Diacerhein treatment reduces the severity of osteoarthritis in the canine cruciate-deficiency model of osteoarthritis

Objective. To determine if diacerhein protects against the early stages of joint damage in a canine model of osteoarthritis (OA). Methods. OA was induced in 20 adult mongrel dogs by transection of the ante rior cruciate ligament of the left knee. Beginning the day after surgery, d ogs in the active treatment group were dosed twice a day with capsules of d iacerhein, providing a total daily dose of 40 mg/kg, for 32 weeks. Dogs in the control group received placebo capsules on the same schedule. Pathology in the unstable knee was assessed arthroscopically 16 weeks after surgery and by direct observation when the dogs were killed 32 weeks after surgery. The severity of gross joint pathology was recorded, and samples of the med ial femoral condyle cartilage and the synovial tissue adjacent to the centr al portion of the medial meniscus were collected for histologic evaluation. Water content and uronic acid concentration of the articular cartilage fro m the femoral condyle were determined, and collagenolytic activity in extra cts of cartilage pooled from the medial and lateral tibial plateaus was ass ayed against C-14-labeled collagen fibers. Results. Diacerhein treatment slowed the progression of OA, as measured by grading of gross changes in the unstable knee at arthroscopy 16 weeks after cruciate ligament transection (P = 0.04) and at the time the animals were killed, 32 weeks after surgery (P = 0.05). However, 32 weeks after ACL tran section, the mean proteoglycan concentration and water content of the OA ca rtilage and the level of collagenolytic activity in extracts of the cartila ge were not significantly different in the diacerhein treatment group than in the placebo treatment group. Conclusion. Diacerhein treatment significantly reduced the severity of morp hologic changes of OA compared with placebo. These findings support the vie w that diacerhein may be a disease-modifying drug for OA.