Risk factors for developing osteonecrosis after prophylaxis in steroid-treated rabbits

Abstract

Objective: Both abnormal lipid metabolisms and coagulopathy have been suggested to be associated with the development of steroid-induced osteonecrosis (ON). We examined plasma risk factors for development of steroid-induced ON in rabbits after prophylaxis with a lipid-lowering agent and/or an anticoagulant.

Methods: Seventy adult male rabbits were injected intramuscularly once with 20 mg/kg methylprednisolone acetate. Fifty-five rabbits received prophylaxis with probucol (a lipid-lowering agent; n = 20) or warfarin (an anticoagulant; n = 14) or both (n = 21). Probucol and warfarin were administered beginning 1 to 2 weeks prior to steroid injection. Two weeks after steroid injection, the bilateral femora and humeri were examined histopathologically for the presence of ON. Based on a logistic regression model, laboratory variables before steroid injection were assessed to determine whether they demonstrated any association with the risk of ON.

Results: Twenty-one rabbits developed ON. In the univariate analyses, significant positive associations were observed between plasma concentrations of triglyceride and low-density lipoprotein and the risk of development of ON. In the multivariate model, only the plasma triglyceride level suggested a positive association. Even after adjusting for probucol and warfarin use, the plasma triglyceride level was still suggested to be a predictor for development of ON. Rabbits with higher baseline triglyceride levels had a more pronounced triglyceride increase in their response to steroids.

Conclusion: Our study suggests that, after prophylaxis with probucol and/or warfarin, plasma triglyceride level is associated with the development of steroid-induced ON in rabbits.