A Cochrane review [Abstract] 1 included 25 studies with a total of 4 963 subjects (mean age 60.7 years; 69% female). The years of publication (or reporting date) range from 1980 to 2008. A majority of the RCTs (14/25) had some form of relationship with Rotta Pharm, an Italian pharmaceutical manufacturer of glucosamine. Analysis restricted to 11 studies with adequate allocation concealment failed to show benefit of glucosamine for pain and WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index) function; however, it was found to be better than placebo using the Lequesne index (SMD -0.54, 95% CI -0.96 to -0.12). Collectively, the 25 analyzed RCTs favoured glucosamine over placebo with a 22% (change from baseline) improvement in pain (SMD -0.47, 95% CI -0.72 to -0.23) and a 11% (change from baseline) improvement in function using the Lequesne index (SMD -0.47, 95% CI -0.82 to -0.12). 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. Glucosamine was as safe as placebo in terms of the number of subjects reporting adverse reactions (RR 0.99, 95% CI 0.91 to 1.07).
In the RCTs in which the Rotta preparation of glucosamine was compared to placebo, glucosamine was found to be superior for pain (SMD -1.11, 95% CI -1.66 to -0.57; 8 studies) and function using the Lequesne index (SMD -0.47, 95% CI -0.82 to -0.12; 5 studies). Pooled results for pain (SMD -0.05, 95% CI -0.15 to 0.05) and function using the WOMAC index (SMD -0.01, 95% CI -0.13 to 0.10) in those RCTs in which a non-Rotta preparation of glucosamine was compared to placebo did not reach statistical significance. 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 (MD 0.32, 95% CI 0.05 to 0.58).
A network meta-analysis including 10 studies with a total of 3803 subjects with osteoarthritis of the knee or hip was abstracted in DARE. 5 studies (n=1104) compared glucosamine sulphate with placebo. In another placebo controlled trial (n=205), the investigators were forced to change from glucosamine sulphate to glucosamine hydrochloride after 80% of the patients had been treated with glucosamine sulphate because the manufacturer of glucosamine sulphate declined to supply matching placebos. One study (n=1265) compared glucosamine hydrochloride, chondroitin sulphate, and their combination with placebo. On a 10 cm visual analogue scale the overall difference in pain intensity compared with placebo was -0.4 cm (95% credible interval -0.7 to -0.1 cm) for glucosamine, and -0.5 cm (-0.9 to 0.0 cm) for the combination of glucosamine hydrochloride and chondroitin sulphate. Industry independent trials showed smaller effects than commercially funded trials (P=0.02 for interaction). There were no statistically significant differences in changes in minimal joint space narrowing; the difference was -0.2 mm (−0.3 to 0.0 mm) in favour of glucosamine. There were no statistically significant differences in the number of adverse events, and no differences for patient withdrawal or drop-out due to adverse events.
Comment: The quality of evidence is downgraded by inconsistency of results, study limitations and possible publication bias (most of the positive results come from studies done with one manufacturer´s preparation).
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