Glucosamine: where are we now?
The GAIT trial (Glucosamine, chondroitin sulfate, and the two in combination for painful knee osteoarthritis) was recently published in the New England Journal of Medicine. The study was designed to answer the question of wether or not Glucosamine has any benefit in treating patients with osteoarthritis. It compared three treatment groups: Glucosamine, Chondroitin, Glucosamine and Chondroitin, Celebrex only, or placebo. The authors concluded that neither Glucosamine nor Chondroitin helped reduce pain in patients with osteoarthritis of the knee. However, a subgroup of patients with moderate to severe osteoarthritis may experience some benefit fromt he combination of Glucosamine in combination with condroitin.
I heard an interview with Dr. Mark Hochberg, one of the worlds leading authorities in osteoarthritis and editor of a major textbook of Rheumalogy. He discussed his recomendations to patients and views on the subject in light of the GAIT trial results. He stated that since this trial did not conclude there is any benefit from the medication, he is instructing his patients to discontinue the supplement. He then admitted that some of his patients felt worse after discontinuation of the drug and restarted the medication against his advice. I found this response very interesting. If I did the same thing in my practice I feel I would lose a tremendous amount of credibility. I'll elaborate my own views later.
There have been other studies prior to the GAIT trial that yielded mixed results. A study out of Prescott, Az VA Medical Center found that Glucosamine was no better than placebo. In contrast, a study out of Belgium published in the Lancet found that Glucosamine not only helped relieve symptoms of osteoarthritis but also helped delay progression of osteoarthritis by Xray of the knee. A study out of Prague, Czech Republic also found significant symptom relief and delay of progression by Xray while yet another study out of the UK found no benefit when compared to Placebo. The long-awaited study from the NIH (the GAIT tria) was supposed to answer all these questions. In my humble opinion, it raised more questions than answered.
The GAIT study however has been criticized for a number of reasons. First, the reduction of pain in the placebo group was unusually high - about 2/3 of patients in the placebo group found significant relief. Second, the investigators used Glucosamine HCL rather than Glucosamine Sulfate. The latter is more commonly prescribed and it is the prescription form available in Europe through Rottapharm. Third, there seemed to be some benefit in patients with moderate to severe osteoarthritis of the knee when glucosamine was combined with chondroitin. Finally, the results were surprising given that other studies found that patients derived significant pain relief.
So, what should doctors tell their patients? Since the therapy with glucosamine sulfate is very safe, I think a trial is worthwhile. Take glucosamine sulfate (not glucosamine hydrochloride) for 3 months. If you feel better, then continue the therapy. If you do not feel any improvement, then discontinue the product. This approach seems reasonable at least until the reusults of a disease modifying effect are available. That is, if the product prevents progression of arthritis so as to prevent the need for a joint replacement, then we may reconsider.
• N Engl J Med. 2006 Feb 23;354(8):858-60.
Glucosamine, chondroitin sulfate, and the two in combination for painful knee osteoarthritis.
• Arthritis Rheum. 2005 Aug 15;53(4):628-9; author reply 629-30.
Randomized, double-blind, placebo-controlled glucosamine discontinuation trial in knee osteoarthritis.
Arch Intern Med. 2002 Oct 14;162(18):2113-23.
Glucosamine sulfate use and delay of progression of knee osteoarthritis: a 3-year, randomized, placebo-controlled, double-blind study.
Rheumatology (Oxford). 2002 Mar;41(3):279-84.
A randomized, double-blind, placebo-controlled trial of glucosamine sulphate as an analgesic in osteoarthritis of the knee.
Lancet. 2001 Jan 27;357(9252):251-
Long-term effects of glucosamine sulphate on osteoarthritis progression: a randomised, placebo-controlled clinical trial.
• West J Med. 2000 Feb;172(2):95.
Randomized, controlled trial of glucosamine for treating osteoarthritis of the knee.
I heard an interview with Dr. Mark Hochberg, one of the worlds leading authorities in osteoarthritis and editor of a major textbook of Rheumalogy. He discussed his recomendations to patients and views on the subject in light of the GAIT trial results. He stated that since this trial did not conclude there is any benefit from the medication, he is instructing his patients to discontinue the supplement. He then admitted that some of his patients felt worse after discontinuation of the drug and restarted the medication against his advice. I found this response very interesting. If I did the same thing in my practice I feel I would lose a tremendous amount of credibility. I'll elaborate my own views later.
There have been other studies prior to the GAIT trial that yielded mixed results. A study out of Prescott, Az VA Medical Center found that Glucosamine was no better than placebo. In contrast, a study out of Belgium published in the Lancet found that Glucosamine not only helped relieve symptoms of osteoarthritis but also helped delay progression of osteoarthritis by Xray of the knee. A study out of Prague, Czech Republic also found significant symptom relief and delay of progression by Xray while yet another study out of the UK found no benefit when compared to Placebo. The long-awaited study from the NIH (the GAIT tria) was supposed to answer all these questions. In my humble opinion, it raised more questions than answered.
The GAIT study however has been criticized for a number of reasons. First, the reduction of pain in the placebo group was unusually high - about 2/3 of patients in the placebo group found significant relief. Second, the investigators used Glucosamine HCL rather than Glucosamine Sulfate. The latter is more commonly prescribed and it is the prescription form available in Europe through Rottapharm. Third, there seemed to be some benefit in patients with moderate to severe osteoarthritis of the knee when glucosamine was combined with chondroitin. Finally, the results were surprising given that other studies found that patients derived significant pain relief.
So, what should doctors tell their patients? Since the therapy with glucosamine sulfate is very safe, I think a trial is worthwhile. Take glucosamine sulfate (not glucosamine hydrochloride) for 3 months. If you feel better, then continue the therapy. If you do not feel any improvement, then discontinue the product. This approach seems reasonable at least until the reusults of a disease modifying effect are available. That is, if the product prevents progression of arthritis so as to prevent the need for a joint replacement, then we may reconsider.
• N Engl J Med. 2006 Feb 23;354(8):858-60.
Glucosamine, chondroitin sulfate, and the two in combination for painful knee osteoarthritis.
• Arthritis Rheum. 2005 Aug 15;53(4):628-9; author reply 629-30.
Randomized, double-blind, placebo-controlled glucosamine discontinuation trial in knee osteoarthritis.
Arch Intern Med. 2002 Oct 14;162(18):2113-23.
Glucosamine sulfate use and delay of progression of knee osteoarthritis: a 3-year, randomized, placebo-controlled, double-blind study.
Rheumatology (Oxford). 2002 Mar;41(3):279-84.
A randomized, double-blind, placebo-controlled trial of glucosamine sulphate as an analgesic in osteoarthritis of the knee.
Lancet. 2001 Jan 27;357(9252):251-
Long-term effects of glucosamine sulphate on osteoarthritis progression: a randomised, placebo-controlled clinical trial.
• West J Med. 2000 Feb;172(2):95.
Randomized, controlled trial of glucosamine for treating osteoarthritis of the knee.
posted by Ricardo Pocurull at 4:03 PM
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