Osteonecrosis Development in a Novel Rat Model Characterized by a Single Application of Oxidative Stress

Objective. To investigate the relationship between transient oxidative stress and the development of osteonecrosis in a rat model. Methods. A total of 160 male Wistar rats (24 weeks old) were injected only once with the pro-oxidant DL-buthionine-(S,R)-sulfoximine (BSO) (500 mg/kg given intraperitoneally) and were killed 12 hours (group A), 1 day (group B), 3 days (group C), 4 days (group D), 5 days (group E), 7 days (group F), or 14 days (group G) after administration (n = 20 per group). Twenty untreated rats were used as a control group (group N). Femurs were examined histopathologically for the presence of osteonecrosis, and reduced glutathione (GSH) in liver tissue was measured as an index of oxidative stress. Results. GSH decreased rapidly after BSO administration. Significant decreases were noted in groups A and B as compared to group N (P < 0.0001 and P = 0.0007, respectively), confirming the development of transient extreme oxidative stress soon after BSO administration. The histopathologic study revealed osteonecrosis in 10% of the rats in group E, 35% of the rats in group F, and 40% of the rats in group G. Conclusion. Transient extreme oxidative stress was confirmed to induce osteonecrosis in this model. Since preparation of this model is extremely simple and because rats are well suited to genetic studies, this model may be of use in elucidating the pathophysiology of femoral head osteonecrosis in future studies.