治疗骨关节炎的主要目标是教导患者对疾病的认识以及控制关节疼痛、僵硬,提高关节功能。治疗包括非药物疗法、药物疗法以及手术治疗。不同的治疗方法可以联合应用,治疗必须要个体化。
在考虑对骨关节炎的治疗方法上,承认安慰剂的疗效作用是重要的。对骨关节炎采用不同治疗干预的随机对照临床试验 meta 分析显示,相对于无治疗对照组,安慰剂能有效减轻疼痛、提高关节功能。[38]Zhang W, Robertson J, Jones AC, et al. The placebo effect and its determinants in osteoarthritis: meta-analysis of randomised controlled trials. Ann Rheum Dis. 2008;67:1716-1723.http://www.ncbi.nlm.nih.gov/pubmed/18541604?tool=bestpractice.com 因此,我们需要辨识出排除安慰剂作用后的循证医学推荐疗法的效果。然而,我们在使用一些治疗方法时常常缺乏有力的循证医学支持,只要这些治疗是安全的,仍可获得安慰剂的疗效。不同类型的安慰剂的效果不同:例如,关节内注射安慰剂和外用安慰剂治疗可能比口服安慰剂疗效更好。[39]Bannuru RR, McAlindon TE, Sullivan MC, et al. Effectiveness and implications of alternative placebo treatments: a systematic review and network meta-analysis of osteoarthritis trials. Ann Intern Med. 2015;163:365-372.http://www.ncbi.nlm.nih.gov/pubmed/26215539?tool=bestpractice.com
非药物疗法
所有患者都应当从非药物疗法开始。其中包括患者教育、向患者说明运动对关节无害、自我管理和运动计划。[40]McKnight PE, Kasle S, Going S, et al. A comparison of strength training, self-management, and the combination for early osteoarthritis of the knee. Arthritis Care Res (Hoboken). 2010;62:45-53.http://www.ncbi.nlm.nih.gov/pubmed/20191490?tool=bestpractice.com[41]Jenkinson CM, Doherty M, Avery AJ, et al. Effects of dietary intervention and quadriceps strengthening exercises on pain and function in overweight people with knee pain: randomised controlled trial. BMJ. 2009;339:b3170.http://www.ncbi.nlm.nih.gov/pubmed/19690345?tool=bestpractice.com[42]Brosseau L, Wells GA, Kenny GP, et al. The implementation of a community-based aerobic walking program for mild to moderate knee osteoarthritis: a knowledge translation randomized controlled trial: part II: clinical outcomes. BMC Public Health. 2012;12:1073.http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3529193/pdf/1471-2458-12-1073.pdfhttp://www.ncbi.nlm.nih.gov/pubmed/23234575?tool=bestpractice.com[43]Tse MM, Vong SK, Tang SK. Motivational interviewing and exercise programme for community-dwelling older persons with chronic pain: a randomised controlled study. J Clin Nurs. 2013;22:1843-1856.http://www.ncbi.nlm.nih.gov/pubmed/23279630?tool=bestpractice.com [
]What are the effects of exercise for people with hip and/or knee osteoarthritis?https://www.cochranelibrary.com/cca/doi/10.1002/cca.2138/full显示答案也推荐物理和职业疗法,及手动运动。[44]Ottawa Methods Group. Ottawa Panel evidence-based clinical practice guidelines for therapeutic exercises and manual therapy in the management of osteoarthritis. Phys Ther. 2005 Sep;85(9):907-71.https://academic.oup.com/ptj/article/85/9/907/2805212http://www.ncbi.nlm.nih.gov/pubmed/16117601?tool=bestpractice.com[45]Jansen MJ, Viechtbauer W, Lenssen AF, et al. Strength training alone, exercise therapy alone, and exercise therapy with passive manual mobilisation each reduce pain and disability in people with knee osteoarthritis: a systematic review. J Physiother. 2011;57:11-20.http://www.ncbi.nlm.nih.gov/pubmed/21402325?tool=bestpractice.com[46]Dziedzic K, Nicholls E, Hill S, et al. Self-management approaches for osteoarthritis in the hand: a 2x2 factorial randomised trial. Ann Rheum Dis. 2015;74:108-118.http://ard.bmj.com/content/74/1/108.longhttp://www.ncbi.nlm.nih.gov/pubmed/24107979?tool=bestpractice.com 股四头肌强化锻炼和单纯减重对控制膝关节骨关节炎疼痛是有效的。