Grässel Susanne, Muschter Dominique
Department of Orthopedic Surgery, Exp. Orthopedics, ZMB/Biopark 1, Am Biopark 9, University of Regensburg, Regensburg, 93053, Germany.
F1000Res. 2020 May 4;9. doi: 10.12688/f1000research.22115.1. eCollection 2020.
Osteoarthritis (OA) is one of the most debilitating diseases and is associated with a high personal and socioeconomic burden. So far, there is no therapy available that effectively arrests structural deterioration of cartilage and bone or is able to successfully reverse any of the existing structural defects. Efforts to identify more tailored treatment options led to the development of strategies that enabled the classification of patient subgroups from the pool of heterogeneous phenotypes that display distinct common characteristics. To this end, the classification differentiates the structural endotypes into cartilage and bone subtypes, which are predominantly driven by structure-related degenerative events. In addition, further classifications have highlighted individuals with an increased inflammatory contribution (inflammatory phenotype) and pain-driven phenotypes as well as senescence and metabolic syndrome phenotypes. Most probably, it will not be possible to classify individuals by a single definite subtype, but it might help to identify groups of patients with a predominant pathology that would more likely benefit from a specific drug or cell-based therapy. Current clinical trials addressed mainly regeneration/repair of cartilage and bone defects or targeted pro-inflammatory mediators by intra-articular injections of drugs and antibodies. Pain was treated mostly by antagonizing nerve growth factor (NGF) activity and its receptor tropomyosin-related kinase A (TrkA). Therapies targeting metabolic disorders such as diabetes mellitus and senescence/aging-related pathologies are not specifically addressing OA. However, none of these therapies has been proven to modify disease progression significantly or successfully prevent final joint replacement in the advanced disease stage. Within this review, we discuss the recent advances in phenotype-specific treatment options and evaluate their applicability for use in personalized OA therapy.
骨关节炎（OA）是最使人衰弱的疾病之一，且与高昂的个人和社会经济负担相关。到目前为止，尚无有效疗法能够阻止软骨和骨骼的结构退化，或成功逆转任何现有的结构缺陷。为了确定更具针对性的治疗方案，人们努力开发了一些策略，能够从表现出明显共同特征的异质表型群体中对患者亚组进行分类。为此，该分类将结构内型分为软骨和骨亚型，它们主要由与结构相关的退行性事件驱动。此外，进一步的分类突出了炎症作用增加的个体（炎症表型）、疼痛驱动表型以及衰老和代谢综合征表型。很可能无法通过单一明确的亚型对个体进行分类，但这可能有助于识别具有主要病理特征的患者群体，这些患者更有可能从特定的药物或基于细胞的治疗中获益。目前的临床试验主要针对软骨和骨缺损的再生/修复，或通过关节内注射药物和抗体靶向促炎介质。疼痛大多通过拮抗神经生长因子（NGF）活性及其受体原肌球蛋白相关激酶A（TrkA）来治疗。针对代谢紊乱（如糖尿病）和衰老相关病理的疗法并未专门针对OA。然而，这些疗法均未被证明能显著改变疾病进展或成功预防晚期疾病阶段的最终关节置换。在本综述中，我们讨论了表型特异性治疗方案的最新进展，并评估了它们在个性化OA治疗中的适用性。
