Check out these comments from Dr.Theodosakis an excellent and re-known arthritis clinician and researcher on the current bogus study - Review of Controversial BMJ (British Medical Journal) article on Glucosamine and Chondroitin- Fake Science

This is the eighth meta-analysis or review article on glucosamine and/or chondroitin. Not sure why it got so much press.

A group of (mostly) Swiss researchers seemed to set out with good intent, to answer the question of whether or not glucosamine and/or chondroitin relieves pain and slows the loss of cartilage. No new patients were studied, this is just a gathering of some (10 out of 58 studies) of the previously published studies on these supplements. The study looks impressive and has enough medical and scientific jargon to seem legitimate.

The trouble is - the study is not legitimate, the researchers made some cardinal mistakes not allowed in a meta-analysis, which I will explain, below. It's such a bizarre interpretation, that it appears to be very suspicious.

Perhaps there are underlying political motivations to try and discourage the British government from covering the cost of these supplements, especially since the supplements (sold as drugs) are covered in other EU countries.

The result is an improper conclusion and improper damage to the supplement's reputation. Glucosamine and Chondroitin remain as the oral therapies with the best risk/benefit ratio of any treatments for osteoarthritis. {You'll enjoy the challenge I propose to those whose opinion differs}.

They somehow made the decision to combine short and long-term information (with different outcomes, mind you) and then said the outcomes were no better than placebo. Sorry- this is nonsense. and then some real science

The rate of decline of joint space width in patients with knee osteoarthritis: a systematic review and meta-analysis of randomized placebo-controlled trials of chondroitin sulfate . Hochberg MC, Zhan M, Langenberg P. University of Maryland School of Medicine, Baltimore, MD, USA. This e-mail address is being protected from spambots. You need JavaScript enabled to view it Abstract BACKGROUND: Chondroitin sulfate has been shown to relieve pain and improve functional limitation in patients with osteoarthritis (OA) of the knee in numerous clinical trials and meta-analyses. Its role as a potential structure-modifying drug for knee OA, however, remains controversial.

OBJECTIVE: To perform a meta-analysis of randomized double-blind placebo-controlled clinical trials to assess the efficacy of chondroitin sulfate as a structure-modifying drug for knee OA. Research design and methods: A Medline search was conducted from 1996 through 2007 and five articles that reported results from three trials were identified; one additional trial was identified through review of presentations at annual rheumatology meetings. There was no evidence of heterogeneity across the trials and results were pooled using a fixed effects meta-analysis.

RESULTS: Pooled results demonstrated a small significant effect of chondroitin sulfate on the reduction in rate of decline in minimum joint space width of 0.07 mm/year (95% CI 0.03, 0.10) that corresponded to an effect size of 0.26 (95% CI 0.14, 0.38) (p < 0.0001). This result was robust in sensitivity analyses. Limitations: The individual studies included in the meta-analysis varied in the number of patients enrolled and the techniques used to acquire knee radiographs and to measure joint space width.

CONCLUSION: These results demonstrate that chondroitin sulfate is effective for reducing the rate of decline in minimum joint space width in patients with knee arthritis. Chondroitin sulfate may have a role as a structure-modifying agent in the management of patients with knee OA.

and some more...

Osteoarthritic patients with high cartilage turnover show increased responsiveness to the cartilage protecting effects of glucosamine sulphate. Christgau S, Henrotin Y, Tankó LB, Rovati LC, Collette J, Bruyere O, Deroisy R, Reginster JY. Nordic Bioscience A/S, Herlev, Denmark. This e-mail address is being protected from spambots. You need JavaScript enabled to view it Abstract

OBJECTIVE: Glucosamine sulphate has been shown in a large double-blind, placebo-controlled clinical trial to prevent structural damage and improve clinical symptoms of osteoarthritis (OA). We investigated whether early response in a newly developed biochemical marker of collagen type II degradation (CTX-II, CartiLaps ELISA) could reflect the long-term preservation of hyaline cartilage.