[47]Messier SP, Mihalko SL, Legault C, et al. Effects of intensive diet and exercise on knee joint loads, inflammation, and clinical outcomes among overweight and obese adults with knee osteoarthritis: the IDEA randomized clinical trial. JAMA. 2013;310:1263-1273.http://jama.jamanetwork.com/article.aspx?articleid=1741824http://www.ncbi.nlm.nih.gov/pubmed/24065013?tool=bestpractice.com[48]Christensen R, Henriksen M, Leeds AR, et al. Effect of weight maintenance on symptoms of knee osteoarthritis in obese patients: a twelve-month randomized controlled trial. Arthritis Care Res (Hoboken). 2015;67:640-650.http://onlinelibrary.wiley.com/doi/10.1002/acr.22504/fullhttp://www.ncbi.nlm.nih.gov/pubmed/25370359?tool=bestpractice.com 一项 Cochrane 评价表明,运动计划对膝关节骨关节炎具有轻至中度的有益效果。[49]Fransen M, McConnell S, Harmer AR, et al. Exercise for osteoarthritis of the knee. Cochrane Database Syst Rev. 2015;(1):CD004376.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD004376.pub3/fullhttp://www.ncbi.nlm.nih.gov/pubmed/25569281?tool=bestpractice.com [
]Is there randomized controlled trial evidence to support the use of exercise in people with osteoarthritis of the knee?https://cochranelibrary.com/cca/doi/10.1002/cca.713/full显示答案 针对运动对髋关节骨关节炎获益的 meta 分析结果显示,运动对疼痛有适度效果,但是在自我报告的功能方面无改善。[50]Fransen M, McConnell S, Hernandez-Molina G, et al. Does land-based exercise reduce pain and disability associated with hip osteoarthritis? A meta-analysis of randomized controlled trials. Osteoarthritis Cartilage. 2010;18:613-620.http://www.ncbi.nlm.nih.gov/pubmed/20188228?tool=bestpractice.com 一项包含 10 项随机对照临床试验的 Cochrane 综述总结:在髋关节骨关节炎中,运动计划可以减少疼痛并改善躯体功能。[51]Fransen M, McConnell S, Hernandez-Molina G, et al. Exercise for osteoarthritis of the hip. Cochrane Database Syst Rev. 2014;(4):CD007912.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD007912.pub2/fullhttp://www.ncbi.nlm.nih.gov/pubmed/24756895?tool=bestpractice.com 但是,物理治疗对髋关节骨关节炎的益处仍在讨论中。[52]Bennell KL, Egerton T, Martin J, et al. Effect of physical therapy on pain and function in patients with hip osteoarthritis: a randomized clinical trial. JAMA. 2014;311:1987-1997.http://jama.jamanetwork.com/article.aspx?articleid=1872817http://www.ncbi.nlm.nih.gov/pubmed/24846036?tool=bestpractice.com [
]In people with osteoarthritis of the hip, what are the benefits and harms of exercise?https://cochranelibrary.com/cca/doi/10.1002/cca.477/full显示答案
使用支具纠正膝盖脱位很有用,[13]Felson DT. Clinical practice. Osteoarthritis of the knee. N Engl J Med. 2006;354:841-848.http://www.ncbi.nlm.nih.gov/pubmed/16495396?tool=bestpractice.com[53]American College of Rheumatology Subcommittee on Osteoarthritis Guidelines. Recommendations for the medical management of osteoarthritis of the hip and knee: 2000 update. Arthritis Rheum. 2000;43:1905-1915.http://onlinelibrary.wiley.com/doi/10.1002/1529-0131(200009)43:9%3C1905::AID-ANR1%3E3.0.CO;2-P/pdfhttp://www.ncbi.nlm.nih.gov/pubmed/11014340?tool=bestpractice.com 使用膝盖支具对减少髌股关节骨关节炎的疼痛和骨髓病变很有用。[54]Callaghan MJ, Parkes MJ, Hutchinson CE, et al. A randomised trial of a brace for patellofemoral osteoarthritis targeting knee pain and bone marrow lesions. Ann Rheum Dis. 2015;74:1164-1170.http://ard.bmj.com/content/74/6/1164.longhttp://www.ncbi.nlm.nih.gov/pubmed/25596158?tool=bestpractice.com 然而,一项系统评价发现,没有证据表明对内侧膝关节骨关节炎使用矫形器或支架的长期获益,[55]Duivenvoorden T, Brouwer RW, van Raaij TM, et al. Braces and orthoses for treating osteoarthritis of the knee. Cochrane Database Syst Rev. 2015;(3):CD004020.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD004020.pub3/fullhttp://www.ncbi.nlm.nih.gov/pubmed/25773267?tool=bestpractice.com [
