Introduction: The purpose of this study was to investigate the effects of combination treatments with anticoagulant (warfarin) and a lipid-lowering agent (probucol) on the prevention of steroid-associated osteonecrosis (ON) in rabbits.

Materials and Methods: Male adult Japanese white rabbits were intramuscularly injected once with 20mg/kg body weight of methylprednisolone acetate into the right gluteus medius muscle. These rabbits were divided into three groups: a warfarin plus probucol treatment group (WP Group, n=25), a probucol treatment group (PR Group, n=30), and a non-prophylactic treatment group (NP Group, n=20). Two weeks after the cortico-steroid injection, both femora and humeri were histopathologically examined for the presence of ON, and the sizes of bone marrow fat cells were morphologically examined.

Results: The incidence of ON in the WP Group (5%) was significantly lower than that in the NP Group (70%) (p < 0.0001). The incidence of ON in the PR Group (37%) was significantly lower than that in the NP Group (p < 0.05), but it was significantly higher than that in the WP Group (p < 0.01). The mean size of the bone marrow fat cells was significantly smaller in the WP Group (53.5 ± 4.1μm) than that in the NP Group (60.0 ± 4.0μm) (p < 0.0001). There were no significant differences in the size of bone marrow fat cells between the WP and the PR Groups (52.0 ± 5.0μm).

Discussion: This study experimentally confirmed that anticoagulant plus lipid-lowering agent treatment has a preventative effect on steroid-associated ON in rabbits.