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骨关节炎中的可溶性生物标志物。

Soluble biological markers in osteoarthritis.

作者信息

Rousseau Jean-Charles, Chapurlat Roland, Garnero Patrick

机构信息

INSERM Unit 1033, Pavillon F, Hôpital E. Herriot, 5 Place d'Arsonval, 69437 Lyon Cedex 03, France.

Biochemical Marker Assay Laboratory for Clinical Research (PMO-Lab), Lyon, France.

出版信息

Ther Adv Musculoskelet Dis. 2021 Sep 29;13:1759720X211040300. doi: 10.1177/1759720X211040300. eCollection 2021.

Abstract

In recent years, markers research has focused on the structural components of cartilage matrix. Specifically, a second generation of degradation markers has been developed against type II collagen neoepitopes generated by specific enzymes. A particular effort has been made to measure the degradation of minor collagens III and X of the cartilage matrix. However, because clinical data, including longitudinal controlled studies, are very scarce, it remains unclear whether they will be useful as an alternative to or in combination with current more established collagen biological markers to assess patients with osteoarthritis (OA). In addition, new approaches using high-throughput technologies allowed to detect new types of markers and improve the knowledge about the metabolic changes linked to OA. The relative advances coming from phenotype research are a first attempt to classify the heterogeneity of OA, and several markers could improve the phenotype characterization. These phenotypes could improve the selection of patients in clinical trials limiting the size of the studies by selecting patients with OA characteristics corresponding to the metabolic pathway targeted by the molecules evaluated. In addition, the inclusion of rapid progressors only in clinical trials would facilitate the demonstration of efficacy of the investigative drug to reduce joint degradation. The combination of selective biochemical markers appears as a promising and cost-effective approach to fulfill this unmet clinical need. Among the various potential roles of biomarkers in OA, their ability to monitor drug efficacy is probably one of the most important, in association with clinical and imaging parameters. Biochemical markers have the unique property to detect changes in joint tissue metabolism within a few weeks.

摘要

近年来,标志物研究聚焦于软骨基质的结构成分。具体而言,已针对特定酶产生的II型胶原新表位开发了第二代降解标志物。人们尤其致力于测量软骨基质中次要胶原III和X的降解情况。然而,由于包括纵向对照研究在内的临床数据非常匮乏,目前尚不清楚它们能否作为评估骨关节炎(OA)患者的替代指标,或者与现有的更成熟的胶原生物标志物联合使用。此外,利用高通量技术的新方法能够检测新型标志物,并增进对与OA相关的代谢变化的了解。来自表型研究的相关进展是对OA异质性进行分类的首次尝试,一些标志物能够改善表型特征描述。这些表型能够在临床试验中优化患者选择,通过挑选具有与所评估分子靶向的代谢途径相对应的OA特征的患者,限制研究规模。此外,仅将快速进展者纳入临床试验将有助于证明研究药物减少关节退变的疗效。选择性生化标志物的联合使用似乎是满足这一未满足临床需求的一种有前景且具成本效益的方法。在生物标志物在OA中的各种潜在作用中,与临床和影像学参数相关联,其监测药物疗效的能力可能是最重要的作用之一。生化标志物具有在几周内检测关节组织代谢变化的独特特性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8c29/8488516/1a7a8586e905/10.1177_1759720X211040300-fig1.jpg

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