This study tested chondroitin sulfate 800 mg/day (CS) pharmaceutical-grade in the management of symptomatic knee osteoarthritis. It was designed as a prospective, randomised, 6-month, 3-arm, double-blind, double-dummy, placebo and celecoxib (200 mg/day)-controlled trial.  The primary endpoints were changes in pain on a Visual Analogue Scale (VAS) and in the Lequesne Index (LI). Minimal-Clinically Important Improvement (MCII), Patient-Acceptable Symptoms State (PASS) were used as secondary endpoints.

A total of 604 patients, diagnosed according to American College of Rheumalogy (ACR) criteria, were recruited in five European countries and followed for 182 days. CS and celecoxib showed a greater significant reduction in pain and LI than placebo. In the intention-to-treat (ITT) population, pain reduction in VAS at day 182 in the CS group (−42.6 mm) and in celecoxib group (−39.5 mm) was significantly greater than the placebo group (−33.3 mm) (p=0.001 for CS and p=0.009 for celecoxib). No difference observed between CS and celecoxib. Similar trend for the LI, as reduction in this metric in the CS group (−4.7) and celecoxib group (−4.6) was significantly greater than the placebo group (−3.7) (p=0.023 for CS and p=0.015 for celecoxib). Again, no difference was observed between CS and celecoxib. Both secondary endpoints (MCII and PASS) at day 182 improved significantly in the CS and celecoxib groups. All treatments demonstrated excellent safety profiles.
The authors concluded that a 800 mg/day pharmaceutical-grade CS is superior to placebo and similar to celecoxib in reducing pain and improving function over 6 months in symptomatic knee osteoarthritis (OA) patients. This formulation of CS should be considered a first-line treatment in the medical management of knee OA.

In my view, this is a good study with clear and useful results: CS seems to be efficacious and safe. Another recent study confirmed the superiority of CS over celecoxib at reducing cartilage volume loss in knee OA patients.

The current Cochrane review does not yet account for the new data; it concluded cautiously positive: 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.

The call for more high quality trials was justified but has now been answered. In my view, CS can be considered an evidence-based option in the management of OA.

17 Responses to SURPRISE, SURPRISE: some dietary supplements do work! (Chondroitin for OA)

  • Excellent news. As ever – what do we call CAM that has been proven to work? Oh yes. Medicine.

  • Fantastic! So Chondroitin was quackery up to now having had inconclusive systematic reviews in 2007. So now it becomes medicine .
    Try telling that to the millions who have used Chondroitin in effect as a medicine over the last 15 years.

    It only took 10 years for Evidence Based medicine to catch up. WDDTY have over the last 10 years reported the medicinal benefits of Chondroitin and all they have got for it was abuse.

    EB medicine seems to rely on too many poor systematic reviews.

  • I had a look at this paper, albeit a rather hasty one but I dare to say I am underwhelmed. There may of course still exist a specific effect of ingesting “pharmacological grade” chondroitin but everything indicates that if it exists, it is at best meager in magnitude and this trial certainly does not change that impression.
    If I am not mistaken, this trial shows no short term symptomatic or disease modifying effect. A difference in pain score is only apparent at six months and amounts to only about 8.2/100 VAS points. (Table 2) This needs to be evaluated in contrast with the placebo effect of 33.4 point decrease between first and last observations.

    The Lequesne index, a disease severity score, seems to part very slightly (0.7 points; p=0.050) from placebo at three months and only slightly more at six (0.9 points, p=0.023). Even if this is deemed statistically significant, its relevance is doubtful. This may of course well be a true disease modifying effect of the stuff, but is it reproducible and is the difference clinically relevant at all?
    I am afraid these results are not enough to convince me to go and buy a bottle of chondroitin, even one of “pharmacological grade” if that is to be found and not the usual desiccated fish soup powder on offer at most health-stores. I am even less likely to buy a tube of the stuff mixed in a gel intended for external application! Such products are at the moment heavily marketed in my corner of the world and seem to be sold in shiploads.

    • ‘Pharmaceutical grade’ is a made-up marketing term (first used I believe by unctuous (pardon the pun) fish oil manufacturers to get the public to believe theirs was the “real stuff”).
      That such a term is used in this study makes me very dubious.

  • Dr Geir really should start taking a less hasty look at evidence.

  • Just to be clear, having not read the paper, am I right in saying there was really quite a large swing towards regression of clinical signs in the placebo arm with a small additional reduction in both treatment arms?

    I’m not qualified to judge the clinical significance of these reported statistically significant effects, but if they are small then it is definitely concerning that the NSAID does not put-compete the near-placebo chondroitin.

  • Seems like I am not alone in my doubts (see my comment above)

    Harriet Hall has looked at this matter in more detail:

  • I am sure the commenter “Windriven” over at SBM will not mind me copy-pasting his/her salient comment to Dr Hall’s excellent analysis:

    Cochrane has just released a celecoxib for osteoarthritis report (May 22, 2017 epub ahead of print). Its conclusions bear consideration:

    We are highly reserved about results due to pharmaceutical industry involvement and limited data. We were unable to obtain data from three studies, which included 15,539 participants, and classified as awaiting assessment. Current evidence indicates that celecoxib is slightly better than placebo and some tNSAIDs in reducing pain and improving physical function. We are uncertain if harms differ among celecoxib and placebo or tNSAIDs due to risk of bias, low quality evidence for many outcomes, and that some study authors and Pfizer declined to provide data from completed studies with large numbers of participants. To fill the evidence gap, we need to access existing data and new, independent clinical trials to investigate benefits and harms of celecoxib versus tNSAIDs for people with osteoarthritis, with longer follow-up and more direct head-to-head comparisons with other tNSAIDs.

    (emphasis mine) To my amateur eyes, if celecoxib ain’t all that and a bag of chips, and if we are comparing the efficacy of chondroitin versus celecoxib, we seem to be very close to counting angels dancing on a pinhead.

    I agree with Windriven.

  • My doctor got me to try the stuff once. Sorry, not even placebo effect.

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