膝骨关节炎的新兴疗法。
完整摘要 · 中文译文
膝骨关节炎（OA）是OA最常见的形式，也是全球慢性疼痛和残疾的主要原因。其不断增长的负担主要由衰老和肥胖驱动，并与重大的社会成本和心血管死亡率增加相关。膝OA现被认识到是一种异质性全关节疾病，涉及生物力学、代谢、炎症、骨软骨和神经血管机制。这种复杂性有助于解释为什么现有镇痛药疗效有限，以及为什么疾病修饰性OA药物开发屡次受挫。尽管如此，治疗格局正在迅速演变。新兴的症状性策略包括基于肠促胰素的疗法（司美格鲁肽是首个显示出对疼痛和功能具有实质性益处的药物）、神经营养因子调节、关节内缓释糖皮质激素、润滑注射剂和影像引导的神经血管干预。与此同时，候选的疾病修饰性OA药物靶向软骨合成代谢、Wnt信号、基质降解酶、软骨下骨重塑、免疫代谢途径和局部基因治疗。包括局部给予GLP1受体激动剂、合成代谢药物TPX-100和关节内IL-1受体拮抗剂基因治疗在内的若干疗法已显示出令人鼓舞的信号，而间充质基质细胞疗法迄今在III期临床试验中表现出不一致的疗效，凸显了进一步标准化间充质基质细胞产品和优化患者选择的必要性。最近的进展预示着向一种m的转变 更多样化的膝骨关节炎治疗前景，出现了同时针对症状和疾病潜在机制的新机会。
完整摘要 · 英文原文
Knee osteoarthritis (OA) is the most prevalent form of OA and a leading cause of chronic pain and disability worldwide. Its growing burden, driven mainly by ageing and obesity, is associated with major societal costs and increased cardiovascular mortality. Knee OA is now recognized as a heterogeneous whole-joint disease involving biomechanical, metabolic, inflammatory, osteochondral and neurovascular mechanisms. This complexity helps to explain why existing analgesics have modest efficacy and why disease-modifying OA drug development has repeatedly faltered. The therapeutic landscape is nevertheless evolving rapidly. Emerging symptomatic strategies include incretin-based therapies (semaglutide is the first to show substantial benefits for pain and function), neurotrophin modulation, extended-release intra-articular glucocorticoids, lubricating injectables and image-guided neurovascular interventions. In parallel, candidate disease-modifying OA drugs target cartilage anabolism, Wnt signalling, matrix-degrading enzymes, subchondral bone remodelling, immunometabolic pathways and local gene therapy. Several treatments, including locally administered GLP1 receptor agonists, the anabolic agent TPX-100 and intra-articular IL-1 receptor antagonist gene therapy, have shown encouraging signals, whereas mesenchymal stromal cell therapies have thus far demonstrated inconsistent efficacy across phase III clinical trials, highlighting the need for further standardization of mesenchymal stromal cell products and optimization of patient selection. Recent advances signal a shift towards a more diverse therapeutic landscape for knee OA, with emerging opportunities to target both symptoms and the underlying mechanisms of disease.