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Effects of glucosamine, chondroitin, or placebo in patients with osteoarthritis of hip or knee: network meta-analysis

BMJ 2010; 341 doi: (Published 16 September 2010) Cite this as: BMJ 2010;341:c4675

Don't count your chickens until they are ALL hatched

Dear Eds

I am no fan of health supplements but I am aware of the increasing
use of Glucosamine and similar preparation promoted for use for
osteoarthritis (OA). There is few good research on the efficacy of
glucosamine and chondroitin in their effectiveness therefore I appreciate
the efforts of the authors (Ref 1) to help differentiate the information
available out there.

However like several meta-analysis and guidelines including those of
American Academy of Orthopaedic Surgeons (Ref 2), the reseachers failed to
consider several current factors in their assessment of these drugs,
specifically glucosamine:

1. Glucosamine comes in 2 different formulation and manufactured
often in conditions not the same as pharmaceutical standards. Higher
quality studies reporting favourable response of glucosamine to knee OA
involves glucosamine sulphate not hydrochloride. It also appears that
Rottapharm is involved in these studies where trials are industry-funded.
Whether or not it is only Rottapharm-patented glucosamine sulphate
formulation that gives better results than other glucosamine formulation
is unclear.

2. While I cannot account for all the guidelines and recommendations
of Glucosamine in the world, I am aware of several prominent groups like
OsteoArthritis Research Society International and Arthritis Foundation
mostly discuss their recommendations of use of glucosamine on knee (and
not hip) osteoarthritis. I believe that the hetergeneity in several meta-
analyses of glucosamine trials may also be due to the group analysis of
knee and hip OA in the attempt to improve the power of the analyses.

3. Some studies have remarkably high placebo effect (60.1% in the
GAIT study: Ref 3) and also complicated by the variation in severity of OA
of participants between trials. It is therefore difficult to conclude if
glucosamine is only beneficial to certain stages of knee OA; in milder OA
the gross fluctuation of symptoms make it too hard to detect a difference
while in advanced OA the symptoms is too severe to modify outcome.

I noted that initial results of LEGS trial (ref 4), which
investigates glucosamine sulphate in knee OA with pain score 4 to 10 on
Visual Analogue Scale, would not be available before October 2011.
Nevertheless in view of the issues with hightlighted above, I do not
believe that we can draw any firm conclusion without the results of this
trial, which addresses all my concerns with the meta-analyses of efficacy
of glucosamine (sulphate) on (knee) osteoarthritis performed so far.

The last egg has not hatched yet. It may very well be the golden
goose you are waiting for, and not a chicken!


1. Wandel S et al; Effects of glucosamine, chondroitin, or placebo in
patients with osteoarthritis of hip or knee: network meta-analysis. BMJ

2. American Academy of Orthopaedic Surgeons Clinical Practice
Guideline on the
Treatment of Osteoarthritis of the Knee (Non-Arthroplasty). Rosemont (IL):
Academy of Orthopaedic Surgeons (AAOS); 2008 URL: Accessed: 2010-09
-17 (Archived by WebCite? at

3. Clegg DO, Reda DJ, Harris CL, Klein MA, O'Dell JR, Hooper MM, et
al. Glucosamine, chondroitin sulfate, and the two in combination for
painful knee osteoarthritis.N Engl J Med 2006;354:795-808

4. Fransen M, Day R, Bridges-Webb C, Edmonds J, Norton R,Woodward M,
et al. The long-term evaluation of glucosamine sulphate study (LEGS).

Competing interests: No competing interests

17 September 2010
Shyan Goh
Orthopaedic Registrar
Lismore Base Hospital NSW Australia