]How do braces and orthoses affect outcomes in people being treated for osteoarthritis of the knee?https://cochranelibrary.com/cca/doi/10.1002/cca.817/full显示答案 而另一项系统评价显示,对内侧膝骨关节炎使用膝外翻支架对缓解疼痛具有小至中度的效果。[56]Moyer RF, Birmingham TB, Bryant DM, et al. Valgus bracing for knee osteoarthritis: a meta-analysis of randomized trials. Arthritis Care Res (Hoboken). 2015;67:493-501.http://www.ncbi.nlm.nih.gov/pubmed/25201520?tool=bestpractice.com 建议使用适当的矫形鞋。相对于平底鞋垫,(每天使用并持续使用 12 个月)外侧增高的鞋垫不会改善内侧膝关节骨关节炎症状或减缓结构性疾病的进展。[57]Bennell KL, Bowles KA, Payne C, et al. Lateral wedge insoles for medial knee osteoarthritis: 12 month randomised controlled trial. BMJ. 2011;342:d2912.http://www.bmj.com/content/342/bmj.d2912.longhttp://www.ncbi.nlm.nih.gov/pubmed/21593096?tool=bestpractice.com 另一项研究显示,减荷鞋对内侧膝骨关节炎也没有效。[58]Hinman RS, Wrigley TV, Metcalf BR, et al. Unloading shoes for self-management of knee osteoarthritis: a randomized trial. Ann Intern Med. 2016;165:381-389.http://www.ncbi.nlm.nih.gov/pubmed/27398991?tool=bestpractice.com 同样地,一项 meta 分析总结到,对那些研究进行限定分析,使用中立位鞋垫对减轻疼痛或提高功能的临床作用不明显。[59]Parkes MJ, Maricar N, Lunt M, et al. Lateral wedge insoles as a conservative treatment for pain in patients with medial knee osteoarthritis: a meta-analysis. JAMA. 2013;310:722-730.http://jama.jamanetwork.com/article.aspx?articleid=1730513http://www.ncbi.nlm.nih.gov/pubmed/23989797?tool=bestpractice.com 可考虑使用髌骨支具或髌骨扎贴治疗髌股关节痛。适当用健侧手支撑拐杖行走对于受累的髋关节、膝关节可以减轻疼痛、提高功能。
氨基葡萄糖和硫酸软骨素常作为骨关节炎患者的膳食补充剂;然而,对于它们的使用推荐目前是存在争议的。[60]National Center for Complimentary and Alternative Medicine. The NIH Glucosamine/Chondroitin Arthritis Intervention Trial (GAIT). J Pain Palliat Care Pharmacother. 2008;22:39-43.http://www.ncbi.nlm.nih.gov/pubmed/19062354?tool=bestpractice.com 2010 年的一项 meta 分析表明,膝关节骨关节炎的疼痛或关节间隙狭窄的进展没有出现临床显著的缓解,[61]Wandel S, Jüni P, Tendal B, et al. Effects of glucosamine, chondroitin, or placebo in patients with osteoarthritis of hip or knee: network meta-analysis. BMJ. 2010;341:c4675.http://www.bmj.com/content/341/bmj.c4675.longhttp://www.ncbi.nlm.nih.gov/pubmed/20847017?tool=bestpractice.com 而另一项评价(主要是低质量临床试验)显示,单独使用软骨素或与葡萄糖胺联用在短期缓解膝关节骨关节炎疼痛方面的效果优于比安慰剂。[62]Singh JA, Noorbaloochi S, MacDonald R, et al. Chondroitin for osteoarthritis. Cochrane Database Syst Rev. 2015;(1):CD005614.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD005614.pub2/fullhttp://www.ncbi.nlm.nih.gov/pubmed/25629804?tool=bestpractice.com [
]How does chondroitin affect outcomes in people with osteoarthritis?https://cochranelibrary.com/cca/doi/10.1002/cca.712/full显示答案 益处为小到中等程度,且作者总结说需要高质量研究来探索软骨素在骨性关节炎治疗中的作用。软骨素具有一定的疗效和低风险,这或许是其在患者中受欢迎的原因。[62]Singh JA, Noorbaloochi S, MacDonald R, et al. Chondroitin for osteoarthritis. Cochrane Database Syst Rev. 2015;(1):CD005614.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD005614.pub2/fullhttp://www.ncbi.nlm.nih.gov/pubmed/25629804?tool=bestpractice.com 需要注意的是,这一类补充剂的实际成分和说明之间存在不一致之处,关于此类药物的使用决定应与进行患者讨论。总体来说,GCS 有良好的安全性记录,但会增加一些成本。
