Effects of cyclosporin A on the development of osteonecrosis in rabbits

Acta Orthop. 2006 Oct;77(5):813-9. doi: 10.1080/17453670610013042.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cyclosporine / administration & dosage*
  • Dose-Response Relationship, Drug
  • Femur Head Necrosis / chemically induced
  • Femur Head Necrosis / etiology*
  • Femur Head Necrosis / prevention & control
  • Glucocorticoids / administration & dosage
  • Immunosuppressive Agents / administration & dosage*
  • Methylprednisolone / administration & dosage
  • Organ Transplantation / adverse effects*
  • Rabbits

Substances

  • Glucocorticoids
  • Immunosuppressive Agents
  • Cyclosporine
  • Methylprednisolone