Research - Chondroitin
Chondroitin for osteoarthritis
- Jasvinder A Singh1,*,
- Shahrzad Noorbaloochi2,
- Roderick MacDonald3,
- Lara J Maxwell4
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.
Data collection and analysis
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 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.
Plain Language Summary
We conducted a review of the effects of chondroitin sulfate for people with osteoarthritis. We found 43 studies with 9,110 people after searching for studies up to November 2013. Majority were studies of knee osteoarthritis (few hand, one hip) ranging from 1 month to 3 years. Several studies were funded by makers of chondroitin.
This review shows that in people with osteoarthritis:
- Chondroitin may improve pain slightly in the short-term (less than 6 months);
- Chondroitin improves knee pain by 20% in slightly more people;
- Chondroitin probably improves quality of life slightly as measured by Lequesne's index (combined measure of pain, function, and disability);
- Chondroitin has little or no difference in adverse and serious adverse events versus other agents; and
- Chondroitin slightly slows down the narrowing of joint space on X-rays of the affected joint.
We identified a lot of studies in which unsound methods were used to assess the effects of chondroitin. For some outcomes, there was not enough data. In some studies, whose methodological quality was better, chondroitin showed no improvement in pain and in physical function. Other analyses based on different methodological quality criteria reported improvement in pain and physical functionality when chondroitin was given.
Source : The Cochrane Library
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Chondroitin Eases Pain, Boosts Function in Arthritic Hands
Six months of treatment with chondroitin led to significant improvements in pain and function among patients with osteoarthritis (OA) in their hands, a single-center randomized trial found.
Global hand pain rated on a 100-mm visual analog scale fell by 20 mm for patients taking chondroitin, compared with 11.3 mm for patients receiving placebo, for a between-group difference in change of −8.7 mm (P=0.016), according to Cem Gabay, MD, of University Hospitals of Geneva in Switzerland, and colleagues.
In addition, scores on the 30-point Functional Index for Hand OA decreased by 2.9 points in the chondroitin group and by 0.7 points in the placebo group, giving a between-group difference in change of −2.14 (P=0.008), the researchers reported in the November Arthritis & Rheumatism.
More than half of people older than 60 experience hand OA, with the most commonly involved joints being the distal and proximal interphalangeal, the trapeziometacarpal, and the thumb interphalangeal.
But the therapeutic options are few and data on the efficacy of these therapies are scarce, the authors stated.
Oral nonsteroidal anti-inflammatory drugs (NSAIDs) are helpful for pain relief, but they can cause gastrointestinal side effects and their long-term use is hampered by potentially serious cardiovascular adverse effects.
Topical anti-inflammatory agents also can be somewhat effective, but are not generally convenient for use in a chronic condition.
Acetaminophen is another option, although in the population most affected by hand OA, this drug can have negative effects on blood pressure.
To explore the potential clinical benefits of chondroitin, Gabay and colleagues enrolled 162 patients with severely symptomatic OA, assigning them to six months of daily chondroitin (800 mg) or placebo. Chondrotin is marketed as a dietary supplement in the U.S., but licensed as a prescription OA treatment in much of Europe.
The study drug contained purified chondroitin sulfate derived from fish sources.
Patients all had baseline pain scores of at least 40 mm on the 100-mm visual analog scale and had at least two joints with radiographic evidence of OA.
They were allowed to take rescue acetaminophen in maximum daily doses up to 4 grams.
Their mean age was 63, and two-thirds were women.
Mean pain score at baseline in the target hand was 54 and mean functional score was 11.
The mean number of painful flares during the previous year was 35 in the chondroitin group and 30 in the placebo group.
Patients who had erosive arthritis and involvement of the basal thumb joint had worse functional scores at baseline, but their pain scores were not significantly increased.
These features did not influence treatment outcome, however, on multivariate analysis.
A secondary outcome favoring chondroitin was duration of morning stiffness, which decreased by 4.8 minutes in the active treatment group but increased by 0.3 minutes in the placebo group (between-group difference in change −5.1, P=0.031).
Physician global assessment of efficacy increased during the trial for the chondroitin group, while between-group differences were not seen on acetaminophen use or change in hand grip strength.
Adverse events were reported by 42.5% of the chondroitin patients and by 41.5% of the placebo group.
Two patients in each group experienced serious adverse events, with only one case of abdominal pain in a placebo patient being considered possibly related to treatment.
Three patients in the active treatment group withdrew because of adverse events, as did eight patients in the placebo group.
At the end of the study, tolerability was rated as good or excellent in 96.3% of the active treatment patients and 90.8% of placebo patients.
Chondroitin has not been directly compared with NSAIDs, but the overall magnitude of effect appears to be similar, according to the researchers.
The effect size for pain was "relatively modest," but the improvement in functional scores seen at six months "is indicative of a positive clinical effect of [chondroitin] in this study population," they observed.
They noted that the advantage of anti-inflammatory drugs is prompt relief of symptoms, with the drawback of long-term safety concerns.
"In contrast, the benefits of [chondroitin] appear to take several months to develop, but with hardly any side effects, and this could help reduce the need for long-term [NSAID] therapy in patients with hand OA," they explained.
Limitations of the study included an inadequate numbers of patients to detect differences in some secondary outcomes and in subgroups of patients. Also, a restriction to patients with severe disease.
Source : Medpage Today
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