针灸对一些患者可能有所帮助。[63]Suarez-Almazor ME, Looney C, Liu Y, et al. A randomized controlled trial of acupuncture for osteoarthritis of the knee: effects of patient-provider communication. Arthritis Care Res (Hoboken). 2010;62:1229-1236.http://www.ncbi.nlm.nih.gov/pubmed/20506122?tool=bestpractice.com[64]Kwon YD, Pittler MH, Ernst E. Acupuncture for peripheral joint osteoarthritis: a systematic review and meta-analysis. Rheumatology (Oxford). 2006;45:1331-1337.http://rheumatology.oxfordjournals.org/content/45/11/1331.longhttp://www.ncbi.nlm.nih.gov/pubmed/16936326?tool=bestpractice.com 其他 meta 分析检验了针灸疗法对治疗骨关节炎的效果。其结果并不一致,但似乎有证据表明针灸疗法对膝关节骨关节炎患者有作用。[65]Cao L, Zhang XL, Gao YS, et al. Needle acupuncture for osteoarthritis of the knee. A systematic review and updated meta-analysis. Saudi Med J. 2012;33:526-532.http://www.ncbi.nlm.nih.gov/pubmed/22588814?tool=bestpractice.com[66]Cao H, Bourchier S, Liu J. Does syndrome differentiation matter? A meta-analysis of randomized controlled trials in Cochrane reviews of acupuncture. Med Acupunct. 2012;24:68-76.http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3579198/http://www.ncbi.nlm.nih.gov/pubmed/24761164?tool=bestpractice.com
一项 meta 分析显示,经皮电神经刺激 (transcutaneous electrical nerve stimulation, TENS) 可能减轻膝关节骨关节炎的疼痛,但作者建议开展更大规模的随机临床试验予以验证。[67]Chen LX, Zhou ZR, Li YL, et al. Transcutaneous electrical nerve stimulation in patients with knee osteoarthritis: evidence from randomized-controlled trials. Clin J Pain. 2016;32:146-154.http://www.ncbi.nlm.nih.gov/pubmed/25803757?tool=bestpractice.com
阶梯式阵痛
非药物治疗在缓解症状不充分时则需要进行药物治疗,尽管对于一些患者根据需要而使用。 局部镇痛药(如辣椒素、复方水杨酸甲酯乳膏、或外用非甾体抗炎药)可作为一线用药治疗。 [
]In adults with chronic musculoskeletal pain, is there randomized controlled trial evidence to support the use of topical NSAIDs?https://cochranelibrary.com/cca/doi/10.1002/cca.1272/full显示答案 另一方面,一项针对局部外用草药治疗骨关节炎治疗的 Cochrane 评价发现,目前此类研究的质量和数量均不足。此外,该评价表明山金车凝胶可能会像局部非甾体抗炎药一样有效地改善症状,但不良事件情况可能更差。这项回顾性研究同样发现辣椒提取物凝胶在试验剂量内不能改善疼痛或功能。[68]Cameron M, Chrubasik S. Topical herbal therapies for treating osteoarthritis. Cochrane Database Syst Rev. 2013;(5):CD010538.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD010538/fullhttp://www.ncbi.nlm.nih.gov/pubmed/23728701?tool=bestpractice.com 如果局部疗法无法控制症状,可以添加对乙酰氨基酚。但是更多可用数据表明对乙酰氨基酚具有潜在不良反应且其疗效有限,因此,在使用对乙酰氨基酚治疗骨关节炎时,应慎重考虑。[69]Machado GC, Maher CG, Ferreira PH, et al. Efficacy and safety of paracetamol for spinal pain and osteoarthritis: systematic review and meta-analysis of randomised placebo controlled trials. BMJ. 2015;350:h1225.http://www.bmj.com/content/350/bmj.h1225.longhttp://www.ncbi.nlm.nih.gov/pubmed/25828856?tool=bestpractice.com 对某些患者来说,NSAID 可能比对乙酰氨基酚更有效;[70]Bannuru RR, Schmid CH, Kent DM, et al. Comparative effectiveness of pharmacologic interventions for knee osteoarthritis: a systematic review and network meta-analysis. Ann Intern Med. 2015;162:46-54.http://www.ncbi.nlm.nih.gov/pubmed/25560713?tool=bestpractice.com 但是,它们有更严重的 GI 和肾毒性。非甾体抗炎药需从最小有效剂量用起,最大程度减少不良反应。与单独应用对乙酰氨基酚相比,布洛芬、对乙酰氨基酚联合应用能适度减轻慢性膝关节疼痛、骨关节炎症状。[71]Doherty M, Hawkey C, Goulder M, et al. A randomised controlled trial of ibuprofen, paracetamol or a combination tablet of ibuprofen/paracetamol in community-derived people with knee pain. Ann Rheum Dis. 2011;70:1534-1541.http://ard.bmj.com/content/70/9/1534.longhttp://www.ncbi.nlm.nih.gov/pubmed/21804100?tool=bestpractice.com 然而,对乙酰氨基酚 3000 mg/天与布洛芬 1200 mg/天 会产生相似程度的血红蛋白降低,联合应用这两种药会产生叠加作用。[71]Doherty M, Hawkey C, Goulder M, et al. A randomised controlled trial of ibuprofen, paracetamol or a combination tablet of ibuprofen/paracetamol in community-derived people with knee pain. Ann Rheum Dis. 2011;70:1534-1541.http://ard.bmj.com/content/70/9/1534.longhttp://www.ncbi.nlm.nih.gov/pubmed/21804100?tool=bestpractice.com
