EFFECTS OF DIACERHEIN IN AN ACCELERATED CANINE MODEL OF OSTEOARTHRITIS

Object: To determine whether diacerhein has a disease-modifying effect in an accelerated canine model of osteoarthritis. Design: Fourteen ad ult mongrel dogs underwent unilateral L4-S1 dorsal root ganglionectomy (DRG), followed 3 weeks later by ipsilateral anterior cruciate ligame nt transection. Seven dogs received diacerhein (15-20 mg/kg) daily thr oughout the interval between DRG and sacrifice, eight weeks after liga ment transection. The other seven dogs served as OA controls. Results: The mean volume of synovial fluid obtained from the OA knee of the di acerhein-treated dogs was approximately 40% less than that from the OA knee of the controls. In addition, diacerhein appeared to reduce the severity of fibrillation (femoral condyle) and full-thickness ulcerati on (trochlear ridge) of the articular cartilage and the level of colla genase activity in extracts of the OA cartilage, and to increase net P CT synthesis in the OA cartilage, although none of the above changes w ere statistically significant. Conclusion: The differences between the diacerhein group and untreated OA controls, even though not statistic ally significant, suggest that diacerhein was active in this rapidly p rogressive model of OA. Because changes associated with initiation of OA may be different than those associated with progression, whether di acerhein has a disease-modifying effect should be examined in a less r apidly progressive model.