Effects of some nonsteroidal antiinflammatory drugs on proteoglycan metabolism and organization in canine articular cartilage

The effects of several nonsteroidal antiinflammatory drugs, used at concentrations achievable in synovial fluid, on human osteoarthritic (OA) cartilage metalloprotease activity in vitro was studied. Acetaminophen and ketoprofen had no effect; sodium salicylate, indomethacin, and diclofenac slightly decreased proteoglycanase activity. Piroxicam and tenoxicam suppressed proteoglycanase activity by 48.2% and 68.3%, respectively, and suppressed collagenase activity by 19.1 % and 36.8%, respectively. Use of these NSAIDs may help to decrease cartilage catabolism in patients with OA.Nonsteroidal antiinflammatory drugs (NSAIDs) are commonly used in the treatment of patients with osteoarthritis (OA), but their effects on articular cartilage metabolism and the course of human OA remains a subject of debate. It is believed that some NSAIDs, principally, salicylates and indomethacin, accelerate OA cartilage destruction by impairing proteoglycan synthesis by chondrocytes, while others have a chondroprotective effect (1-5). Theoretically, NSAIDs could help slow down the enhanced catabo-

Section: Brief Report In Vitro Effect O F Nonsteroidal Antiinflammatomentioning

confidence: 68%

In Vitro Effect of Nonsteroidal Antiinflammatory Drugs on Proteoglycanase and Collagenase Activity in Human Osteoarthritic Cartilage

Vignon

Mathieu

Louisot

et al. 1991

“…It is noteworthy that IA injections of potent prostaglandin synthetase inhibitors, such as pirprofen and phenylbutazone, did not exacerbate the degenerative joint disease. Others have postulated that such drugs might be harmful in the long run to the cartilage of patients sufferihg from OA (24). However, the obvious benefits of the analgesic effects of most NSAIDs in degenerative joint disease cannot be discounted, even though they may have no effect on the progress of the basic degradation of cartilage.…”

Section: Discussionmentioning

confidence: 99%

A new model of osteoarthritis in rabbits

Butler¹,

Colombo²,

Hickman³

et al. 1983

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...

“…Suppression of proteoglycan biosynthesis has also been demonstrated in vitro and in vivo by indomethacin [67-731, phenylbutazone [67,70,721, fenoprofen [74], flufenamic acid [75], and tolmetin [72, 761.…”

Section: Therapeutic Control Of Cartilage Degradationmentioning

confidence: 99%

“…Benoxaprofen [77], diclofenac [71,721, and sulindac sulphide [74] have been reported to protect articular cartilage in animal models of arthropathy. On the other hand, piroxicam [78] and tiaprofenic acid [79] are considered to have no deleterious effects on cartilage at concentrations where strong antiinflammatory effects were produced by these drugs.…”

Section: Therapeutic Control Of Cartilage Degradationmentioning

confidence: 99%

Articular cartilage: What it is, why it fails in osteoarthritis, and what can be done about it

Ghosh

1988

Articular cartilage covers the ends of long bones and together with synovial fluid is responsible for the remarkably efficient mechanical properties of synovial joints. In osteoarthritis (OA) joint articular cartilage fails. While the etiology of cartilage failure in OA is still controversial, some of the mechanisms responsible for loss of proteoglycans from these tissues have been identified and offer insights for potential avenues of therapeutic control. Many non‐steroidal antiinflammatory drugs (NSAIDs), although effective at suppressing the symptoms of OA, do little to support the attempts by chondrocytes to replenish proteoglycan loss from the extracellular matrix. However, evidence is now accumulating, largely from studies using animal models, that not all antiarthritic agents are deleterious to cartilage. Some may even promote those anabolic processes necessary for its repair and restoration of function. These recent developments offer a more optimistic approach for the therapeutic management of the osteoarthritic patient in the future.