一项 meta 分析研究了各种非甾体抗炎药和对乙酰氨基酚对髋关节和膝关节骨性关节炎疼痛和功能的影响,得出的结论是:由于缺乏有效性,对乙酰氨基酚对治疗髋关节或膝关节骨关节炎缺乏疗效。该研究发现,双氯芬酸最有效,但作者指出,所有药物的安全性都应当予以考虑。[72]da Costa BR, Reichenbach S, Keller N, et al. Effectiveness of non-steroidal anti-inflammatory drugs for the treatment of pain in knee and hip osteoarthritis: a network meta-analysis. Lancet. 2016;387:2093-2105.http://www.ncbi.nlm.nih.gov/pubmed/26997557?tool=bestpractice.com
COX-2 抑制剂被发现具有更小的胃肠道副反应,但它们和非选择性非甾体抗炎药具有相似的肾毒性。[73]Graham DJ, Campen D, Hui R, et al. Risk of acute myocardial infarction and sudden cardiac death in patients treated with cyclo-oxygenase 2 selective and non-selective non-steroidal anti-inflammatory drugs: nested case-control study. Lancet. 2005;365:475-481.http://www.ncbi.nlm.nih.gov/pubmed/15705456?tool=bestpractice.com[74]Maxwell SR, Payne RA, Murray GD, et al. Selectivity of NSAIDs for COX-2 and cardiovascular outcome. Br J Clin Pharmacol. 2006;62:243-245.http://www.ncbi.nlm.nih.gov/pubmed/16842401?tool=bestpractice.com 相较于非甾体抗炎药与有胃肠道保护作用的质子泵抑制剂联用,COX-2 抑制剂在胃肠道症状以及上消化道和心血管不良事件方面不具备优势。[75]Wang X, Tian HJ, Yang HK, et al. Meta-analysis: cyclooxygenase-2 inhibitors are no better than nonselective nonsteroidal anti-inflammatory drugs with proton pump inhibitors in regard to gastrointestinal adverse events in osteoarthritis and rheumatoid arthritis. Eur J Gastroenterol Hepatol. 2011;23:876-880.http://www.ncbi.nlm.nih.gov/pubmed/21900785?tool=bestpractice.com 塞来昔布同非选择性非甾体抗炎药相比对胃肠道副作用有一定的减轻,但在服用低剂量阿司匹林的患者中,没有这个优势。在后者的患者组中,服用非选择性非甾体抗炎药联合质子泵抑制剂或米索前列醇更具成本效益。膝关节骨关节炎的患者,与塞来昔布相比,固定剂量萘普生与埃索美拉唑联合用药有一定的上消化道耐受性,有相近的上消化道不良事件发生率,尽管相比使用塞来昔布的患者,服用萘普生和艾司奥美拉唑的患者报告称出现胃灼热的日子显著减少。[76]Cryer BL, Sostek MB, Fort JG, et al. A fixed-dose combination of naproxen and esomeprazole magnesium has comparable upper gastrointestinal tolerability to celecoxib in patients with osteoarthritis of the knee: results from two randomized, parallel-group, placebo-controlled trials. Ann Med. 2011;43:594-605.http://www.ncbi.nlm.nih.gov/pubmed/22017620?tool=bestpractice.com 鉴于胃肠道出血的风险,应用非甾体抗炎药的患者应考虑胃肠保护的问题。
报告称 COX-2 抑制剂会提高发生心血管事件的风险,而对于许多传统的非甾体抗炎药也是如此。[77]Trelle S, Reichenbach S, Wandel S, et al. Cardiovascular safety of non-steroidal anti-inflammatory drugs: network meta-analysis. BMJ. 2011;342:c7086.http://www.bmj.com/content/342/bmj.c7086.longhttp://www.ncbi.nlm.nih.gov/pubmed/21224324?tool=bestpractice.com 在使用非甾体抗炎药时,一些患者的特征会增加发生脑血管疾病的风险,例如年龄>80 岁、有心血管疾病史、类风湿性关节炎、慢性阻塞性肺病、肾脏疾病和高血压。[78]Solomon DH, Glynn RJ, Rothman KJ, et al. Subgroup analyses to determine cardiovascular risk associated with nonsteroidal antiinflammatory drugs and coxibs in specific patient groups. Arthritis Rheum. 2008;59:1097-1104.http://onlinelibrary.wiley.com/doi/10.1002/art.23911/fullhttp://www.ncbi.nlm.nih.gov/pubmed/18668605?tool=bestpractice.com 一项 meta 分析表明罗非昔布 (rofecoxib)、双氯芬酸和布洛芬会增加心血管疾病风险,而萘普生和塞来昔布则不会。[79]Antman EM, DeMets D, Loscalzo J. Cyclooxygenase inhibition and cardiovascular risk. Circulation. 2005;112:759-770.http://circ.ahajournals.org/content/112/5/759.longhttp://www.ncbi.nlm.nih.gov/pubmed/16061757?tool=bestpractice.com
