Department of Molecular and Experimental Medicine, The Scripps Research Institute, , La Jolla, California, USA.
Ann Rheum Dis. 2013 Nov;72(11):1756-63. doi: 10.1136/annrheumdis-2013-203726. Epub 2013 Jul 29.
Osteoarthritis affects the whole joint structure with progressive changes in cartilage, menisci, ligaments and subchondral bone, and synovial inflammation. Biomarkers are being developed to quantify joint remodelling and disease progression. This article was prepared following a working meeting of the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis convened to discuss the value of biochemical markers of matrix metabolism in drug development in osteoarthritis. The best candidates are generally molecules or molecular fragments present in cartilage, bone or synovium and may be specific to one type of joint tissue or common to them all. Many currently investigated biomarkers are associated with collagen metabolism in cartilage or bone, or aggrecan metabolism in cartilage. Other biomarkers are related to non-collagenous proteins, inflammation and/or fibrosis. Biomarkers in osteoarthritis can be categorised using the burden of disease, investigative, prognostic, efficacy of intervention, diagnostic and safety classification. There are a number of promising candidates, notably urinary C-terminal telopeptide of collagen type II and serum cartilage oligomeric protein, although none is sufficiently discriminating to differentiate between individual patients and controls (diagnostic) or between patients with different disease severities (burden of disease), predict prognosis in individuals with or without osteoarthritis (prognostic) or perform so consistently that it could function as a surrogate outcome in clinical trials (efficacy of intervention). Future avenues for research include exploration of underlying mechanisms of disease and development of new biomarkers; technological development; the 'omics' (genomics, metabolomics, proteomics and lipidomics); design of aggregate scores combining a panel of biomarkers and/or imaging markers into single diagnostic algorithms; and investigation into the relationship between biomarkers and prognosis.
骨关节炎影响整个关节结构，软骨、半月板、韧带和软骨下骨以及滑膜炎症均发生进行性改变。目前正在开发生物标志物来定量评估关节重塑和疾病进展。本文是在欧洲临床和经济骨质疏松症和骨关节炎学会召开的一次工作会议之后编写的，该会议旨在讨论基质代谢生物标志物在骨关节炎药物研发中的价值。一般来说，最佳候选物是存在于软骨、骨或滑膜中的分子或分子片段，它们可能是特定于一种关节组织，也可能是所有关节组织共有的。目前研究的许多生物标志物与软骨或骨中的胶原代谢或软骨中的聚集蛋白聚糖代谢有关。其他生物标志物与非胶原蛋白、炎症和/或纤维化有关。骨关节炎生物标志物可使用疾病负担、研究性、预后、干预效果、诊断和安全性分类进行分类。有许多有前途的候选物，尤其是尿Ⅱ型胶原 C 端肽和血清软骨寡聚蛋白，但没有一种具有足够的区分能力，可以区分个体患者和对照（诊断），或区分不同疾病严重程度的患者（疾病负担），预测有或没有骨关节炎的个体的预后（预后），或一致性如此之高，以至于可以作为临床试验中的替代终点（干预效果）。未来的研究方向包括探索疾病的潜在机制和开发新的生物标志物；技术发展；组学（基因组学、代谢组学、蛋白质组学和脂质组学）；将一组生物标志物和/或成像标志物组合成单个诊断算法的综合评分设计；以及研究生物标志物与预后之间的关系。
