Chondroitin for osteoarthritis.
Chondroitin for osteoarthritis.
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DOI：
10.1002/14651858.cd005614.pub2
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发表时间：
2015-01-28
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影响因子：
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通讯作者：
Maxwell LJ
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作者：
Singh JA;Noorbaloochi S;MacDonald R;Maxwell LJ
骨关节炎是一种常见的关节疾病，是导致残疾的主要原因之一。软骨素已成为一种新的治疗方法。先前的荟萃分析显示了关于软骨素疗效的相互矛盾的结果。除了发表更多的试验外，还需要进行系统的评价。评估口服软骨素治疗骨关节炎与安慰剂或对照口服药物（包括但不限于非甾体抗炎药（NSAIDs）、镇痛药、阿片类药物、氨基葡萄糖或其他“草药”药物）的利与弊。我们检索了截至2013年11月的7个数据库，包括Cochrane Central Register of Controlled Trials （Central）、Ovid MEDLINE、CINAHL、EMBASE、Science Citation Index （Web of Science）和Current Controlled Trials。我们在美国食品和药物管理局（FDA）和欧洲药品管理局（EMEA）的网站上搜索了不良反应。没有检索试验登记册。所有持续时间超过两周的随机或准随机临床试验，研究患有任何关节骨关节炎的成年人，并将软骨素与安慰剂、非甾体抗炎药等积极对照药物或其他“草药”补充剂（如葡萄糖胺）进行比较。两位综述作者独立完成了所有标题评估、数据提取和偏倚风险评估。43项随机对照试验包括4962名接受软骨素治疗的参与者和4148名接受安慰剂或另一种对照的参与者。大多数试验针对膝关节OA，很少针对髋关节和手部OA。试验时间从1个月到3年不等。在不到6个月的研究中，接受软骨素治疗的参与者获得了具有统计学意义和临床意义的更好的疼痛评分（0-100），绝对风险差降低了10%(95%置信区间（CI），降低了15%至6%；需要治疗的数量(NNT) = 5 （95% CI, 3 ~ 8; n = 8个试验）（证据水平低，偏倚风险高）；但试验之间存在高度异质性（T2 = 0.07; I2 = 70%，这很难用偏倚风险或研究样本量的差异来解释）。在超过6个月的研究中，疼痛的绝对风险差异降低9% (95% CI 18% - 0%)；N = 6个试验；T2 = 0.18；I2 = 83%)，证据水平也很低。对于西安大略大学和麦克马斯特大学骨关节炎指数最小临床重要改善（WOMAC mci疼痛亚量表）结果，软骨素组与安慰剂组相比，膝关节疼痛减少20%的比例为53/100，绝对风险差异为6% (95% CI为1%至11%),(RR为1.12,95% CI为1.01至1.24;T2 = 0.00; I2 = 0%) （n = 2项试验，1253名参与者；证据水平高；偏倚风险低）。在六个月以内的研究中，Lequesne 's指数（疼痛、功能和残疾的综合指数）与安慰剂相比，在统计学上显著有利于软骨素，绝对风险差降低8% （95% CI降低12%至5%；T2= 0.78; n = 7项试验）（证据水平，中等；偏倚风险，不清楚），也具有临床意义。软骨素组最小关节间隙宽度的损失在统计学上显著小于安慰剂组，相对风险差为4.7% （95% CI为1.6% - 7.8%,n = 2个试验）（证据水平高，偏倚风险低）。与安慰剂相比，软骨素与严重不良事件的发生率有统计学意义上显著降低，Peto比值比为0.40 （95% CI 0.19 ~ 0.82; n = 6个试验）（证据水平为中等）。与安慰剂或其他药物相比，软骨素没有导致统计学上显著的不良事件或因不良事件而停药。不良事件的报道是有限的，一些研究提供了数据，而另一些则没有。与安慰剂或主动对照相比，单独服用软骨素或与氨基葡萄糖或其他补充剂联合服用的比较显示，具有统计学意义的疼痛减轻（0-100），绝对风险差降低10% (95% CI降低14%至5%)；NNT = 4 (95% CI 3 ~ 6)；T2 = 0.33；I2 = 91%；N = 17项试验)（证据水平低）。对于身体功能，软骨素联合氨基葡萄糖或其他补充剂与安慰剂或主动对照相比，没有统计学上的显著差异，绝对风险差异降低1% （95% CI降低6%至3%，T2 = 0.04; n = 5个试验）（证据水平，中等）。与安慰剂相比，Lequesne指数的差异在统计学上显著有利于软骨素，绝对风险差降低8% （95% CI，降低12%至4%；T2 = 0.12; n = 10个试验）（证据水平，中等）。与安慰剂或主动对照相比，软骨素联合氨基葡萄糖在不良事件数量、因不良事件而停药或严重不良事件数量方面没有统计学上的显著差异。当证据仅限于充分的盲法研究或使用适当意图治疗（ITT）分析的研究时，软骨素对疼痛和Lequesne指数的有益作用仍然存在。当我们将数据限制在适当分配隐藏或大型研究样本（bbb200）或没有药物资助的研究时，这些有益效果是不确定的。对大多数低质量随机试验的回顾显示，在短期研究中，软骨素（单独或与氨基葡萄糖联合）在改善骨关节炎患者疼痛方面优于安慰剂。获益从小到中等，疼痛改善8分（范围0到100），Lequesne指数改善2分（范围0到24），两者都可能具有临床意义。这些差异在一些敏感性分析中持续存在，而在其他分析中没有。与对照组相比，软骨素组严重不良事件的风险较低。需要更多高质量的研究来探索软骨素在骨关节炎治疗中的作用。与软骨素相关的一些功效和低风险的结合可能解释了它作为非处方补充剂在患者中的流行。
Osteoarthritis, a common joint disorder, is one of the leading causes of disability. Chondroitin has emerged as a new treatment. Previous meta-analyses have shown contradictory results on the efficacy of chondroitin. This, in addition to the publication of more trials, necessitates a systematic review. To evaluate the benefit and harm of oral chondroitin for treating osteoarthritis compared with placebo or a comparator oral medication including, but not limited to, nonsteroidal anti-inflammatory drugs (NSAIDs), analgesics, opioids, and glucosamine or other “herbal” medications. We searched seven databases up to November 2013, including the Cochrane Central Register of Controlled Trials (CENTRAL), Ovid MEDLINE, CINAHL, EMBASE, Science Citation Index (Web of Science) and Current Controlled Trials. We searched the US Food and Drug Administration (FDA) and European Medicines Agency (EMEA) websites for adverse effects. Trial registers were not searched. All randomized or quasi-randomized clinical trials lasting longer than two weeks, studying adults with osteoarthritis in any joint, and comparing chondroitin with placebo, an active control such as NSAIDs, or other “herbal” supplements such as glucosamine. Two review authors independently performed all title assessments, data extractions, and risk of bias assessments. Forty-three randomized controlled trials including 4,962 participants treated with chondroitin and 4,148 participants given placebo or another control were included. The majority of trials were in knee OA, with few in hip and hand OA. Trial duration varied from 1 month to 3 years. Participants treated with chondroitin achieved statistically significantly and clinically meaningful better pain scores (0–100) in studies less than 6 months than those given placebo with an