阿片类药物可在患者的疼痛不能充分控制时使用,或当其他代替药物疗效不充分或存在禁忌时使用。它可单独使用,或联合其他治疗方法使用。曲马多是一种弱阿片类药物,但其对 5-羟色胺和去甲肾上腺素有明显作用,是骨关节炎的替代治疗选择。它对减轻疼痛强度、缓解症状、改善功能方面有一定的效果。患者对曲马多的耐受性一般较好,通常可以联合应用对乙酰氨基酚和/或非甾体抗炎药。[80]Cepeda MS, Camargo F, Zea C, et al. Tramadol for osteoarthritis: a systematic review and metaanalysis. J Rheumatol. 2007;34:543-555.http://www.ncbi.nlm.nih.gov/pubmed/17343302?tool=bestpractice.com 一项 Cochrane 系统评价发现口服或经皮阿片类药物对缓解疼痛具有边际效益,需治人数为 10 例(即需治疗 10 例患者,阿片类药物治疗组比安慰剂组多出现 1 例治疗疼痛有效的患者),但阿片类药物造成的不良反应更多。[81]da Costa BR, Nüesch E, Kasteler R, et al. Oral or transdermal opioids for osteoarthritis of the knee or hip. Cochrane Database Syst Rev. 2014;(9):CD003115.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD003115.pub4/fullhttp://www.ncbi.nlm.nih.gov/pubmed/25229835?tool=bestpractice.com
另一种值得考虑治疗骨关节炎的方法是度洛西汀,其可同时抑制 5-羟色胺和去甲肾上腺素的再摄取。一项系统评价显示,度洛西汀对减轻骨关节炎疼痛中度有效,需治人数为 7 人。[82]Citrome L, Weiss-Citrome A. A systematic review of duloxetine for osteoarthritic pain: what is the number needed to treat, number needed to harm, and likelihood to be helped or harmed? Postgrad Med. 2012;124:83-93.http://www.ncbi.nlm.nih.gov/pubmed/22314118?tool=bestpractice.com 度洛西汀单独使用时能有效减轻膝关节骨关节炎的疼痛和改善其功能,[83]Chappell AS, Desaiah D, Liu-Seifert H, et al. A double-blind, randomized, placebo-controlled study of the efficacy and safety of duloxetine for the treatment of chronic pain due to osteoarthritis of the knee. Pain Pract. 2011;11:33-41.http://www.ncbi.nlm.nih.gov/pubmed/20602715?tool=bestpractice.com 当加用非甾体抗炎药治疗时也有效。[84]Frakes EP, Risser RC, Ball TD, et al. Duloxetine added to oral nonsteroidal anti-inflammatory drugs for treatment of knee pain due to osteoarthritis: results of a randomized, double-blind, placebo-controlled trial. Curr Med Res Opin. 2011;27:2361-2372.http://www.ncbi.nlm.nih.gov/pubmed/22017192?tool=bestpractice.com 度洛西汀最常见的副作用是恶心、乏力、便秘、口干、以及食欲下降,在与曲马多同时使用时,可能会增加 5-羟色胺的影响。度洛西汀对于老年骨关节炎患者的治疗似乎是安全有效的。[85]Abou-Raya S, Abou-Raya A, Helmii M. Duloxetine for the management of pain in older adults with knee osteoarthritis: randomised placebo-controlled trial. Age Ageing. 2012;41:646-652.http://ageing.oxfordjournals.org/content/41/5/646.fullhttp://www.ncbi.nlm.nih.gov/pubmed/22743149?tool=bestpractice.com
常规镇痛后仍出现症状急性加重
关节内皮质类固醇注射和关节内透明质酸是有效的,特别是对膝关节,在骨关节炎急性加重期或当非甾体抗炎药为禁忌或患者不耐受时。一项随机、双盲的比较研究发现,曲安西龙与关节内注射甲基泼尼松龙在膝关节骨关节炎中疗效相似,治疗 24 周时在缓解疼痛和改善功能方面有持续的效果。[86]Lomonte AB, de Morais MG, de Carvalho LO, et al. Efficacy of triamcinolone hexacetonide versus methylprednisolone acetate intraarticular injections in knee osteoarthritis: a randomized, double-blinded, 24-week study. J Rheumatol. 2015;42:1677-1684.http://www.ncbi.nlm.nih.gov/pubmed/26136485?tool=bestpractice.com 一项随机临床试验比较了膝关节骨关节炎中给予低剂量和高剂量关节内注射曲安西龙的疗效,结果显示二者在缓解疼痛、肿胀或功能方面没有差别。[87]Popma JW, Snel FW, Haagsma CJ, et al. Comparison of 2 dosages of intraarticular triamcinolone for the treatment of knee arthritis: results of a 12-week randomized controlled clinical trial. J Rheumatol. 2015;42:1865-1868.http://www.ncbi.nlm.nih.gov/pubmed/26233499?tool=bestpractice.com 这些干预可与患者的定期镇痛和非药物疗法一起使用。膝关节骨关节炎的关节内透明质酸治疗已被进行了大量研究。然而,关于评估其在减轻疼痛效果的研究,结果是相互矛盾的。