Zhang Wei, Robertson William Brett, Zhao Jinmin, Chen Weiwei, Xu Jiake
School of Medicine, Southeast University, Nanjing, China.
Department of Integrative Medical Biology, Umeå University, Umeå, Sweden.
Front Endocrinol (Lausanne). 2019 Jul 2;10:431. doi: 10.3389/fendo.2019.00431. eCollection 2019.
Osteoarthritis (OA) is a degenerative joint disorder and one of the most prevalent diseases among the elderly population. Due to the limited spontaneous healing capacity of articular cartilage, it still remains challenging to find satisfactory treatment for OA. This review covers the emerging trends of pharmacologic therapies for OA such as traditional OA drugs (acetaminophen, non-steroidal anti-inflammatory drugs (NSAIDs), opioids, serotonin-norepinephrine reuptake inhibitors (SNRIs), intra-articular injections of corticosteroids, and dietary supplements), which are effective in pain relief but not in reversing damage, and are frequently associated with adverse events. Alternatively, disease-modifying drugs provide promising alternatives for the management of OA. The development of these emerging OA therapeutic agents requires a comprehensive understanding of the pathophysiology of OA progression. The process of cartilage anabolism/catabolism, subchondral bone remodeling and synovial inflammation are identified as potential targets. These emerging OA drugs such as bone morphogenetic protein-7 (BMP-7), fibroblast growth factor-18 (FGF-18), human serum albumin (HSA), interleukin-1 (IL-1) inhibitor, β-Nerve growth factor (β-NGF) antibody, matrix extracellular phosphoglycoprotein (MEPE) and inverse agonist of retinoic acid-related orphan receptor alpha (RORα) etc. have shown potential to modify progression of OA with minimal adverse effects. However, large-scale randomized controlled trials (RCTs) are needed to investigate the safety and efficacy before translation from bench to bedside.
骨关节炎(OA)是一种退行性关节疾病,也是老年人群中最常见的疾病之一。由于关节软骨的自发愈合能力有限,寻找令人满意的OA治疗方法仍然具有挑战性。本综述涵盖了OA药物治疗的新趋势,如传统的OA药物(对乙酰氨基酚、非甾体抗炎药(NSAIDs)、阿片类药物、5-羟色胺-去甲肾上腺素再摄取抑制剂(SNRIs)、关节内注射皮质类固醇和膳食补充剂),这些药物在缓解疼痛方面有效,但不能逆转损伤,且常伴有不良事件。另外,改善病情的药物为OA的治疗提供了有前景的替代方案。这些新兴OA治疗药物的开发需要全面了解OA进展的病理生理学。软骨合成代谢/分解代谢过程、软骨下骨重塑和滑膜炎症被确定为潜在靶点。这些新兴的OA药物,如骨形态发生蛋白-7(BMP-7)、成纤维细胞生长因子-18(FGF-18)、人血清白蛋白(HSA)、白细胞介素-1(IL-1)抑制剂、β-神经生长因子(β-NGF)抗体、基质细胞外磷酸糖蛋白(MEPE)和视黄酸相关孤儿受体α(RORα)的反向激动剂等,已显示出在副作用最小的情况下改变OA进展的潜力。然而,在从实验室转化到临床应用之前,需要进行大规模随机对照试验(RCT)来研究其安全性和有效性。