LABORATORY AND ANIMAL STUDIES

Combination Treatment with Warfarin plus Probucol Prevents Steroid-Induced Osteonecrosis in Rabbits
G Motomura, T Yamamoto, K Miyanishi, Y Iwamoto
Department of Orthopaedic Surgery, Graduate School of Medical Science,
Kyushu University, Kyushu, Japan

Objective: The purpose of this study is to investigate the effects of combination treatment with anticoagulant (warfarin) and a lipid-lowering agent (probucol) on the prevention of steroid-induced osteonecrosis (ON) in rabbits.

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, including warfarin plus probucol treatment group (WP Group, n=25), probucol treatment group (PR Group, n=30), and non-prophylactic treatment group (NP Group, n=20). Two weeks after the corticosteroid 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 WP Group (5%) was significantly lower than that in NP Group (70%) (p < 0.0001). The incidence of ON in PR Group (37%) was significantly lower than that in NP Group (p < 0.05), but it was significantly higher than that in WP Group (p < 0.01). The mean size of bone marrow fat-cells was significantly smaller in WP Group (53.5 ± 4.1µm) than that in NP Group (60.0 ± 4.0µm) (p < 0.0001). There were no significant differences in the size of bone marrow fat-cells between WP and PR Groups (52.0 ± 5.0µm).

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