[88]Lo GH, LaValley M, McAlindon T, et al. Intra-articular hyaluronic acid in treatment of knee osteoarthritis: a meta-analysis. JAMA. 2003;290:3115-3121.http://www.ncbi.nlm.nih.gov/pubmed/14679274?tool=bestpractice.com[89]Blaine T, Moskowitz R, Udell J, et al. Treatment of persistent shoulder pain with sodium hyaluronate: a randomized, controlled trial. A multicenter study. J Bone Joint Surg Am. 2008;90:970-979.http://www.ncbi.nlm.nih.gov/pubmed/18451387?tool=bestpractice.com[90]Lundsgaard C, Dufour N, Fallentin E, et al. Intra-articular sodium hyaluronate 2 mL versus physiological saline 20 mL versus physiological saline 2 mL for painful knee osteoarthritis: a randomized clinical trial. Scand J Rheumatol. 2008;37:142-150.http://www.ncbi.nlm.nih.gov/pubmed/18415773?tool=bestpractice.com[91]Bannuru RR, Natov NS, Obadan IE, et al. Therapeutic trajectory of hyaluronic acid versus corticosteroids in the treatment of knee osteoarthritis: a systematic review and meta-analysis. Arthritis Rheum. 2009;61:1704-1711.http://www.ncbi.nlm.nih.gov/pubmed/19950318?tool=bestpractice.com[92]Chevalier X, Jerosch J, Goupille P, et al. Single, intra-articular treatment with 6 ml hylan G-F 20 in patients with symptomatic primary osteoarthritis of the knee: a randomised, multicentre, double-blind, placebo controlled trial. Ann Rheum Dis. 2010;69:113-119.http://www.ncbi.nlm.nih.gov/pubmed/19304567?tool=bestpractice.com[93]Jørgensen A, Stengaard-Pedersen K, Simonsen O, et al. Intra-articular hyaluronan is without clinical effect in knee osteoarthritis: a multicentre, randomised, placebo-controlled, double-blind study of 337 patients followed for 1 year. Ann Rheum Dis. 2010;69:1097-1102.http://www.ncbi.nlm.nih.gov/pubmed/20447955?tool=bestpractice.com[94]Colen S, Haverkamp D, Mulier M, et al. Hyaluronic acid for the treatment of osteoarthritis in all joints except the knee: what is the current evidence? BioDrugs. 2012;26:101-112.http://www.ncbi.nlm.nih.gov/pubmed/22385405?tool=bestpractice.com[95]Campbell KA, Erickson BJ, Saltzman BM, et al. Is local viscosupplementation injection clinically superior to other therapies in the treatment of osteoarthritis of the knee: a systematic review of overlapping meta-analyses. Arthroscopy. 2015;31:2036-2045.e14.http://www.ncbi.nlm.nih.gov/pubmed/25998016?tool=bestpractice.com 一项 meta 分析评估了关节内注射透明质酸与安慰剂对骨性关节炎治疗的疗效轨迹,结果显示治疗 4 周时关节内注射透明质酸具有显著效果(效应值 0.31,95% 置信区间 0.17,0.45),8 周时疗效到达峰值 (0.46;0.28,0.65),在 24 周时减低到残留效应。[91]Bannuru RR, Natov NS, Obadan IE, et al. Therapeutic trajectory of hyaluronic acid versus corticosteroids in the treatment of knee osteoarthritis: a systematic review and meta-analysis. Arthritis Rheum. 2009;61:1704-1711.http://www.ncbi.nlm.nih.gov/pubmed/19950318?tool=bestpractice.com 一项研究表明,以 6 和 12 个月的间隔期进行关节内注射透明质酸的重复周期治疗可以在 40 个月的周期内具有残存效果,并在最后一次注射治疗后持续 1 年。[96]Navarro-Sarabia F, Coronel P, Collantes E, et al. A 40-month multicentre, randomised placebo-controlled study to assess the efficacy and carry-over effect of repeated intra-articular injections of hyaluronic acid in knee osteoarthritis: the AMELIA project. Ann Rheum Dis. 2011;70:1957-1962.http://ard.bmj.com/content/70/11/1957.longhttp://www.ncbi.nlm.nih.gov/pubmed/21852252?tool=bestpractice.com 中等分子量的透明质酸较小分子量的透明质酸对于骨性关节炎的治疗更有效。