Oxidative stress and vascular permeability in steroid-induced osteonecrosis model

We focused on the role of oxidative stress in the pathogenesis of steroid-induced osteonecrosis (ON) and the possibility of preventing this condition by antioxidant administration. Methylprednisolone 4 mg/kg was injected only once into Japanese white rabbits. The involvement of oxidative stress and the presence/absence of bone circulatory impairment were investigated in groups of 10 rabbits killed at 3, 5, and 14 days each and in 10 rabbits administered the antioxidant glutathione. Reduced blood glutathione and lipid peroxide levels were determined biochemically, and the presence/absence of advanced glycation end-product expression was determined immunohistochemically. Vascular permeability in bone was confirmed by finding albumin leakage into the stroma. These blood biochemical and immunohistochemical studies clarified that the oxidative stress in this model developed 3-5 days after steroid administration. Elevated vascular permeability was observed in the 5- and 14-day groups. Hence, circulatory disturbance in bone was noted 5 days after steroid administration, coinciding with the onset of oxidative stress. The rate of ON development, which was 70% in the steroid-alone 14-day group, was significantly reduced to 0% in the steroid + antioxidant group. These results suggest the involvement of oxidative stress and vascular permeability in this steroid-induced ON model and the possibility of its prevention by suppression of oxidative stress.