The ultimate hope of researchers and patients is a pathway to development of treatments for osteoarthritis to modify the disease process in addition to the symptoms. However, development of disease modifying drugs requires objective endpoints such as measures of joint structure, joint tissue homeostasis and/or joint survival-measures such as provided by imaging biomarkers, molecular biomarkers and joint replacement frequency, respectively. Although biomarkers supporting investigational drug use and drug approval include surrogate endpoints that may not necessarily reflect or directly correlate with the clinical outcome of interest, a formal biomarker qualification process currently exists that is a rigorous three stage process that yields biomarker approvals (or denials) for specific contexts of use. From a cost perspective, biochemical biomarkers are the 'ones to beat'; however, even well-validated biomarkers may not cross the translation gaps for eventual use in healthcare unless they offer an advantage in terms of cost per quality adjusted life year. This review summarizes the case FOR and AGAINST biomarkers in drug development and highlights the current data for a subset of biomarkers in the osteoarthritis research field informing on cartilage homeostasis, joint inflammation and altered subchondral bone remodeling.

中文翻译：

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骨关节炎：当前的分子生物标志物和前进的道路。

研究人员和患者的最终希望是开发治疗骨关节炎的途径，以在症状之外改变疾病过程。然而，疾病改善药物的开发需要客观终点，例如关节结构的测量、关节组织稳态和/或关节存活测量，例如分别由成像生物标志物、分子生物标志物和关节置换频率提供。尽管支持研究药物使用和药物批准的生物标志物包括不一定反映或直接与感兴趣的临床结果相关的替代终点，但目前存在正式的生物标志物资格认证过程，该过程是一个严格的三阶段过程，可产生生物标志物批准（或拒绝）特定的使用环境。从成本来看，生化生物标志物是“要击败的”；然而，即使经过充分验证的生物标志物也可能无法跨越最终用于医疗保健的转化差距，除非它们在每个质量调整生命年的成本方面提供优势。本综述总结了药物开发中 FOR 和 AGAINST 生物标志物的案例，并强调了骨关节炎研究领域中生物标志物子集的当前数据，这些数据为软骨稳态、关节炎症和软骨下骨重塑改变提供了信息。