New biochemical insights into the pathogenesis of osteoarthritis and the role of laboratory investigations in clinical assessment.

Osteoarthritis (OA) is among the most frequent diseases in the population and a common cause of pain and disability in adults. The principal disease hallmarks for assessment of OA are still clinical observation and radiographic aspects. However, the efficacy of therapeutic interventions is complicated by the time required to observe radiographic signs, useful for both diagnosis and assessment. Thus, laboratory markers have received growing attention in recent years, in an attempt to improve diagnosis, assessment of disease activity and severity, and evaluation of therapeutic effects. Many biomarkers have been proposed, in particular those reflecting cartilage and bone turnover and synovitis. Among these, COMP, antigenic keratan sulphate, hyaluronan, YKL-40, type III collagen N-propeptide, and urinary glucosyl-galactosyl pyridinoline appear to be the most promising. However, serum or urinary determinations of these molecules are difficult to interpret adequately due to their complex metabolism. New ultrasensitive methods for C-reactive protein have improved the usefulness of this marker, especially in the assessment of disease activity. Routine examination of synovial fluid is still essential for diagnosis and includes leukocyte count and crystal detection; specialized testing includes the evaluation of the levels of markers of local inflammation such as metalloproteinases and cytokines, which appear to be crucial to the pathogenesis of OA.