【晨读】骨关节炎药物治疗的选择过程是什么?（四）

 英语晨读 ·

山东省立医院疼痛科英语晨读已经坚持10余年的时间了，每天交班前15分钟都会精选一篇英文文献进行阅读和翻译。一是可以保持工作后的英语阅读习惯，二是可以学习前沿的疼痛相关知识。我们会将晨读内容与大家分享，助力疼痛学习。

本次文献选自Yu S P , Hunter D J . What is the selection process for osteoarthritis pharmacotherapy?[J]. Expert Opinion on Pharmacotherapy, 2020(9):1-5.

The use of exogenous intra-articular viscosupplements is based on the concept that it may restore the viscoelastic properties of the osteoarthritic joint with the added benefit of potential analgesic and anti-inflammatory properties . The main issue with this therapy is that the apparent benefit is seen mainly in trials with a higher risk of bias. There are numerous comparative trials assessing viscosupplementation to that of placebo, corticosteroids, NSAIDS, platelet-richplasma and paracetamol. However, the evidence is conflicting. Viscosupplement have been shown to be superior to placebo, corticosteroids and NSAIDs, in terms of knee pain and function. However, in general, meta-analysis of viscosupplements has shown that the overall effect size of this injection is small and not of clinical importance, and when assessing best-evidence randomized controlled trials, differences between hyaluronic acid and placebo were not observed. In addition to the high cost per injection, there are potential harms ranging from minor side effects including injection site pain, local joint pain and swelling to more serious side effects such as the development of a pseudoseptic reaction, or a flare of crystalline arthritis.

外源性关节内粘补剂的使用是基于这样一种概念，即它可以恢复骨关节炎关节的粘弹性特性，并具有潜在的镇痛和抗炎特性。这种疗法显示明显的益处，其主要问题是试验设计偏倚风险较高。有许多对照试验评估增粘剂与安慰剂、类固醇激素、非甾体抗炎药、PRP和扑热息痛。然而，证据是相互矛盾的。在膝关节疼痛和功能方面，增粘剂已被证明优于安慰剂、皮质类固醇和非甾体抗炎药。增粘剂的荟萃分析表明，这种注射剂的总体效果较小，不具有临床重要性，在最佳证据随机对照试验时，没有观察到透明质酸和安慰剂之间的差异。除了高昂的每次注射费用，还有一些潜在的危害，包括轻微的副作用，包括注射部位疼痛、局部关节疼痛和肿胀，以及更严重的副作用，如假性感染反应，或结晶性关节炎的爆发。

Nutraceuticals are popular with their direct marketing and labeling of the products stating its potential benefits for specific chronic conditions. The use of fish oil, vitamin D, glucosamine, chondroitin sulfate are all discouraged in OA guidelines. There is limited evidence of their efficacy in OA, and glucosamine, the most commonly used supplement is now strongly recommended against by OA guidelines. There are concerning publication biases in glucosamine trials with a trend toward a larger effect size in industry-sponsored trials. Lately, there has been more topical focus toward curcumin, the principal curcuminoid extracted from turmeric root (curcuma longa). Curumin is thought to be an inhibitor of nuclear factor-kappa β (NF- κβ) and may have pain reduction effects in OA. A recent double-blind multi-center, randomized placebo controlled trial of a bio-optimized curcuma longa extract showed a significant decrease in knee OA pain, with positive trends for Patient Global Assessment of Disease Activity and serum sColl2-1, a biomarker of cartilage degradation. The study is of short duration with 150 participants, and further large-scale investigational trials are required before conclusive recommendations can be made for this nutraceutical.

保健品因其直接营销和产品标签说明其对特定慢性疾病的潜在益处而广受欢迎。OA指南都是不鼓励使用鱼油，维生素D，氨基葡萄糖，硫酸软骨素。它们对OA的疗效的证据是有限的，而氨基葡萄糖，最常用的补充剂，现在被OA指南强烈推荐反对使用 。氨基葡萄糖的研究有偏倚，在产业链赞助的试验中，氨基葡萄糖倾向于更大的效应量。最近，从姜黄根中提取的姜黄素越来越受到关注。姜黄素被认为是一种NF -kβ抑制剂),可减少OA疼痛。最近，一项双盲、多中心、随机安慰剂对照试验显示，生物优化的姜黄提取物可显著缓解膝关节OA疼痛，患者疾病活度总体评估和血清scoll2 -1(软骨降解生物标志物)呈积极趋势。该研究是一个有150名参与者的短期研究，需要进一步大规模的研究试验，才能对该营养药物作出结定论的建议。

The limitations of available pharmacotherapy for OA, has led to investigational use of traditional anti-rheumatic medications along with intra-articular 'biological’ or blood-derived therapies. Disease modifying agents for anti-rheumatic drugs such as methotrexate and hydroxychloroquine, along with bisphosphonates, tumor necrosis factor (TNF inhibitors) and IL-1 receptor antagonists are not recommended based on failed clinical trials in OA. Despite commercial availability of platelet-rich plasma and stem cell injections, international OA guidelines strongly oppose the employment of these injections in hip and knee OA due to trial heterogeneity and lack of standardization in preparation and techniques. Highquality investigational trials and cost-effective analysis are required, before further advocation of these therapies.

由于现有药物治疗OA的局限性，导致尝试使用传统抗风湿病药物与关节内注射“生物”制剂或血液来源疗法。基于OA的临床试验失败，不推荐用于抗风湿病药物，如甲氨蝶呤和羟氯喹，以及二膦酸盐、肿瘤坏死因子(TNF抑制剂)和IL-1受体拮抗剂。尽管富血小板血浆和干细胞注射在商业上是可行的，但由于试验的异质性以及在准备和技术上缺乏标准化，国际OA指南强烈反对在髋关节和膝关节OA中使用这些注射。在进一步推广这些疗法之前，需要高质量的调查试验和成本效益分析。