SP0007 Osteoarthritis: new concepts of pathogenesis and management guidelines

Osteoarthritis (OA), the most common form of arthritis, is increasing in prevalence as the population ages. Osteoarthritic pathology occurs as a result of an imbalance between synthesis and repair (catabolic) processes. Synthesis, increased early in the osteoarthritic process, cannot keep pace with catabolic processes in which proteolytic and collagenolytic enzymes destroy cartilage matrix. Inflammation, the result of an interplay between cartilage breakdown and synovial reaction, increases in severity as the disease progresses. Current concepts suggest a specific role for the ageing process wherein formation of Advanced Glycation End-products (AGEs) increase with age, resulting in increased cross-linking of cartilage matrix components. AGEs also activate cytokines, adding to the inflammatory reaction. Genetic defects in type II collagen have been described. The most common mutation demonstrated is an error in one base leading to a substitution of cysteine for arginine in the collagen matrix, resulting in generalised precocious familial OA. Additional mutations have been described in other sites in type II collagen. Pain in OA results from multifactorial interplays, including inflammatory and non-inflammatory factors. Management is targeted to treating pain, improving function and disease modification. Symptomatic therapy includes simple analgesics, Cox-2 selective non-steroidal anti- inflammatory agents, traditional non-steroidal anti-inflammatory agents (with or without gastropathy-protective agents), and, at times, opiates. Cox-2 non-steroidal anti-inflammatory agents represent a significant advance in therapy, based on decreased peptic-ulcer-related gastropathy including haemorrhage, perforation or obstruction. Intra-articular steroids are helpful for acute flares. Intra-articular hyaluronans, an additional new modality, leads to relief of pain in OA of the knee in a significant number of patients; pain is relieved for prolonged periods of time, and therapy with repeated cycles is safe and effective. Hyaluronans are of particular benefit in patients in whom non-steroidal anti-inflammatory agents are not effective or well-tolerated. Nutraceuticals such as glucosamine and chondroitin sulfate have been shown to relieve pain in a number of studies, and, in some recent investigations, to modify the basic disease process. Agents which inhibit enzymatic or cytokine-induced breakdown and/or which stimulate matrix synthesis may lead to structure modification. Demonstration of such modification is difficult, and studies require several years duration. A number of agents appear to be disease – modifying in animal models, and successful disease-modification in humans is now considered tenable. Replacement of cartilage with autologous chondrocytes, or mesenchymal bone marrow stem cells shows promise for direct cartilage repair. References Altman RD, Hochberg MD, Moskowitz RW, Schnitzer TJ. Recommendations for the medical management of osteoarthritis of the hip and knee: 2000 update. Arthritis Rheum. 2000;43:1905–15 Crofford LJ, Lipsky PE, Brooks P, Abramson SB, Simon LS, vandePutte LBA. Basic biology and clinical application of specific cycloxygenase-2 inhibitors. Arthritis Rheum. 2000;43:4–13 Altman RD, Moskowitz RW. Intra-articular sodium hyaluronate (Hyalgan) in the treatment of patients with osteoarthritis of the knee: a randomized clinical trial. J Rheumatol. 1998;25:2203–12 Deal CL, Moskowitz RW. Nutraceuticals as therapeutic agents in osteoarthritis. Rheum Dis Clin North Am. 1999;25:379–95