METHODS: Study subjects comprised 212 knee OA patients participating in a clinical trial of the effects of glucosamine sulphate. Disease symptoms were assessed quarterly by WOMAC scoring and X-ray analysis was performed at baseline and after 3 years. Urine samples were obtained at baseline and after 1, 2 and 3 years for measurement in the CartiLaps assay. The measurements were corrected for creatinine.

RESULTS: At baseline the patients had an average concentration of urinary CTX-II of 222.4 +/- 159.5 ng/mmol creatinine. This was significantly above the CTX-II levels measured in urine samples from 415 healthy controls (169.1 +/- 92.3 ng/mmol, p < 0.0001). There was no significant difference in the CTX-II response in the placebo group and the glucosamine treated group. However, those with high cartilage turnover presented a significant decrease in CTX-II after 12-month glucosamine treatment. Thus, three group with CTX II concentrations above normal average + 1SD decreased 15.5% after 12-month therapy. The 12 months change in CTX-II in OA patients with elevated CTX-II at baseline correlated with the change in average joint space width observed after 36 months (R = 0.43, p < 0.05). Increased baseline levels of CTX-II were associated with a worsening of the WOMAC index (p < 0.01). CONCLUSION: The data indicate that measurement of urinary collagen type II C-telopeptide fragments enables the identification of arthirtis patients with high cartilage turnover who at the same time are most responsive to therapy with structure modifying drugs.

and if you're really in the mood...

STOPP (STudy on Osteoarthritis Progression Prevention): “A new two-year trial with chondroitin 4&6 sulfate (CS)"

Study design according to OA guidance -A. Kahan (France) Clinical results -J.-Y. Reginster (Belgium) Radiological results -E. Vignon (France)

Objective STOPP was a prospective, multicentre, randomised, parallel groups, double blind clinical study comparing 24 month orally administered Chondrosulf® (chondroitin 4&6 sulfate) 800 mg oad vs. placebo in patients with knee osteoarthritis.

Methods A total 600 patients were enrolled (300 patients per group), was targeted in 40 centres from 4 European countries (F, B, CH, A) and the USA. Outpatients of either sex, aged between 45 and 80 years affected by tibio-femoral knee osteoarthritis defined by clinical and radiological criteria were selected. The symptomatic knee (VAS 30 mm) was selected as the target knee since the enrolment for each patient. If both knees were symptomatic, the knee with the narrower joint space was to be selected. If both knees had the same joint space width, the most symptomatic knee was chosen. Patients received Chondrosulf® (chondroitin 4&6 sulfate, CS) 800 mg oral gel (IBSA, Switzerland) vs. placebo, once-a-day for 24 months .

The primary efficacy criteria was the minimal joint space narrowing (JSN) analysed by means of image digitisation. Secondary efficacy criteria were pain using the Huskisson’s VAS. WOMAC algo-functional index, total consumption of paracetamol and authorised NSAIDs. Global efficacy and tolerability were independently assessed by investigators and patients by means of VAS and a semi-quantitative verbal scale respectively.

Treatment compliance and biological markers of arthritis for a sub-group of patients were also assessed. Patients underwent control visits on Day-30, Day 1, Month 1, 3, 6, 9, 12, 15, 18, 21 and 24; the evaluations for a single patient was always carried out by the same investigator. Knee X-rays were taken with the subject in standing and in flex position (Lyon-Schuss) at inclusion visit and after 12, 18 and 24 months. X-rays were analysed in blind as per treatment and sequence at the end of the study according to a technique of image digitisation. A statistical analysis (ITT and PP) was carried out by an external, independent centre.

Results A total of 622 patients meeting the inclusion criteria, 309 in the Chondrosulf® group and 313 in the placebo group, were enrolled by 38 study centres between the years 2000 and 2002. The study groups were balanced at baseline for both demographic and clinical variables, including severity of OA at the target knee.

