Am Fam Physician. 2006 Apr 1;73(7):1189-1191.
This clinical content conforms to AAFP criteria for evidence-based continuing medical education (EB CME). EB CME is clinical content presented with practice recommendations supported by evidence that has been reviewed systematically by an AAFP-approved source. The practice recommendations in this activity are available online at http://www.cochrane.org/cochrane/revabstr/AB002946.htm.
A 75-year-old obese woman presents with chronic, severe knee pain from osteoarthritis. She would like to know whether glucosamine sulfate therapy is beneficial.
Is glucosamine sulfate safe and effective for osteoarthritis?
This review1 shows that, compared with placebo, glucosamine sulfate produces a moderate, clinically significant reduction in pain and improvement in function for patients with osteoarthritis. However, study results were not consistent. Most studies in the review used preparations of glucosamine sulfate marketed in Europe by Rotta pharmaceutical company. Subgroup analysis showed that the Rotta preparation had benefit over placebo, whereas non-Rotta preparations did not. Glucosamine does not cause more side effects than placebo.1
Osteoarthritis is the most common arthritis, affecting an estimated 12.1 percent of Americans 25 years and older.1 Therapy includes nonpharmacologic interventions such as weight loss, physical and occupational therapy, and surgery. Medication options include acetaminophen, nonsteroidal anti-inflammatory drugs (NSAIDs), intra-articular injections, opiates, and glucosamine sulfate.2 Glucosamine exists naturally in the body as a building block of cartilage.
This review1 is an update of a Cochrane review published in 2000.3 That review of 16 studies (with a total of 2,029 patients) demonstrated that patients who took 1,500 mg of glucosamine sulfate per day for six weeks had a 60 percent improvement from baseline in pain and a 33 percent improvement in function.3 The update,1 which included only the higher quality studies and eight new studies (2,570 patients), showed less consistent and somewhat less favorable results regarding improvement in pain and function with use of glucosamine sulfate for two to three months.1
The Rotta pharmaceutical company sponsored 65 percent of the studies in the updated review. Studies of the Rotta prescription preparation revealed significant improvements over placebo in pain and in the Lequesne function index, but not in the WOMAC pain, stiffness, and function indices. Non-Rotta preparations showed no benefit over placebo in any of the three outcome measures. Because glucosamine sulfate is not a prescription drug in North America, it is not regulated; therefore, the purity and content can vary greatly.4,5 One study4 of glucosamine and chondroitin supplements showed that label claims differed from the actual content by up to 115 percent. The Rotta pharmaceutical company brand is available in the United States and by prescription in European countries.
Two studies of the radiologic progression of osteoarthritis found that this was slowed by glucosamine over a three-year period. However, the clinical significance of this finding remains uncertain. The authors did not compare the effects of glucosamine on patients with osteoarthritis of different levels of severity and duration, two factors that might affect response to glucosamine.
The safety profile of glucosamine is superior to that of NSAIDs and similar to placebo. In one study,6 88 percent of patients had no adverse effects; in the remaining patients, the majority of side effects were gastrointestinal and resolved on discontinuation of glucosamine. Concerns have been raised about whether glucosamine causes abnormal glucose metabolism, asthma, hypersensitivity, or arteriosclerosis; there is no evidence to support these concerns.
Background. Osteoarthritis is the most common form of arthritis, and it often is 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 osteoarthritis.
Search Strategy. The authors1 searched MEDLINE, PREMEDLINE, EMBASE, AMED, ACP Journal Club, DARE, the Cochrane Database of Systematic Reviews, and the Cochrane Controlled Trials Register. They 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 osteoarthritis; (2) placebo-controlled or comparative studies; (3) single-blinded or double-blinded studies.
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 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 (RRs).
