This review concluded that daily chondroitin (for at least two years) or glucosamine sulphate (for at least three years) may delay the progression of knee osteoarthritis. However, these conclusions may not be reliable given that relevant data were missed, and only a small number of trial were included with small effects and potentially limited applicability to other osteoarthritis sites.

To assess the effects of glucosamine sulphate and chondroitin sulphate on disease progression in patients with osteoarthritis of the knee.

MEDLINE and the Cochrane Central Register of Controlled Trials (CENTRAL) were searched up to July 2008. Search terms were reported. Reference lists of retrieved articles were checked for additional studies. Only papers written in English were eligible for inclusion in the review.

Randomised controlled trials (RCTs) that compared glucosamine sulphate or chondroitin sulphate with a placebo in patients with osteoarthritis of the knee were eligible for inclusion in the review. Eligible studies were required to include joint space narrowing as an outcome variable.

The majority of included trials assessed the effects of chondroitin sulphate (800mg/day) and the remainder assessed the effects of glucosamine sulphate (1,500mg/day). The mean age of participants in the intervention groups ranged from 61.2 to 66 years, and 63.1 to 65.5 years in the control groups, where reported. The body mass index of participants ranged from 25.7 to 27.7kg/m² for the intervention groups and 25.7 to 28.1 kg/m² for the control groups (where reported).

The authors did not state how papers were selected for review.

Trial quality was assessed using the Jadad scale (assessing randomisation, blinding and withdrawals); a quality score between 0 and 5 points was awarded to each trial. The authors also reported whether trials used an intention-to-treat analysis.

The authors did not state how many reviewers performed the validity assessment.

Means and standard deviations (SDs) for the change in knee joint space narrowing from baseline were extracted where available, along with the number of patients with a clinically relevant mean joint space narrowing (>0.5 mm). When data were missing, standard deviation values were imputed from 95% confidence intervals (CIs).

The authors did not state how many reviewers performed the data extraction.

Trials were grouped by intervention and pooled standardised mean differences (SMDs) were calculated for knee joint space narrowing. A pooled effect size of 0.8 was considered to indicate a large effect, 0.5 a moderate effect, and 0.2 a small effect. Pooled odds ratios were calculated using a fixed-effect model, for the incidence of severe narrowing (>0.5 mm). Heterogeneity was assessed using Cochran's Q-statistic and I². I² values of 25, 50 and 75% were referred to indicating low, moderate and high levels of heterogeneity.

A sensitivity analysis was performed to compare the effects of limiting inclusion to trials with short (one year or less) and long (at least two years) follow-up periods.

Publication bias was assessed using funnel plots and the Egger's linear regression test.

Six RCTs were included in review (n=1,502 patients). Three trials were awarded the maximum score for quality (5 points) and two studies scored 3 points; the remaining trial was not awarded a quality score. The drop-out rate within the trials ranged from 8.7 to 45.5%. All but one of the trials used an intention-to-treat analysis. Follow-up periods ranged from one to three years.

Glucosamine sulphate: There was no significant difference between glucosamine sulphate and placebo with respect to knee joint space narrowing over the first year of treatment (two RCTs). However, trials assessing treatment periods of at least three years showed a small to moderate protective effect on minimum joint space narrowing (SMD 0.432, 95% CI 0.235 to 0.628; two RCTs), and a protective effect on severe joint space narrowing (SMD 0.361, 95% CI 0.204 to 0.640; two RCTs).

Chondroitin sulphate: Trials assessing chondroitin sulphate treatment over the first year of treatment (two RCTs) showed no significant difference in knee joint space narrowing in comparison with placebo, but a small significant protective effect was reported after a minimum treatment period of two years (SMD 0.261, 95% CI 0.131 to 0.392; two RCTs) for minimum joint space narrowing (SMD 0.317, 95% CI 0.136 to 0.497; three RCTs) and for mean joint space narrowing (SMD 0.236, 95% CI 0.148 to 0.386; four RCTs).

No significant statistical heterogeneity was detected between the trials with respect to any of the reported analyses.

There was no evidence of publication bias.

Chondroitin sulphate (800mg/day for two years or more) or glucosamine sulphate (1,500mg/day for three years or more) may delay the natural progression of osteoarthritis of the knee.

The authors assessed a clearly defined review question. However, no specific attempts were made to locate unpublished data, so there may be a risk of publication bias; the authors reported tests to assess this risk, but these tests are unlikely to be reliable given the small number of trials included in the review. The restriction to articles written in English also resulted in two trials being excluded from the review, suggesting a risk of language bias. Also, the risk of reviewer error and bias was unclear, as the authors did not report their review methods in detail.

The authors used appropriate criteria to assess the validity of the trials, but only reported the overall quality score and not the score for each separate criterion. A summary of the trial characteristics was presented and the trials appeared to be similar with respect to the characteristics reported. No significant statistical heterogeneity was detected using the Q statistic and I² statistic. The statistical pooling of data appeared appropriate, although the numbers of trials and participants involved were small and the effect sizes often small. The authors acknowledged that their review had a number of limitations, including the limited generalisability of their conclusions to osteoarthritis sites other than the knee, and to other formulations of the interventions including over-the-counter preparations and food supplements.

Overall, the authors' conclusions may not be reliable given that relevant data were missed, and that only a small number of trials, with small effect sizes and potentially limited generalisability to other populations, were included.

Practice: The authors did not state any implications for practice.

Research: The authors stated that further long-term studies on the structural effects of chondroitin and glucosamine sulphate in patients with osteoarthritis of the knee are required.

Not stated.

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.