplantation. Introduction of cyclosporin A has resulted in lower-dosage steroid treatment and a decrease in the occurrence of ON. We examined the effect of cyclosporin A on the development of ON in rabbits. Methods In experiment A, rabbits were given cyclosporin A and 20 mg/kg methylprednisolone acetate. The control group was given 20 mg/kg methylprednisolone acetate only. Experiment B was then performed to mimic the clinical situation in which the use of cyclosporin A and lower steroid doses resulted in a decrease in occurrence of ON. In Experiment C, the effects of treatment with cyclosporin A only on development of ON were examined. 4 weeks after injection, bilateral femora and humeri were examined histopathologically for ON. Results Cyclosporin A increased the incidence of ON in rabbits when given in combination with steroid (p = 0.04). No ON lesions were observed in rabbits treated with cyclosporin A alone. Interpretation Our findings suggest that the clinically reported reduction in occurrence of ON following the use of cyclosporin A is probably attributable to the lower steroid doses used.