Primary Results. Analysis restricted to eight studies with adequate allocation concealment failed to show benefit of glucosamine for pain and WOMAC function. [WOMAC is a validated health status questionnaire.] Collectively, the 20 analyzed RCTs found glucosamine favored placebo with a 28 percent (change from baseline) improvement in pain (SMD −0.61; 95% confidence interval [CI], −0.95 to −0.28) and a 21 percent (change from baseline) improvement in function using the Lequesne index (SMD −0.51; 95% CI, −0.96 to −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 with placebo, glucosamine was found to be superior for pain (SMD −1.31; 95% CI, −1.99 to −0.64) and function using the Lequesne index (SMD −0.51; 95% CI, −0.96 to −0.05). Pooled results for pain (SMD −0.15; 95% CI, −0.35 to 0.05) and function using the WOMAC index (SMD 0.03; 95% CI, −0.18 to 0.25) in those RCTs in which a non-Rotta preparation of glucosamine was compared with placebo did not reach statistical significance. In the four RCTs in which the Rotta preparation of glucosamine was compared with an NSAID, glucosamine was superior in two and equivalent in two. Two RCTs using the Rotta preparation showed that glucosamine was able to slow radiologic progression of osteoarthritis of the knee over a three-year period (SMD 0.24; 95% CI, 0.04 to 0.43).
Glucosamine was as safe as placebo in terms of the number of participants reporting adverse reactions (RR = 0.97; 95% CI, 0.88 to 1.08).
Reviewers’ Conclusions. This update includes 20 studies with 2,570 patients. Pooled results from studies using a non-Rotta preparation or adequate allocation concealment failed to show benefit in pain and WOMAC function, whereas those studies evaluating the Rotta preparation showed that glucosamine was superior to placebo in the treatment of pain and functional impairment resulting from symptomatic osteoarthritis. WOMAC outcomes of pain, stiffness, and function did not show a superiority of glucosamine over placebo for Rotta or non-Rotta preparations of glucosamine. Glucosamine was as safe as placebo.
These summaries have been derived from Cochrane reviews published in the Cochrane Database of SystematicReviews in the Cochrane Library. Their content has, as far as possible, been checked with the authors of the originalreviews, but the summaries should not be regarded as an official product of the Cochrane Collaboration; minorediting changes have been made to the text (http://www.cochrane.org).
JASMINE CHEN GATTI, M.D., is inpatient hospice medical director at Holy Cross Hospital Home Care and Hospice in Silver Spring, Md., where she is also a family practitioner and geriatrician. She completed a combined fellowship in Australasian Cochrane Collaboration and Medical Education at the Australasian Cochrane Centre, Adelaide, Australia.
Address correspondence to Jasmine Chen Gatti, M.D., Holy Cross Hospital Home Care and Hospice, 11800 Tech Rd., #240, Silver Spring, MD 20910 (e-mail: firstname.lastname@example.org). Reprints are not available from the author.
1. Towheed TE, Maxwell L, Anastassiades TP, Shea B, Houpt J, Robinson V, et al. Glucosamine therapy for treating osteoarthritis. Cochrane Database Syst Rev. 2005;(2):CD002946.
2. Recommendations for the medical management of osteoarthritis of the hip and knee: 2000 update. American College of Rheumatology Subcommittee on Osteoarthritis Guidelines. Arthritis Rheum. 2000;43:1905–15.
3. Towheed TE, Anastassiades TP, Shea B, Houpt J, Welch V, Hochberg MC. Glucosamine therapy for treating osteoarthritis. Cochrane Database Syst Rev. 2000;(2):CD002946.
4. Adebowale AO, Cox DS, Liang Z, Eddington ND. Analysis of glucosamine and chondroitin sulfate content in marketed products and the caco–2 permeability of chondroitin sulfate raw materials. J Am Nutraceutical Assoc. 2000;3:37–44.
5. Russell AS, Aghazadeh-Habashi A, Jamali F. Active ingredient consistency of commercially available glucosamine sulfate products. J Rheumatol. 2002;29:2407–9.
6. Tapadinhas MJ, Rivera IC, Bignamini AA. Oral glucosamine sulphate in the management of arthrosis: report on a multi-centre open investigation in Portugal. Pharmatherapeutica. 1982;3:157–68.
The Cochrane Abstract is a summary of a review from the Cochrane Library. It is accompanied by an interpretation that will help clinicians put evidence into practice. Jasmine Chen Gatti, M.D., presents a clinical scenario and question based on the Cochrane Abstract, followed by an evidence-based answer and a full critique of the review.
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