A battery of steroidal and nonsteroidal antirheumatic drugs and protease inhibitors were tested by intraarticular injection for effects on osteoarthritis of the knees of rabbits subjected to partial lateral meniscectomy and section of the sesamoid and collateral fibular ligaments. Among the standard drugs, only the glucocorticoid, triamcinolone hexacetonide, and the protease inhibitor, tranexamic acid, exhibited significant anti-osteoarthritic activity. An experimental drug, GPA 2163, also offered some protection against joint degeneration. The nonsteroidal antiinflammatory drugs had no effect on the development of osteoarthritis in the model.In a previous report from this laboratory, a new surgical method for experimental induction of osteoarthritis (OA) in rabbits was described (1). This method, which involves partial lateral meniscectomy and section of the sesamoid and collateral ligaments, induces a relatively consistent and reproducible degenerative disease of rabbit knees in a period of 6 weeks. A battery of selected steroidal drugs, nonsteroidal antiinflammatory drugs (NSAIDs), and other drugs reputed to possess antirheumatic properties or otherwise influence connective tissues have subsequently been tested for systemic efficacy in retarding or reversing the cartilage deterioration in knees of rabbits subjected to the new procedure (2). A few drugs exerted marked to moderate anti-OA activity. These included the steroids, paramethasone and triamcinolone, only 2 of 11 NSAlDs tested (pirprofen and the experimental drug, CGS 5391B), the glucofuranoside derivative, tribenoside, and the anti-estrogen, tamoxifen. The anti-osteoarthritic activity could not be explained in terms of known antiinflammatory or other properties of these drugs.In the present study, additional selected drugs have been tested for possible anti-OA efficacy by direct intraarticular (IA) injection in laterally meniscectomized rabbits.
MATERIALS AND METHODSMale New Zealand white rabbits (Hare Farms) weighing approximately 4 kg each were subjected to partial lateral meniscectomy with section of the fibular collateral and sesamoid ligaments or sham operation, as previously described (1). The animals were maintained on a diet of standard rabbit pellets and tap water ad libitum.Intraarticular injections into the knee joint of test drugs or vehicle were given either as a single 0.0s ml dose 7 days post-surgery or as two 0.05 ml doses on days 7 and 14 post-surgery. The injections were made using 0.25-ml glass syringes and 26-gauge one-half-inch needles for soluble drugs or 23-gauge one-half-inch needles for suspensions. The source, dosage, and vehicle used for each test drug are shown in Table 1. One drug, triamcinolone hexacetonide, was also injected periarticularly (PA) in one group of rabbits (i.e., the compound was injected into the soft tissue immediately adjacent to the knee joint).In each rabbit tested, the right (operated) knee was injected with drug, while the left (unoperated) knee was injected with vehicle only, as a test for possible i...