Ninety-three patients (30.1%) in the CS group and 80 patients (25.6%) in the placebo group did not complete the 2-year treatment course; there were no significant differences between groups in the reasons for withdrawal. Likewise, the number of patients showing good compliance according to the protocol was not significantly different between the groups.

The 312 patients receiving placebo had a progressive JSN with a mean loss ± SE of 0.24 ± 0.03 mm after 2 years. The mean progressive narrowing was of lower extent in the 309 patients receiving CS (0.10 ± 0.03 mm). The ITT analysis of variance for repeated measurements on the last known JSN value showed a statistically significant positive effect of the CS treatment (p<0.01). PP analysis confirmed the results obtained with the ITT analysis. The data from the secondary efficacy parameters confirmed the trend in favour of CS with statistical significance at several end-points. The tolerability was very good in both treatment groups.

Conclusions In this randomised, double-blind, placebo-controlled study CS ( Chondrotin Sulphate) reduced the joint space narrowing in knee OA in comparison to placebo as assessed by radiographic follow-up over 2 years. Long-term treatment with CS appears to delay radiographic progression in patients with knee arthritis. These results are consistent with those already published by others (B.A. Michel et al., Arthritis and Rheumatism 2005; 3(52): 779-786).

and really bad science with lethal consequences for the unsuspecting public-

NIH (NIAMS) GAIT (Glucosamine/Chondroitin Arthritis Intervention Trial) Part 2

Do glucosamine, chondroitin alone or in combination, or Celebrex® slow or stop the loss of cartilage in the knees (as measured by x-rays)? That's was the original intent of this study.

The authors broke their own rules as to what would be allowed for this study to be valid but went ahead anyway and published their suspect results.

That's like saying there's no evidence that Tiger Woods is a better golfer than Dr. Theo. Yes, they did only play four holes, in the dark, and used brooms instead of golf clubs, but Tiger didn't beat Dr. Theo so he's no better. Then the media runs out proclaiming, "Tiger no better than Dr. Theo in golf," in every paper across the country and abroad.

The lead author of the study and the

Why was this study was invalid and should not been able to get published?

Here are the top five reasons:

1) The sample size was too small (only 357 subjects). They required more people to have a statistical significance. They predicted they'd have hundreds more to assess.

2) The study length was too short (two years). In the two best glucosamine x-ray studies (Reginster and Pevelka), most of the change from baseline occurred after year two.

3) The x-ray methodology was not sensitive enough to deliver meaningful measurements. the precision error of the x-ray technique was a whopping 0.16 mm. This is as large as the loss of cartilage in the placebo group over the entire two-year period. This alone invalidated the study. imagine trying to report somebody's weight as 150 pounds when the scale has a error margin of 150 pounds! It's essentially useless.

4) The researchers allowed subjects who had been previously exposed to glucosamine and chondroitin to participate in the study. Since the effect of these supplements are known to stick around for years, people who were assigned to the placebo or Celebrex groups would appear to not lose as much cartilage as they should have lost. For the placebo group, this was proven since the placebo users lost very little cartilage, compared to what was seen in other studies using similar x-ray techniques. No previous study was done using Celebrex for comparison.

5) Those in the placebo group lost less than half the expected amount of joint space width on x-ray. This was incredibly important since each of the treatment groups results were dependent upon direct comparison to the results from those in the placebo group. Therefore, there's no possible way the supplements could have shown a benefit if the placebo users didn't significantly change their joint space from the beginning to the end of the study. This is another reason, even taken alone, that this entire study is invalid.

Introduction:

This study was funded by your tax dollars. GAIT Part 1 was a six-month assessment of pain and function in 1,588 patients with osteoarthritis. The study subjects were randomly assigned to one of five groups: placebo, glucosamine, chondroitin, the combination of glucosamine and chondroitin, or the prescription drug Celebrex.

GAIT 2 was an 18-month continuation of slightly less than half of the number of patients that were involved in GAIT part 1.

