Department of Medicine, McMaster University Faculty of Health Sciences, Hamilton, ON, Canada.
J Pharm Pharmacol. 2012 May;64(5):617-25. doi: 10.1111/j.2042-7158.2012.01458.x. Epub 2012 Feb 7.
Osteoarthritis (OA) of the knee and hip is among the most frequent and debilitating arthritic conditions. Aside from surgical intervention in severe cases, conventional treatment involves relieving painful symptoms with non-steroidal anti-inflammatory drugs (NSAIDs), narcotic and non-narcotic (weak) analgesics and physical therapy. To obtain insight into the extent of pathological changes in hip and knee OA we reviewed current literature on the pathogenesis of this state as a basis for current pharmacotherapy options.
Key features of the pathological joint changes in OA include: cartilage destruction by pro-inflammatory cytokines, matrix metalloproteinases and prostaglandins, which promote a catabolic environment; subchondral bone remodelling and resorption; hypertrophic differentiation of chondrocytes; neovascularisation of synovial tissue; and focal calcification of joint cartilage. Despite the central involvement of hyaline cartilage in OA pathogenesis, the source of pain likely stems from the richly innervated synovium, subchondral bone and periosteum components of the joint. Tissue damage during joint degeneration generates nociceptive stimuli. The presence of inflammatory mediators, including bradykinin, prostaglandins and leukotrienes, lowers the threshold of the Aδ and C pain fibres, resulting in a heightened response to painful stimuli.
It is our opinion that it is important to base and centre the management of OA patients on the severity of patient-important outcomes, rather than purely an assessment of damage to the joint. The joint damage, as interpreted from radiographs, is not necessarily representative of the symptoms experienced. The management of OA primarily comprises pharmacological therapy, surgical interventions and various non-pharmacological interventions.
膝和髋关节骨关节炎（OA）是最常见和最使人衰弱的关节炎之一。除了在严重情况下进行手术干预外，常规治疗还包括使用非甾体抗炎药（NSAIDs）、麻醉性和非麻醉性（弱）镇痛药和物理疗法来缓解疼痛症状。为了深入了解髋和膝关节 OA 的病理变化程度，我们回顾了当前关于这种疾病发病机制的文献，作为当前药物治疗选择的基础。
OA 关节病理变化的主要特征包括：促炎细胞因子、基质金属蛋白酶和前列腺素破坏软骨，促进分解代谢环境；软骨下骨重塑和吸收；软骨细胞的肥大分化；滑膜组织的新生血管形成；关节软骨的局灶性钙化。尽管透明软骨在 OA 发病机制中起核心作用，但疼痛的来源可能源于富含神经支配的滑膜、软骨下骨和关节的骨膜成分。关节退化过程中的组织损伤会产生伤害性刺激。炎症介质的存在，包括缓激肽、前列腺素和白三烯，降低了 Aδ和 C 痛觉纤维的阈值，导致对疼痛刺激的反应增强。
我们认为，将 OA 患者的管理基于患者重要结局的严重程度，而不仅仅是基于对关节损伤的评估，这一点很重要。从 X 光片上解读的关节损伤并不一定代表所经历的症状。OA 的治疗主要包括药物治疗、手术干预和各种非药物干预。
