Acute-phase proteins in osteoarthritis

The joint destruction of osteoarthritis (OA) comprises loss of articular cartilage resulting from an imbalance of enzyme-catalized cartilage breakdown and regeneration. OA is thought to derive from defective chondrocyte metabolism and thus to inherently lack the large-scale systemic response that is the hallmark of rheumatoid arthritis (RA). Because of the apparent absence of systemic inflammation in OA, acute-phase response proteins have not been as extensively studied in OA as they have been in RA. The diagnosis of OA almost always involves radiographic assessment of joint damage, which is useful only after the disease process has been underway for several months. Radiographic evaluation cannot give a good assessment of current disease activity and is a relatively insensitive indicator of prognosis. Cartilage breakdown products can potentially serve as direct surrogate markers of OA disease activity, but have not been extensively used because of their limited sensitivity and the technical difficulties associated with their measurement. Markers of disease activity in RA are indirect and are derived from the acute-phase response, a cycle of temporal changes in cellular and metabolic function. The early part of the acute-phase response involves the local action and production of cytokines such as interleukin-1 (IL-1), tumor necrosis factor (TNF-alpha) and IL-6. In the late acute-phase response, these cytokines can effect many systemic changes, including increased production of acute-phase proteins (APP). Three valuable surrogate markers of disease activity in RA are provided by the acute-phase response: the time-honored erythrocyte sedimentation rate (ESR) and the newer APPs C-reactive protein (CRP) and serum amyloid A (SAA). As in RA, the joint destruction of OA involves IL-1, TNF-alpha, and IL-6; however, OA can be viewed as an indolent stimulus of the later (systemic) acute-phase response. Recent studies of the acute-phase response in OA suggest that the concentrations of CRP and SAA are elevated in OA, but to a lesser extent than in RA. In the future, long-term monitoring of CRP concentrations in the blood may permit the earlier detection and more effective treatment of OA.