Rheumatology Department, Lariboisière Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France.
Inserm U1132, UFR de médecine, Université de Paris, Paris, France.
Nat Rev Rheumatol. 2020 Dec;16(12):673-688. doi: 10.1038/s41584-020-00518-6. Epub 2020 Oct 29.
The prevalence of osteoarthritis (OA) and the burden associated with the disease are steadily increasing worldwide, representing a major public health challenge for the coming decades. The lack of specific treatments for OA has led to it being recognized as a serious disease that has an unmet medical need. Advances in the understanding of OA pathophysiology have enabled the identification of a variety of potential therapeutic targets involved in the structural progression of OA, some of which are promising and under clinical investigation in randomized controlled trials. Emerging therapies include those targeting matrix-degrading proteases or senescent chondrocytes, promoting cartilage repair or limiting bone remodelling, local low-grade inflammation or Wnt signalling. In addition to these potentially disease-modifying OA drugs (DMOADs), several targets are being explored for the treatment of OA-related pain, such as nerve growth factor inhibitors. The results of these studies are expected to considerably reshape the landscape of OA management over the next few years. This Review describes the pathophysiological processes targeted by emerging therapies for OA, along with relevant clinical data and discussion of the main challenges for the further development of these therapies, to provide context for the latest advances in the field of pharmaceutical therapies for OA.
骨关节炎（OA）的患病率以及与该病相关的负担在全球范围内稳步上升，这代表着未来几十年内面临的主要公共卫生挑战。OA 缺乏特定的治疗方法，这使其被认为是一种严重的疾病，存在未满足的医疗需求。对 OA 病理生理学的认识的提高，使人们能够确定多种潜在的治疗靶点，这些靶点涉及 OA 的结构进展，其中一些具有前景，并正在随机对照试验中进行临床研究。新兴的治疗方法包括针对基质降解蛋白酶或衰老软骨细胞的治疗方法，这些方法可以促进软骨修复或限制骨重塑、局部低度炎症或 Wnt 信号通路。除了这些具有潜在的 OA 疾病修饰作用的药物（DMOADs）之外，还有一些靶点正在被探索用于治疗 OA 相关疼痛，如神经生长因子抑制剂。这些研究的结果预计将在未来几年内极大地改变 OA 管理的格局。本综述描述了新兴 OA 治疗方法所针对的病理生理过程，以及相关的临床数据和对这些治疗方法进一步发展的主要挑战的讨论，为 OA 药物治疗领域的最新进展提供了背景。
