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Meta-Analysis
. 2005 Apr 18;2005(2):CD002946.
doi: 10.1002/14651858.CD002946.pub2.

Glucosamine therapy for treating osteoarthritis

T E Towheed  1 , L Maxwell, T P Anastassiades, B Shea, J Houpt, V Robinson, M C Hochberg, G Wells
Affiliations
Meta-Analysis

Glucosamine therapy for treating osteoarthritis

T E Towheed et al. Cochrane Database Syst Rev. .

Abstract

Background: Osteoarthritis (OA) is the most common form of arthritis, and it is often associated with significant disability and an impaired quality of life.

Objectives: To review all randomized controlled trials (RCTs) evaluating the effectiveness and toxicity of glucosamine in OA.

Search strategy: We searched MEDLINE, PREMEDLINE, EMBASE, AMED, ACP Journal Club, DARE, CDSR, and the CCTR. We also wrote letters to content experts, and hand searched reference lists of identified RCTs and pertinent review articles. All searches were updated in January 2005.

Selection criteria: Relevant studies met the following criteria: 1) RCTs evaluating the effectiveness and safety of glucosamine in OA, 2) Both placebo controlled and comparative studies were eligible, 3) Both single blinded and double blinded studies were eligible.

Data collection and analysis: Data abstraction was performed independently by two investigators and the results were compared for degree of agreement. Gotzsche's method and a validated tool (Jadad 1996) were used to score the quality of the RCTs. Continuous outcome measures were pooled using standardized mean differences (SMD) as the measure of effect size. Dichotomous outcome measures were pooled using relative risk ratios (RR).

Main results: Analysis restricted to eight studies with adequate allocation concealment failed to show benefit of glucosamine for pain and WOMAC function. Collectively, the 20 analyzed RCTs found glucosamine favoured placebo with a 28% (change from baseline) improvement in pain (SMD -0.61, 95% CI -0.95, -0.28) and a 21% (change from baseline) improvement in function using the Lequesne index (SMD -0.51 95% CI -0.96, -0.05). However, the results are not uniformly positive, and the reasons for this remain unexplained. WOMAC pain, function and stiffness outcomes did not reach statistical significance. In the 10 RCTs in which the Rotta preparation of glucosamine was compared to placebo, glucosamine was found to be superior for pain (SMD -1.31, 95% CI -1.99, -0.64) and function using the Lequesne index (SMD -0.51, 95% CI -0.96, -0.05). Pooled results for pain (SMD -0.15, 95% CI -0.35, 0.05) and function using the WOMAC index (SMD 0.03, 95% CI -0.18, 0.25) in those RCTs in which a non-Rotta preparation of glucosamine was compared to placebo did not reach statistical significance. In the four RCTs in which the Rotta preparation of glucosamine was compared to an NSAID, glucosamine was superior in two, and equivalent in two. Two RCTs using the Rotta preparation showed that glucosamine was able to slow radiological progression of OA of the knee over a three year period (SMD 0.24, 95% CI 0.04, 0.43). Glucosamine was as safe as placebo in terms of the number of subjects reporting adverse reactions (RR=0.97, 95% CI, 0.88, 1.08).

Authors' conclusions: This update includes 20 studies with 2570 patients. Pooled results from studies using a non-Rotta preparation or adequate allocation concealment failed to show benefit in pain and WOMAC function while those studies evaluating the Rotta preparation show that glucosamine was superior to placebo in the treatment of pain and functional impairment resulting from symptomatic OA. WOMAC outcomes of pain, stiffness and function did not show a superiority of glucosamine over placebo for both Rotta and non-Rotta preparations of glucosamine. Glucosamine was as safe as placebo.

PubMed Disclaimer

Conflict of interest statement

The current version of the 'Glucosamine for osteoarthritis' review on The Cochrane Library was last revised in 2005.

Dr Tassos Anastassiades submitted patents (Pub. No. US 2002/0045597 A1 and Pub. No. US 6,479,469 B2) for glucosamine type substances in August 2000. The patent protection is for chemically synthesized compounds with substitutions of chain length larger than the naturally occurring acetyl group in glucosamine.

Dr Tanveer Towheed was an invited speaker at the November 2002 ACR meeting. The accredited event, a post‐meeting symposium, was coordinated by the CME department at the Case Western Reserve School of Medicine. Rotta Pharmaceuticals (whose product is glucosamine sulfate) provided an unrestricted educational grant in support of the program. Dr Towheed presented a review of all available published meta‐analyses of various pharmacological therapies for OA. He received a one time honorarium for speaking at this symposium. There is no other association with Rotta Pharmaceuticals, or any other potential conflict of interest.

JB Houpt received an unrestricted grant‐in‐aid of research from Wampole Canada Inc for completion of a trial published in 1999. No industry or other support has been received since.

