Systematic reviews including this primary study

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Systematic review

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Journal Clinical rheumatology
Year 2018
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Osteoarthritis (OA) of the knee is one of the main causes of mobility decline in the elderly. Non-surgical treatments such as administration of supplements to strengthen the joint cartilage matrix have become popular not only for pain relief but also for joint preservation. Glucosamine has been used in many countries based on the increasing evidence of its effectiveness for OA. Although there are many previous studies and systematic reviews, the findings vary and different conclusions have been drawn. We aimed to review recent randomized controlled trials on glucosamine for knee OA to reveal up-to-date findings about this supplement. We also performed a meta-analysis of some of the outcomes to overcome the unsolved bias in each study. Eighteen articles written between 2003 and 2016 were analyzed. Many used visual analogue scale (VAS) pain scores and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), which were assessed in our meta-analysis. We found a marginally favorable effect of glucosamine on VAS pain scores. The effect on knee function, as measured by the WOMAC, was small and not significant. A newly established knee OA scale, the Japanese Knee Osteoarthritis Measure (JKOM), is commonly used in Japan. Although the number of subjects was small, the JKOM meta-analysis indicated that glucosamine is superior to a placebo in alleviating knee OA symptoms. Given this, we concluded that glucosamine has the potential to alleviate knee OA pain. Further studies are needed to evaluate the effect of glucosamine on knee function and joint preservation, as well as to evaluate the combined effect with other components, such as chondroitin.

Systematic review

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Journal Cochrane Database of Systematic Reviews
Year 2015
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Background: 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. Objectives: 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. Search methods: 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. Selection criteria: 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. Data collection and analysis: Two review authors independently performed all title assessments, data extractions, and risk of bias assessments. Main results: 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. 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 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. © 2016 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.