Apoptotic Cell Death in Steroid Induced Osteonecrosis: an Experimental Study in Rabbits

Objective: We investigated apoptosis, i.e., programmed cell death, in steroid induced osteonecrosis in a rabbit model.

Methods: Forty-four adult Japanese White rabbits were divided into 3 groups: Group A were untreated controls and had a subsequent 8 week no-treatment period; Group B received intramuscular injection of methylprednisolone 4 mg/kg once weekly for 4 weeks; and Group C received the same treatment and had a subsequent 8 week no-treatment period. At the end of each period, all animals were sacrificed and tissue samples were obtained from the femur and humerus for histopathologic examination. Terminal deoxynucleotidyl transferase (TdT) mediated deoxyuridine triphosphate (dUTP) biotin nick end labeling (TUNEL) was used to detect fragmented DNA known to be associated with apoptotic cell death.

Results: Group A rabbits did not develop osteonecrosis-like lesions (ONL) in the femur and humerus, and few TUNEL positive cells were observed in bone marrow cells. In Group B, ONL developed in 11/15 rabbits, and many TUNEL positive cells were found in the area surrounding ONL. In Group C, ONL were found in 6/10 rabbits, but only a few TUNEL positive cells were present around the lesion.

Conclusion: These findings revealed that apoptosis occurs in the early stage of steroid induced osteonecrosis.