Figures

1.1
1.1. Analysis
Comparison 1 Glucosamine versus placebo, Outcome 1 Pain.
1.2
1.2. Analysis
Comparison 1 Glucosamine versus placebo, Outcome 2 Lequesne Index.
1.3
1.3. Analysis
Comparison 1 Glucosamine versus placebo, Outcome 3 Lequesne Index.
1.4
1.4. Analysis
Comparison 1 Glucosamine versus placebo, Outcome 4 WOMAC Pain Subscale.
1.5
1.5. Analysis
Comparison 1 Glucosamine versus placebo, Outcome 5 WOMAC Stiffness Subscale.
1.6
1.6. Analysis
Comparison 1 Glucosamine versus placebo, Outcome 6 WOMAC Function Subscale.
1.7
1.7. Analysis
Comparison 1 Glucosamine versus placebo, Outcome 7 WOMAC Total.
1.8
1.8. Analysis
Comparison 1 Glucosamine versus placebo, Outcome 8 Mean Joint Space Width.
1.9
1.9. Analysis
Comparison 1 Glucosamine versus placebo, Outcome 9 Minimum Joint Space Width.
1.10
1.10. Analysis
Comparison 1 Glucosamine versus placebo, Outcome 10 Patient global assessment of disease status score (0‐100mm scale).
1.11
1.11. Analysis
Comparison 1 Glucosamine versus placebo, Outcome 11 Patient global assessment ‐ number responding they are better than at start of trial.
1.12
1.12. Analysis
Comparison 1 Glucosamine versus placebo, Outcome 12 Physician global assessment of disease status score (0‐100).
1.13
1.13. Analysis
Comparison 1 Glucosamine versus placebo, Outcome 13 Physician global assessment of good or excellent response.
1.14
1.14. Analysis
Comparison 1 Glucosamine versus placebo, Outcome 14 Osteoarthritis Research Society International Responder Criteria (OARSI).
1.15
1.15. Analysis
Comparison 1 Glucosamine versus placebo, Outcome 15 Toxicity (Number of Patients Reporting Adverse Events).
1.16
1.16. Analysis
Comparison 1 Glucosamine versus placebo, Outcome 16 Toxicity (Number of Withdrawals due to Adverse Events).
2.1
2.1. Analysis
Comparison 2 Glucosamine versus NSAIDs (piroxicam, ibuprofen, celecoxib), Outcome 1 Pain.
2.2
2.2. Analysis
Comparison 2 Glucosamine versus NSAIDs (piroxicam, ibuprofen, celecoxib), Outcome 2 Lequesne Index.
2.3
2.3. Analysis
Comparison 2 Glucosamine versus NSAIDs (piroxicam, ibuprofen, celecoxib), Outcome 3 Toxicity (Number of Patients Reporting Adverse Events).
2.4
2.4. Analysis
Comparison 2 Glucosamine versus NSAIDs (piroxicam, ibuprofen, celecoxib), Outcome 4 Toxicity (Number of Withdrawals due to Adverse Events).
3.1
3.1. Analysis
Comparison 3 Glucosamine versus placebo (adequate allocation concealment), Outcome 1 Pain.
3.2
3.2. Analysis
Comparison 3 Glucosamine versus placebo (adequate allocation concealment), Outcome 2 Lequesne Index.
3.3
3.3. Analysis
Comparison 3 Glucosamine versus placebo (adequate allocation concealment), Outcome 3 Lequesne Index.
3.4
3.4. Analysis
Comparison 3 Glucosamine versus placebo (adequate allocation concealment), Outcome 4 WOMAC Pain Subscale.
3.5
3.5. Analysis
Comparison 3 Glucosamine versus placebo (adequate allocation concealment), Outcome 5 WOMAC Stiffness Subscale.
3.6
3.6. Analysis
Comparison 3 Glucosamine versus placebo (adequate allocation concealment), Outcome 6 WOMAC Function Subscale.
3.7
3.7. Analysis
Comparison 3 Glucosamine versus placebo (adequate allocation concealment), Outcome 7 WOMAC Total.
3.8
3.8. Analysis
Comparison 3 Glucosamine versus placebo (adequate allocation concealment), Outcome 8 Minimum Joint Space Width.
3.9
3.9. Analysis
Comparison 3 Glucosamine versus placebo (adequate allocation concealment), Outcome 9 Toxicity (Number of Patients Reporting Adverse Events).
3.10
3.10. Analysis
Comparison 3 Glucosamine versus placebo (adequate allocation concealment), Outcome 10 Toxicity (Number of Withdrawals due to Adverse Events).
4.1
4.1. Analysis
Comparison 4 Glucosamine versus placebo (Rotta preparation), Outcome 1 Pain.
4.2
4.2. Analysis
Comparison 4 Glucosamine versus placebo (Rotta preparation), Outcome 2 Lequesne Index.
4.3
4.3. Analysis
Comparison 4 Glucosamine versus placebo (Rotta preparation), Outcome 3 Lequesne Index.
4.4
4.4. Analysis
Comparison 4 Glucosamine versus placebo (Rotta preparation), Outcome 4 WOMAC Pain Subscale.
4.5
4.5. Analysis
Comparison 4 Glucosamine versus placebo (Rotta preparation), Outcome 5 WOMAC Stiffness Subscale.
4.6
4.6. Analysis
Comparison 4 Glucosamine versus placebo (Rotta preparation), Outcome 6 WOMAC Function Subscale.
4.7
4.7. Analysis
Comparison 4 Glucosamine versus placebo (Rotta preparation), Outcome 7 WOMAC Total.
5.1
5.1. Analysis
Comparison 5 Glucosamine versus placebo (non‐Rotta preparation), Outcome 1 Pain.
5.2
5.2. Analysis
Comparison 5 Glucosamine versus placebo (non‐Rotta preparation), Outcome 2 WOMAC Total.
5.3
5.3. Analysis
Comparison 5 Glucosamine versus placebo (non‐Rotta preparation), Outcome 3 WOMAC Pain Subscale.
5.4
5.4. Analysis
Comparison 5 Glucosamine versus placebo (non‐Rotta preparation), Outcome 4 WOMAC Stiffness Subscale.
5.5
5.5. Analysis
Comparison 5 Glucosamine versus placebo (non‐Rotta preparation), Outcome 5 WOMAC Function Subscale.
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