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To Glucosamine or Not Glucosamine?

S. Terry Canale, MD

I have played tennis against some of the best—in orthopaedics, that is. I have been “aced” by the likes of Crawford, Leach, Wilson, Bigliani, Warner, Herring, Peterson, and Guyton. But today I lost in the first round. I still have the ground strokes, but I just couldn’t move.


S. Terry Canale, MD

My new total hips, my slick defibrillator and pacemaker were yelling, “Go faster, old man. We’re behind you, we’re here to help you move,” but my poor knees with patellofemoral arthritis were screaming, “We can’t take it anymore. If you keep pushing us, we’re going to blow your knee joints up like a balloon.”

I am depressed. I need to take some action and get some pain-free motion like the rest of the nation. After all, this is the AAOS year for a nation in motion, and I don’t want to be left behind.

For years I have drawn a little diagram (graph) for my patients. It shows the progression of severity of arthritis compared to the age of the patient (Fig. 1) and what procedures and medications can be tried—no success guaranteed. The only real guarantee is successful total knee arthroplasty (TKA), and I’m not yet willing to do that.

So what are my options?
I’ve given a lot of hyalgen injections, but with lukewarm success. So I don’t like the idea of being a recipient. I know the pros and cons of steroid injections, and I’m not interested. I have tried over-the-counter and prescription NSAIDs with some success, but symptoms return when you stop the meds. I am a “heart patient” on Coumadin and older than 65 years, so I think (except in a big tournament) I should stay away from drugs like these also.

I think physical therapy has helped with my quadriceps and hamstrings, but it is very easy to aggravate patellofemoral arthritis with the wrong exercise. Also, I’m not much of a “gym rat.”

So what does that leave me to try on my treatment algorithm but glucosamine and chondroitin? Could this be my solution? Am I about to catch up with a nation in motion? Could I beat Crawford one last time with the help of glucosamine and chondroitin? Could I find the fountain of youth and be the tennis champion at the next American Orthopaedic Association annual meeting?

But do they work?
I set out to find the answers about glucosamine and chondroitin. I pulled 166 articles, reviewed 108, and read more than half in their entirety. In summary, the early articles were pessimistic, the European articles were optimistic, and recent U.S. articles were slightly encouraging in certain subsets of patients.

Most articles quoted the “GAIT (Glucosamine/chondroitin Arthritis Intervention Trial) report” funded by the National Institutes of Health in 2006. Basically, the prospective, randomized trial reported that at 2-year follow-up, there was no difference in joint space narrowing among patients with osteoarthritis who received glucosamine chloride alone, took glucosamine chloride with chondroitin sulfate, or took a placebo.

A small subset of patients with Kellgren and Lawrence grade 2 osteoarthritis on radiographs appeared to have the greatest potential for “modification.”

My next step was to find out about this radiographic classification. Grade 2 evidently is “moderate to severe” osteoarthritis, so there is hope (the operative word being hope!).

The majority of the articles can be summarized with three points.

  1. The combination of glucosamine and chrondroitin does not appear to have any more benefit than either one alone, and together they may be less active compared to their individual effects.
  2. In several studies, pain and swelling were decreased (WOMAC scale), but there were just as many studies that found no effect. If there was a beneficial effect, according to most articles, it was at long-term, taking effect at 3, 6, or 9 months. As far as safety goes, the use of glucosamine or chondroitin is equal to a placebo.
  3. Glucosamine sulfate was more effective in most studies than glucosamine chloride as far as lowering pain scores.

The clinical and basic science studies that reported good results used glucosamine sulfate, not glucosamine hydrochloride. Unfortunately, most of the products sold over the counter are glucosamine hydrochloride. Also, some studies suggest chondroitin sulfate alone may be better in reducing pain and swelling than glucosamine alone or a combination of glucosamine and chondroitin.

European clinical studies claim that they have superior results because glucosamine sulfate is used as a “drug” or medicine, while in the United States, glucosamine hydrochloride is used primarily as an over-the-counter supplement. I did learn that it is difficult to obtain glucosamine sulfate in the United States. I looked at 20 different brands and labels of glucosamine and only one was glucosamine sulfate.

I also learned that the recommended dose of glucosamine hydrochloride was 1500 mg/day; for chondroitin sulfate, it’s 1250/mg a day. And I discovered that a lack of standardization in the actual amounts of active ingredients, as well as mislabeling, are quite common in commercially available products (ranging from 50 percent to 100 percent of the amount stated).

Some reputable brands actually state that the product is “manufactured with the highest standard for product quality, including purity and potency.” Generally speaking, the most expensive is usually recommended (for best purity and potency). At my clinic, when asked, we recommend the expensive brands (don’t ask me how that happens).

So there it is—all the research I’m going to do. I’m off to Walgreen’s or Walmart to see the wizard of glucosamine with 20 brands. I know it won’t be easy, so I’ll just pick the one that has 1500 mg of glucosamine sulfate and 1250 mg of chondroitin and is advertised as “triple strength,” and, of course, it must be the most expensive. Perhaps the Walmart greeter can help me—surely he uses glucosamine!

Now what?
I guess by now you must be sitting on pins and needles wanting to know what happened in this non–Institutional Review Board-approved, one-patient research project.

  • At 6 days, “I think it’s helping a little bit.”
  • At 6 weeks, “I really can’t tell any difference. Maybe if I quit taking it, I could.”
  • At 16 weeks, “I’m not sure it’s helping me at all.”
  • At 24 weeks? It’s billed to take that long to have an effect. I’ve not been taking it that long, but perhaps by the time this is published, I will be able to tell you about the results at 24 weeks.

So, what did I learn by going through all this research?

  1. AAOS Now was going to have its annual forum on alternative medicine: “Do glucosamine and chondroitin really work?” We thought we should review the literature, and what you have read is what we found out—inconclusive as far as evidence-based research, very little meaningful research, and most of it inconsistent. So now the forum is going to be on something we can really sink our teeth into—obesity as it relates to orthopaedics.
  2. The “inconclusive” results are just like the AAOS clinical practice guidelines that everyone gets upset over because there are no definite recommendations from the literature. Well, the blame should not be on those formulating the guidelines, but on the lack of creditable research in the literature.
  3. We haven’t even mentioned the expense of alternative medicines such as glucosamine and chondroitin. Are we recommending an expensive drug for our patients, one with no proven benefits, and wasting millions—if not billions—of dollars? On the other hand, if these medications can reduce by just a few the 300,000 TKAs done every year, it may be worth it. I don’t have a “dog in this fight” but I would be willing to spend $35 every couple of months to avoid a TKA.
  4. Finally, one of the main reasons for this editorial is to alert you that Terry Stanton has done an outstanding job of investigative reporting on the “truth about glucosamine and chondroitin.” You should read it in this issue of AAOS Now (see cover) and pass it on to your patients. Because of this article, we may get some push-back from the pharmaceutical industry, but that’s OK; we’ve taken our fish oil and ginseng extract and are ready for them.

P.S. It’s now 24 weeks into my glucosamine and chondroitin routine, and I am ecstatic! I’m playing the best tennis I have played since I was 70! I don’t know whether it’s the medication or not and I don’t care. To heck with Crawford, Herring, and Bigliani—bring on McEnroe and Conners!

AAOS Now
September 2012 Issue
http://www.aaos.org/news/aaosnow/sep12/youraaos1.asp