absolute risk difference of 10% lower (95% confidence interval (CI), 15% to 6% lower; number needed to treat (NNT) = 5 (95% CI, 3 to 8; n = 8 trials) (level of evidence, low; risk of bias, high); but there was high heterogeneity between the trials (T2 = 0.07; I2 = 70%, which was not easily explained by differences in risk of bias or study sample size). In studies longer than 6 months, the absolute risk difference for pain was 9% lower (95% CI 18% lower to 0%); n = 6 trials; T2 = 0.18; I2 = 83% ), again with low level of evidence. For the Western Ontario and McMaster Universities Osteoarthritis Index Minimal Clinically Important Improvement (WOMAC MCII Pain subscale) outcome, a reduction in knee pain by 20% was achieved by 53/100 in the chondroitin group versus 47/100 in the placebo group, an absolute risk difference of 6% (95% CI 1% to 11%), (RR 1.12, 95% CI 1.01 to 1.24; T2 = 0.00; I2 = 0%) (n = 2 trials, 1253 participants; level of evidence, high; risk of bias, low). Differences in Lequesne’s index (composite of pain, function and disability) statistically significantly favoured chondroitin as compared with placebo in studies under six months, with an absolute risk difference of 8% lower (95% CI 12% to 5% lower; T2= 0.78; n = 7 trials) (level of evidence, moderate; risk of bias, unclear), also clinically meaningful. Loss of minimum joint space width in the chondroitin group was statistically significantly less than in the placebo group, with a relative risk difference of 4.7% less (95% CI 1.6% to 7.8% less; n = 2 trials) (level of evidence, high; risk of bias, low). Chondroitin was associated with statistically significantly lower odds of serious adverse events compared with placebo with Peto odds ratio of 0.40 (95% CI 0.19 to 0.82; n = 6 trials) (level of evidence, moderate). Chondroitin did not result in statistically significant numbers of adverse events or withdrawals due to adverse events compared with placebo or another drug. Adverse events were reported in a limited fashion, with some studies providing data and others not. Comparisons of chondroitin taken alone or in combination with glucosamine or another supplement showed a statistically significant reduction in pain (0–100) when compared with placebo or an active control, with an absolute risk difference of 10% lower (95% CI 14% to 5% lower); NNT = 4 (95% CI 3 to 6); T2 = 0.33; I2 = 91%; n = 17 trials) (level of evidence, low). For physical function, chondroitin in combination with glucosamine or another supplement showed no statistically significant difference from placebo or an active control, with an absolute risk difference of 1% lower (95% CI 6% lower to 3% higher with T2 = 0.04; n = 5 trials) (level of evidence, moderate). Differences in Lequesne’s index statistically significantly favoured chondroitin as compared with placebo, with an absolute risk difference of 8% lower (95% CI, 12% to 4% lower; T2 = 0.12; n = 10 trials) (level of evidence, moderate). Chondroitin in combination with glucosamine did not result in statistically significant differences in the numbers of adverse events, withdrawals due to adverse events, or in the numbers of serious adverse events compared with placebo or with an active control. The beneficial effects of chondroitin in pain and Lequesne’s index persisted when evidence was limited to studies with adequate blinding or studies that used appropriate intention to treat (ITT) analyses. These beneficial effects were uncertain when we limited data to studies with appropriate allocation concealment or a large study sample (> 200) or to studies without pharmaceutical funding. A review of randomized trials of mostly low quality reveals that chondroitin (alone or in combination with glucosamine) was better than placebo in improving pain in participants with osteoarthritis in short-term studies. The benefit was small to moderate with an 8 point greater improvement in pain (range 0 to 100) and a 2 point greater improvement in Lequesne’s index (range 0 to 24), both likely clinically meaningful. These differences persisted in some sensitivity analyses and not others. Chondroitin had a lower risk of serious adverse events compared with control. More high-quality studies are needed to explore the role of chondroitin in the treatment of osteoarthritis. The combination of some efficacy and low risk associated with chondroitin may explain its popularity among patients as an over-the-counter supplement.