Faculty Bibliography

Osteoarthritis (OA) can be a progressive, disabling disease, leading to diminished quality of life, and, for over 500,000 individuals annually in the US, total joint replacement. The etiology of OA will vary among individuals, with potential roles for systemic factors (such as genetics and obesity) as well as for local biomechanical factors (such as muscle weakness, joint laxity and traumatic injury). Joint deterioration occurs over extended periods of time, and the diverse molecular mechanisms that mediate pathogenic events of early, mid and late disease are not yet fully understood. The success of biologic therapies in the treatment of rheumatoid arthritis has demonstrated that the blockade of a single dominant cytokine or regulatory molecule can prevent cartilage destruction in a complex disease, and has raised expectations that mechanism-based treatments could also be developed for patients with OA. In this review, we will address the biological mechanisms that mediate structural damage in OA and examine current targets that are candidates for disease modification. The challenges to drug development and the obstacles to disease modification strategies will also be addressed

The osteoarthritis disease process affects not only the cartilage but also the entire joint structure, including the synovium, bone and periarticular muscles. Characteristically, abnormal biomechanical forces result in an imbalance between chondrocyte anabolic and catabolic pathways, which ultimately leads to progressive joint destruction. Within cartilage and synovium, pro-inflammatory cytokines, particularly IL-1b and TNF-a, auto-catalytically stimulate their own production and induce chondrocytes to produce additional catabolic mediators, including proteases, chemokines, nitric oxide, and prostaglandins. The success of targeted biological therapy in rheumatoid arthritis has taught that the blockade of a single dominant cytokine can lead to remarkable clinical benefit, even in complex disease. The effectiveness of biologicals in inflammatory arthritides as disease modifying agents has increased the likelihood that similar strategies can be developed to target specific molecular mechanisms in osteoarthritis (OA). However, since the clinical development program for disease-modifying OA drugs (DMOADs) is complicated by the slow progression of disease in many patients, the introduction of DMOADs will be greatly enhanced by advances in imaging and biomarkers that serve as validated surrogate endpoints for meaningful clinical outcomes

Though quantitative data might lead to improved information for clinical decisions, at the present time decisions in routine rheumatology practice generally are based largely on qualitative impressions, rather than on data. Patient questionnaires are readily accessible tools that the rheumatologist can use to go beyond impressions and to institute evidence-based guidelines appropriate to his or her own patient population and practice style. The Health Assessment Questionnaire (HAQ) and its derivatives have been shown to be the best predictors of functional and work disability, costs, joint replacement surgery, and mortality. Such questionnaires are at least as good as joint counts, radiographs, and laboratory tests in predicting these outcomes. Every encounter of a patient with a rheumatologist provides an opportunity to collect data. Based on experience with the Brooklyn Outcomes of Arthritis Registry Database, the author advocates distributing a waiting-room questionnaire to every patient who comes for an office visit. Potential benefits of recording questionnaire-based information include identifying trends or important changes in a patient's pain or physical function, providing a baseline for success with various treatment strategies for conditions of the rheumatologist's own practice, allowing patients an opportunity to express concerns, encouraging patients to disclose information they may feel is too minor to mention, and providing control data for research studies. A short questionnaire designed specifically for clinical, rather than research, use does not create a burden for office staff. Consistent use of patient questionnaires and systematic storage of the information gained can help document, track, and improve patient care in routine rheumatology practice