Investigators were supposed to continue the outcome measures of GAIT part 1, including pain and function, along with a careful assessment of how much rescue medication (acetaminophen) was needed by participants in each group. GAIT part two was also supposed to measure, using x-rays, the space between the bones in the knees of the participants (commonly referred to as joint space width or JSW). JSW is a surrogate measure of cartilage thickness. The more narrow the space between the bones, the lower the quantity of cartilage exists in the joints.

What did the researchers find?

Those who took glucosamine almost halted their loss of joint space width (they only lost 0.013 mm over two years) but this was not considered to be statistically significant. The other 3 groups were closer to placebo in their JSW loss.

Did the treatment fail or did the study fail?

The study failed. The results shouldn't have even been published. Perhaps this explains the long delay. It appears that the authors manipulated data with a number of statistical adjustments. They refer to this in the article. The study was submitted and subsequently revised.

At least the authors admitted some of the numerous problems each which could have voided the data.

They freely admit this in the discussion section on page 3188 that "the power of the study was limited by a smaller than anticipated sample size, increased variability of the measurement, and a smaller than expected loss in JSW."

Add to this the fact that some users had past exposure to glucosamine and chondroitin (which appears to slow the loss of cartilage for years and probably explains the low level of Joint Space Narrowing in the placebo group), and that the study subjects took supplements three times daily, which causes two problems: lower concentration and effectiveness, and poor compliance (since virtually no one will take six capsules a day, split into three daily doses for a period of two years).

To make matters worse, since there were four different treatment groups and a placebo, the statisticians had to apply a statistical correction factor. This in essence, raised the bar to show a treatment to be statistically significant.

Suspicion surrounding the study

When GAIT part 2 was being designed, there was supposed to be an accounting of the use of rescue medication -- namely acetaminophen. it's important to know if one treatment intervention has the ability to allow for subjects to consume lower quantities of rescue medication as this has substantial public health implications.

Any intervention which could reduce the amount of acetaminophen used during the study might be recommended solely based on this outcome. Acetaminophen, even in low doses, was shown to almost double the incidence of high blood pressure in a major study involving women (The Nurse's health study). Acetaminophen is also the number one cause of intentional and unintentional medication induced liver failure according to the CDC.

It's also strange that a major component to the original study protocol was left out of this publication- the effect of the supplement treatments and Celebrex on pain and function during a two-year period of time. Were the authors trying to hide the fact that Celebrex might not have had any benefit on pain and function for two-year period of time?

Would this affect reimbursement for a drug which costs up to four dollars per day and sometimes requires additional co-medication (acid blockers like Nexium, Prilosec, or Aciphex) costing an extra $2-$6 a day? Why did the financial disclosures of some of the authors change?

For instance, Dan Clegg, MD, the lead investigator for GAIT part 1 disclosed relationships to Pfizer (Celebrex) and McNeil (acetaminophen), the two drugs use in GAIT part I and 2. In GAIT part 2, there was no mention of these associations.

It's one thing for people to disclose any relationships to companies that make the supplements. It's just as important for the authors to disclose if they receive financial benefit, directly or indirectly from companies who are competitors of these supplements, especially since Celebrex and acetaminophen were the two drugs used in the study. This is really important, these authors often have direct control of the data.

It's a very different story when someone, like myself has ties to various supplements and pharmaceutical entities but is just commenting on the study (and does not have the ability to manipulate the data and outcome). The authors did not do the public a service by publishing this data. This was the problem with the first part of GAIT as well.

Rather than just stand up and say that they designed and implemented a study that didn't work and they shouldn't report the results for fear of giving the public improper information, these authors, and the journal in which this article appeared, went ahead and published the study anyway and drew conclusions - which were unfounded.

Unfortunately, the media will pick up on this and relay a faulty message to the public that the supplements didn't work. These articles have already started to appear.

Couldn't agree more with Dr. Theo- glucosamine and chondroitin are wonderful joint nutrients that support healthy cartilage growth.