Garnero Patrick, Delmas Pierre D
INSERM Research Unit 403, Lyon, France.
Curr Opin Rheumatol. 2003 Sep;15(5):641-6. doi: 10.1097/00002281-200309000-00020.
Osteoarthritis is a chronic disease characterized by progressive destruction of articular cartilage and subchondral bone, and synovial reaction. Clinical and radiologic findings that form the basis of the diagnosis of osteoarthritis are poorly sensitive for monitoring the progression of the disease. Biologic markers reflecting quantitative and dynamic changes of joint tissue turnover represent promising adjunct tools.
New tissue-specific markers have been developed and include assays for type II collagen synthesis and degradation and synovitis. Prospective studies indicate that increased or decreased levels of some of these markers are associated with rapid progression of joint destruction in patients with knee osteoarthritis. Because progression of joint damage is likely to result primarily from an imbalance between degradation and reparative processes, a combination of markers reflecting these two components appears promising. For example, combining two new markers for type II collagen synthesis and degradation in an uncoupling index of cartilage turnover was more effective in predicting 1-year radiologic progression in knee osteoarthritis than the measurement of a single marker. Preliminary data in rheumatoid arthritis show a rapid response of a marker of type II collagen degradation under disease-modifying antirheumatic drugs, with early changes of this marker being predictive of long-term radiologic progression.
Recent evidence suggests that the combination of some biologic markers will be useful for identifying patients at risk for rapid joint destruction in osteoarthritis. Because of their rapid changes under treatment, biologic markers will play an important role in the development and monitoring of new structure-modifying therapies for osteoarthritis.
骨关节炎是一种以关节软骨、软骨下骨的进行性破坏以及滑膜反应为特征的慢性疾病。构成骨关节炎诊断基础的临床和放射学检查结果对于监测疾病进展的敏感性较差。反映关节组织更新的定量和动态变化的生物标志物是很有前景的辅助工具。
已开发出新型组织特异性标志物,包括检测II型胶原合成与降解以及滑膜炎的方法。前瞻性研究表明,其中一些标志物水平的升高或降低与膝骨关节炎患者关节破坏的快速进展相关。由于关节损伤的进展可能主要源于降解与修复过程之间的失衡,反映这两个组成部分的标志物组合似乎很有前景。例如,将两种新的II型胶原合成与降解标志物结合成软骨更新的解偶联指数,在预测膝骨关节炎1年的放射学进展方面比单一标志物测量更有效。类风湿关节炎的初步数据显示,在改善病情抗风湿药物作用下,II型胶原降解标志物有快速反应,该标志物的早期变化可预测长期放射学进展。
最近的证据表明,一些生物标志物的组合将有助于识别骨关节炎中存在关节快速破坏风险的患者。由于其在治疗下的快速变化,生物标志物将在骨关节炎新的结构改善疗法的开发和监测中发挥重要作用。