BoneKEy-Osteovision | Perspective
New biochemical markers of cartilage turnover in osteoarthritis: Recent developments and remaining challenges
Patrick Garnero
DOI:10.1138/20060244
Abstract
Osteoarthritis (OA) is characterized by progressive destruction of articular cartilage and by subchondral bone and synovial tissue reaction. Radiological findings are not sufficiently sensitive to detect early disease or to monitor the progression of joint damage. This article reviews recent developments in biochemical marker assays of cartilage turnover and explores their potential clinical uses in OA. Because type II collagen (CII) and aggrecan are the most abundant proteins in the cartilage matrix, efforts are centered on identifying biochemical markers of their synthesis and degradation. Assays for the N-terminal propeptides of procollagen IIA (PIIANP) and IIB (PIIBNP) have been developed to measure type II collagen synthesis. Degradation can be monitored by analyzing fragments from the helical (Helix-II, Col 2-1) or C-telopeptide (CTX-II) regions. Antibodies directed against the chief proteolytic cleavage sites of aggrecan by metalloproteases and aggrecanases have been generated and used in different assay formats. Although these new aggrecan markers have been useful in investigations of the biological pathways of cartilage turnover in in vitro and animal models, few of them have yet been carefully evaluated in patients with OA. Conversely, prospective studies suggest that systemic levels of some markers of type II collagen degradation (e.g., Helix-II and CTX-II) and synthesis (PIIANP) can predict disease progression in knee and hip OA, particularly when used in combination. An optimal panel of markers of cartilage, synovial tissue, and bone will certainly play an important role in the clinical development of new disease-modifying therapies and ultimately in the management of OA.
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