Singh Jasvinder A, Noorbaloochi Shahrzad, MacDonald Roderick, Maxwell Lara J
Department of Medicine, Birmingham VA Medical Center, Faculty Office Tower 805B, 510 20th Street South, Birmingham, AL, USA, 35294.
Cochrane Database Syst Rev. 2015 Jan 28;1(1):CD005614. doi: 10.1002/14651858.CD005614.pub2.
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 (T(2) = 0.07; I(2) = 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; T(2) = 0.18; I(2) = 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; T(2) = 0.00; I(2) = 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; T(2)= 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); T(2) = 0.33; I(2) = 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 T(2) = 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; T(2) = 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.
AUTHORS' CONCLUSIONS: 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 seeming 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.
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。先前的荟萃分析对软骨素的疗效显示出相互矛盾的结果。此外，随着更多试验的发表，有必要进行系统评价。
评估口服软骨素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、葡萄糖胺或其他“草药”药物）相比治疗骨关节炎的益处和危害。
我们检索了截至2013年11月的七个数据库，包括Cochrane对照试验中央注册库（CENTRAL）、Ovid MEDLINE、CINAHL、EMBASE、科学引文索引（Web of Science）和当前对照试验。我们在美国食品药品监督管理局（FDA）和欧洲药品管理局（EMEA）网站上搜索不良反应。未检索试验注册库。
所有持续时间超过两周的随机或半随机临床试验，研究任何关节患有骨关节炎的成年人，并将软骨素与安慰剂、活性对照（如NSAIDs）或其他“草药”补充剂（如葡萄糖胺）进行比较。
两位综述作者独立进行所有标题评估、数据提取和偏倚风险评估。
纳入了43项随机对照试验，其中4962名参与者接受软骨素治疗，4148名参与者接受安慰剂或其他对照治疗。大多数试验针对膝关节骨关节炎，针对髋关节和手部骨关节炎的试验较少。试验持续时间从1个月到3年不等。在少于6个月的研究中，接受软骨素治疗的参与者在疼痛评分（0 - 100）上比接受安慰剂的参与者在统计学上有显著且具有临床意义的改善，绝对风险差异低10%（95%置信区间（CI），低15%至低6%；需治疗人数（NNT） = 5（95% CI，3至8；n = 8项试验）（证据级别，低；偏倚风险，高）；但试验之间存在高度异质性（T(2) = 0.07；I(2) = 70%，偏倚风险或研究样本量的差异不易解释这种异质性）。在超过6个月的研究中，疼痛的绝对风险差异低9%（95% CI，低18%至0%）；n = 6项试验；T(2) = 0.18；I(2) = 83%），证据级别同样较低。对于西安大略和麦克马斯特大学骨关节炎指数最小临床重要改善（WOMAC MCII疼痛子量表）结果，软骨素组中53/100的患者膝关节疼痛减轻20%，而安慰剂组为47/100，绝对风险差异为6%（95% CI，1%至11%），（RR 1.12，95% CI，1.01至1.24；T(2) = 无需翻译的占位符；I(2) = 0%）（n = 2项试验，1253名参与者；证据级别，高；偏倚风险，低）。在少于6个月的研究中，与安慰剂相比，Lequesne指数（疼痛、功能和残疾的综合指标）的差异在统计学上显著有利于软骨素，绝对风险差异低8%（95% CI，低12%至低5%；T(2)= 0.78；n = 7项试验）（证据级别，中等；偏倚风险，不明确），在临床上也有意义。软骨素组最小关节间隙宽度的减少在统计学上显著小于安慰剂组，相对风险差异少4.7%（95% CI，少1.6%至少7.8%；n = 2项试验）（证据级别，高；偏倚风险，低）。与安慰剂相比，软骨素导致严重不良事件的几率在统计学上显著更低，Peto比值比为0.40（95% CI，0.19至0.82；n = 6项试验）（证据级别，中等）。与安慰剂或其他药物相比，软骨素导致不良事件或因不良事件而退出的数量在统计学上无显著差异。不良事件报告有限，一些研究提供了数据，而其他研究未提供。单独服用软骨素或与葡萄糖胺或其他补充剂联合服用的比较显示，与安慰剂或活性对照相比，疼痛（0 - 100）有统计学上显著的降低，绝对风险差异低了10%（95% CI，低14%至低5%）；NNT = 4（95% CI，3至6）；T(2) = 0.33；I(2) = 91%；n = 17项试验）（证据级别，低）。对于身体功能，软骨素与葡萄糖胺或其他补充剂联合使用与安慰剂或活性对照相比无统计学上显著差异，绝对风险差异低1%（95% CI，低6%至高3%，T(2) = 0.04；n = 5项试验）（证据级别，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，绝对风险差异低8%（95% CI，低12%至低4%；T(2) = 0.12；n = 10项试验）（证据级别，中等）。与安慰剂或活性对照相比，软骨素与葡萄糖胺联合使用在不良事件数量、因不良事件而退出的数量或严重不良事件数量上无统计学上显著差异。当证据仅限于具有充分盲法的研究或使用适当意向性分析（ITT）的研究时，软骨素在疼痛和Lequesne指数方面的有益效果仍然存在。当我们将数据仅限于具有适当分配隐藏或大样本研究（> 200）或无制药资金支持的研究时，这些有益效果并不确定。
对大多质量较低的随机试验的综述表明，在短期研究中，软骨素（单独或与葡萄糖胺联合使用）在改善骨关节炎参与者的疼痛方面优于安慰剂。益处为小到中等，疼痛改善8分（范围0至100），Lequesne指数改善2分（范围0至24），两者在临床上似乎都有意义。这些差异在一些敏感性分析中持续存在，而在其他分析中则不然。与对照相比，软骨素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。软骨素的一些疗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受欢迎程度。