[97]Berenbaum F, Grifka J, Cazzaniga S, et al. A randomised, double-blind, controlled trial comparing two intra-articular hyaluronic acid preparations differing by their molecular weight in symptomatic knee osteoarthritis. Ann Rheum Dis. 2012;71:1454-1460.http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3414228/pdf/annrheumdis-2011-200972.pdfhttp://www.ncbi.nlm.nih.gov/pubmed/22294639?tool=bestpractice.com 然而,一些对应用透明质酸治疗骨关节炎的 meta 分析报告称其效果很小。[98]Rutjes AW, Jüni P, da Costa BR, et al. Viscosupplementation for osteoarthritis of the knee: a systematic review and meta-analysis. Ann Intern Med. 2012;157:180-191.http://www.ncbi.nlm.nih.gov/pubmed/22868835?tool=bestpractice.com 这些作者发现有发表偏倚,因为那些阴性结果的临床试验并未发表,并且这些试验的质量整体上较低。在 meta 分析中包含了运用盲法结果评估的 18 项大型临床试验项目,结果显示了与临床无关的效应值。
膝关节穿刺术和注射的动画演示
肩关节穿刺术和注射的动画演示
手术
在使用多种治疗方法后仍然存在疼痛的骨关节炎患者或疼痛需要常规阿片类药物或引起严重功能障碍时,则应当转诊征求骨外科的意见并应当考虑关节置换术。
在适合单侧全膝关节置换术的中至重度膝关节骨关节炎患者中开展了一项随机对照临床试验,发现与单纯非手术治疗相比,全膝关节置换术加上随后的非手术治疗在 12 个月后可显著缓解疼痛,改善功能。然而,全膝关节置换术会导致更严重的不良事件。[101]Skou ST, Roos EM, Laursen MB, et al. A randomized, controlled trial of total knee replacement. N Engl J Med. 2015;373:1597-1606.http://www.nejm.org/doi/full/10.1056/NEJMoa1505467#t=articlehttp://www.ncbi.nlm.nih.gov/pubmed/26488691?tool=bestpractice.com
关节镜手术对膝关节骨关节炎没有效果。[13]Felson DT. Clinical practice. Osteoarthritis of the knee. N Engl J Med. 2006;354:841-848.http://www.ncbi.nlm.nih.gov/pubmed/16495396?tool=bestpractice.com 临床指南不主张在膝关节骨关节炎中使用关节镜手术。该指南所依据的理由是,缺乏表明关节镜手术与保守治疗技术相比可带来更好结局的高质量证据。[102]Siemieniuk RAC, Harris IA, Agoritsas T, et al. Arthroscopic surgery for degenerative knee arthritis and meniscal tears: a clinical practice guideline. BMJ. 2017;357:j1982.http://www.bmj.com/content/357/bmj.j1982http://www.ncbi.nlm.nih.gov/pubmed/28490431?tool=bestpractice.com
BMJ Rapid Recommendations: arthroscopic surgery for degenerative knee arthritis and meniscal tears
[Figure caption and citation for the preceding image starts]: BMJ 快速建议:使用关节镜手术治疗退行性膝关节炎和半月板撕裂Siemieniuk RAC, et al. BMJ. 2017;357:j1982 [Citation ends].
MAGICapp: recommendations, evidence summaries and consultation decision aids
有低到中等质量的证据显示在关节置换前进行术前锻炼可减轻髋或膝关节骨关节炎患者的疼痛,并可提高髋关节置换术后的活动功能。[103]Wallis JA, Taylor NF. Pre-operative interventions (non-surgical and non-pharmacological) for patients with hip or knee osteoarthritis awaiting joint replacement surgery - a systematic review and meta-analysis. Osteoarthritis Cartilage. 2011;19:1381-1395.http://www.ncbi.nlm.nih.gov/pubmed/21959097?tool=bestpractice.com
有数据表明,在全髋关节置换术之前 3 个月内行髋关节内注射皮质类固醇可增加术后假体周围感染。[104]Schairer WW, Nwachukwu BU, Mayman DJ, et al. Preoperative hip injections increase the rate of periprosthetic infection after total hip arthroplasty. J Arthroplasty. 2016;31(suppl):S166-S169.http://www.ncbi.nlm.nih.gov/pubmed/27221820?tool=bestpractice.com[105]Werner BC, Cancienne JM, Browne JA. The timing of total hip arthroplasty after intraarticular hip injection affects postoperative infection risk. J Arthroplasty. 2016;31:820-823.http://www.ncbi.nlm.nih.gov/pubmed/26803711?tool=bestpractice.com 许多骨外科医生建议在关节内注射皮质类固醇后,将关节置换术至少推迟 3 个月。
基于一项随机对照临床试验的结果,半月板部分切除术对具有膝骨关节炎的半月板撕裂不起作用。[106]Katz JN, Brophy RH, Chaisson CE, et al. Surgery versus physical therapy for a meniscal tear and osteoarthritis. N Engl J Med. 2013;368:1675-1684.http://www.nejm.org/doi/full/10.1056/NEJMoa1301408#t=articlehttp://www.ncbi.nlm.nih.gov/pubmed/23506518?tool=bestpractice.com