Effects of cyclosporin A on the development of osteonecrosis in rabbits.
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.


CONCLUSIONS
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.
Miyanishi
Keita
K
Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kyushu University, Higashi-ku, Fukuoka, 812-8582, Japan. keitamiya@jcom.home.ne.jp
Yamamoto
Takuaki
T
Irisa
Takahiko
T
Yamashita
Akihisa
A
Motomura
Goro
G
Jingushi
Seiya
S
Iwamoto
Yukihide
Y
D000818:Animals; D016572:Cyclosporine / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D005271:Femur Head Necrosis / Q000139:chemically induced / Q000209:etiology* / Q000517:prevention & control; D005938:Glucocorticoids / Q000008:administration & dosage; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D008775:Methylprednisolone / Q000008:administration & dosage; D016377:Organ Transplantation / Q000009:adverse effects*; D011817:Rabbits
D005938:Glucocorticoids; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D008775:Methylprednisolone