To undertake a mini-review of double-blind randomised controlled trials (RCTs) comparing the effectiveness of oral glucosamine to ibuprofen for the relief of joint pain in osteoarthritis.

MEDLINE (from 1966 to present), EMBASE (from 1980 to present), a database provided by Merck Co. (all dates), AMED (all dates) and the Cochrane Library were searched for relevant articles reported in any language. The search terms were provided in the paper. In addition, the authors examined the reference list of a systematic review that compared glucosamine with placebo.

Study designs of evaluations included in the review

Double-blind RCTs were eligible for inclusion. Any trials that were single-blind were excluded.

Specific interventions included in the review

Comparisons of an oral glucosamine preparation with a standard dose of ibuprofen were eligible for inclusion. Trials that studied glucosamine in sulphate or hydrochloride form were included since the available preparations contain either substance. Studies that assessed intramuscular glucosamine were excluded. Trials that compared glucosamine to any other non-steroidal anti-inflammatory drug or placebo were also excluded, as were trials that examined glucosamine in addition to other analgesics. Trials with a treatment duration of less than 4 weeks were excluded.

The actual interventions compared in the review were 1,500 mg/day glucosamine sulphate and 1,200 mg/day ibuprofen, taken in three divided doses.

Participants included in the review

Osteoarthritis. Studies that assessed adults with a diagnosis of osteoarthritis at any site were eligible for inclusion in the review. All the participants included in the review had either unilateral or bilateral osteoarthritis of the knee.

Outcomes assessed in the review

Studies that included the outcome of pain (described as joint, arthritic or articular pain) measured as perceived improvement or using an ordinal or visual analogue scale to rate pain severity, were eligible for inclusion. Studies examining other outcomes such as joint swelling or adverse effects, but not pain, were excluded. One study used a 9-point scale and one used a 3-point scale. A physician and patient assessment of being 'symptom free' or 'improved' was also undertaken.

How were decisions on the relevance of primary studies made?

The authors do not state how the papers were selected for the review, or how many of the reviewers performed the selection.

The authors do not explicitly state a method for assessing the validity of the included studies. However, they discussed the methodological elements of the randomisation procedure, double-blinding, drop-outs and treatment durations of the included studies. The authors do not state how the papers were assessed for validity, or how many of the reviewers performed the validity assessment.

The authors do not state how the data were extracted for the review, or how many of the reviewers performed the data extraction.

Data on the study and sample size, the study design, length of treatment, treatment regime, the intervention and outcome measures were extracted and presented in tabular format.

How were the studies combined?

A narrative synthesis was undertaken.

How were differences between studies investigated?

The authors combined the results of the two studies and discussed them in relation to the efficacy of the interventions. However, they did not discuss how differences in the samples sizes, the methodological rigour or the year of publication of the studies might have influenced the results obtained.

Two RCTs (n=218) were included.

In both studies, the patients showed statistically-significant improvements in pain whichever drug they took. The pain score at week 4 in the first trial was lower in the glucosamine group than in the ibuprofen group, showing a greater reduction in pain. Pain measured on a 9-point scale fell by 4.8 points in the glucosamine group, compared with 4.3 in the ibuprofen group. However, the difference was not statistically significant (p=0.31). In the second study, at 4 weeks the mean pain scores for both the glucosamine and ibuprofen groups had fallen by 1.1 points in comparison with the baseline scores on a 3-point scale. By 8 weeks, the fall was 1.4 points in the glucosamine group and 1.1 points in the ibuprofen group. The difference was not statistically significant.

Due to the lack of raw data, it was not possible to report the overall proportion of patients whose pain had improved. However, the first trial showed that 84% of the patients considered themselves to be symptom-free or improved at 4 weeks in the glucosamine group, compared with 87% of those in the ibuprofen group. The second trial indicated that all the physicians in both groups in the trial considered the overall efficacy of the treatment to be 'good' or 'fair'; none considered the treatment to be 'insufficient'.

The included studies reported no significant difference between glucosamine and ibuprofen with respect to pain reduction in patients with osteoarthritis. Both were clearly efficacious treatments and glucosamine appeared to be at least as effective as ibuprofen.

The authors addressed a clear review question that was well defined in terms of the interventions, participants, study designs and outcome measures to be assessed. The literature search was adequate, but was restricted to published studies only. This means that relevant unpublished studies may have been missed. The authors did not report a method for assessing the studies for inclusion in the review and, therefore, it is difficult to comment on whether any bias may have been introduced into this process. Likewise, no details of the validity assessment or data extraction were provided. There were minimal details on the characteristics of the primary studies; further participant details, such as disease severity, would have been helpful. The use of a narrative synthesis was appropriate, but the reviewers failed to explore how differences in the sample size or year of publication might have influenced the results obtained.

Overall, this was a poorly conducted and reported review. The authors failed to obtain copies of two studies that fulfilled the inclusion criteria, thus the evidence base reviewed was incomplete. The results of the review should, therefore, be treated with caution.

Practice: The authors state that glucosamine can be used as an alternative to anti-inflammatory drugs and analgesics or as a useful adjunct to standard analgesic therapy, with few short-term adverse effects. However, the patients should be informed that the long-term effects (benefits and harm) are unknown.

Research: The authors did not state any implications for further research.

This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn.