No abstract

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 DLbuthionine-(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.Although it has been shown that oxidative stress is related to osteonecrosis (1-3), the details of its pathogenesis remain unclear. Animal models are needed to clarify the pathophysiology of osteonecrosis and to establish prophylactic treatment strategies. Although previously rabbit models have been most commonly used for the study of osteonecrosis (1-5), we recently hypothesized that models of induced osteonecrosis in rats, which are particularly well suited for genetic studies, would be of greater use. We have previously demonstrated that subcutaneous injection of DL-buthionine-(S,R)-sulfoximine (BSO) in rats on consecutive days was by itself sufficient to induce osteonecrosis (6). However, when BSO is administered to rats for 14 consecutive days, oxidative stress persists for 14 days, making it unclear whether, as in steroid-induced osteonecrosis, osteonecrosis occurs as a single event or whether it results from cytotoxicity associated with chronic oxidation. The mechanisms underlying the process from oxidation induction to the development of osteonecrosis continue to be obscure, and we consider this type of model inadequate to explore them.Steroid-induced osteonecrosis can occur after a single exposure to these agents, and in a model using rabbits administered steroids, oxidation has been shown to also develop soon after a single exposure (2,3). This suggests to us the need for a rat model in which the development of osteonecrosis after a single application of oxidative stress can be reliably observed, to clarify the mechanisms underlying the development of steroidinduced osteonecrosis. We ...