Combined effects of an anticoagulant and a lipid-lowering agent on the prevention of steroid-induced osteonecrosis in rabbits

Objective. To investigate the effects of combination treatment with an anticoagulant (warfarin) plus a lipid-lowering agent (probucol) on the prevention of steroid-induced osteonecrosis (ON) in rabbits. Methods. Adult male Japanese white rabbits were injected once intramuscularly with 20 mg/kg of methylprednisolone acetate into the right gluteus medius muscle. The rabbits were then divided into 4 groups and treated as follows: one group received warfarin plus probucol (WP; n = 25), one received probucol alone (PA; n = 30), one received warfarin alone (WA; n = 26), and one received no treatment (nonprophylactic [NP]; n = 20). Two weeks after the steroid injection, the femora and humeri were examined histopathologically for the presence of ON. The sizes of the bone marrow fat cells were examined morphologically. Hematologic examinations were performed before and after the steroid injection. Results. The incidence of ON in the WP group (5%) was significantly lower than that observed in the NP group (70%). While the incidence rates of ON in the PA (38%) and WA (33%) groups were also significantly lower than that in the NP group, they were significantly higher than that observed in the WP group. The sizes of the bone marrow fat cells in both the WP (53.5 +/- 4.1 mum) and the PA (52.0 +/- 5.0 mum) groups were significantly smaller than those in the NP group (60.0 +/- 4.0 mum). We also observed a prolongation of the prothrombin time and a reduction in the plasma lipid levels in the WP group during the study. Conclusion. This study experimentally confirmed that the combined use of an anticoagulant and a lipid-lowering agent helps prevent steroid-induced ON in rabbits.