Differing Preparations of Glucosamine for Osteoarthritis
Differing Preparations of Glucosamine for Osteoarthritis
Objective: To determine the efficacies of different preparations of glucosamine for the treatment of osteoarthritis (OA).
Methods: Systematic searches of the bibliographic databases Medline, Embase, the Cochrane Central Register of Controlled Trials and the Cochrane Database of Systematic Reviews for randomised, double-blind, placebo-controlled trials (RCTs) concerning glucosamine treatment of OA. Effect size (ES) was estimated using Cohen's standardised mean difference. Consistency was evaluated via the I index.
Results: Nineteen trials (3159 patients) contributed to the meta-analysis, revealing a large degree of inconsistency among the trials in terms of pain-reduction outcome: the combined ES in glucosamine sulphate (GS) trials was −0.22 [95% confidence intervals (CI) −0.48, 0.04], I was 82.3%. The combined ES in glucosamine hydrochloride (GH) trials was −0.03 (95% CI −0.14, 0.08), with an absence of heterogeneity. No treatment ES was observed [−0.38 (95% CI −0.99, 0.23)] favouring GS in trials of less than 24 weeks duration and the I remained high (I = 88.5%). No significant treatment ES −0.09 (95% CI −0.21, 0.03) was observed in trials of more than 24 weeks duration compared with placebo, with a heterogeneity of zero. In terms of function-modifying outcomes, GS showed no significant effect on Lequesne Index reduction vs. placebo in trials of less than 24 weeks duration (ES −0.55 (95% CI −1.22, 0.11)) with a high degree of heterogeneity (I = 92.9%). Pooling data from studies with durations of more than 24 weeks presented a significant combined ES of −0.36 (95% CI: −0.56, −0.17) with an absence of heterogeneity. No risk of publication bias could be detected using Egger test.
Conclusions: GH is ineffective for pain reduction in patients with knee OA. GS may have function-modifying effects in patients with knee OA when administered for more than 6 months. However, it showed no pain-reduction benefits after 6 months of therapy.
Osteoarthritis (OA) is the most common form of arthritis, characterised by pain, impaired mobility and degenerative changes in the articular cartilage. Pharmacological therapy for OA consists mainly of analgesics and non-steroidal anti-inflammatory drugs, which may cause serious adverse gastrointestinal and cardiovascular events and do not improve the underlying structural cartilage damage. In patients with symptomatic hip or knee OA, non-steroidal anti-inflammatory drugs should be used at the lowest effective dose and long-term use should be avoided if possible.
Glucosamine is a preferred substrate for the production of aggrecans and other proteoglycans in cartilage. Because of the essential role aggrecans play in cartilage hydrophilicity, compounds that enhance the synthesis of aggrecans may be beneficial in OA. Glucosamine sulphate (GS) has been demonstrated to reduce prostaglandin E2 production in vitro and interfere with nuclear factor κB DNA binding in human chondrocytes and synovial cells. GS and glucosamine hydrochloride (GH) are two large-scale industrialised glucosamine preparations used for the treatment of OA available in Europe and America. GS requires compound stabilisers in the form of sulphate and has 74% purity, whereas GH lacks the sulphate group and has 99% purity. GH at a dosage of 1500 mg is therefore equivalent to a dose of 2608 mg of GS.
There is evidence that glucosamine has both symptomatic and structural effects in OA patients, and clinical trials have suggested that glucosamine therapy decreases OA symptoms compared with placebo. However, the divergent results of previous randomised controlled trials (RCTs) can be attributable to the use of different glucosamine preparations, and different affected joints, methodologies and trial durations etc. Earlier systematic reviews assessed the effect and toxicity of glucosamine irrespective of the preparation types. However, the combination of glucosamine with different salts could have an impact on its effects, and this meta-analysis therefore aimed to investigate the efficacies of different preparations of glucosamine and possible causes of inconsistencies among trials.
We performed a meta-analysis of all available double-blind placebo-controlled RCTs to determine the efficacies of two formulations of glucosamine, GS and GH, and investigated the possible reasons for heterogeneity among trials.
Abstract and Introduction
Abstract
Objective: To determine the efficacies of different preparations of glucosamine for the treatment of osteoarthritis (OA).
Methods: Systematic searches of the bibliographic databases Medline, Embase, the Cochrane Central Register of Controlled Trials and the Cochrane Database of Systematic Reviews for randomised, double-blind, placebo-controlled trials (RCTs) concerning glucosamine treatment of OA. Effect size (ES) was estimated using Cohen's standardised mean difference. Consistency was evaluated via the I index.
Results: Nineteen trials (3159 patients) contributed to the meta-analysis, revealing a large degree of inconsistency among the trials in terms of pain-reduction outcome: the combined ES in glucosamine sulphate (GS) trials was −0.22 [95% confidence intervals (CI) −0.48, 0.04], I was 82.3%. The combined ES in glucosamine hydrochloride (GH) trials was −0.03 (95% CI −0.14, 0.08), with an absence of heterogeneity. No treatment ES was observed [−0.38 (95% CI −0.99, 0.23)] favouring GS in trials of less than 24 weeks duration and the I remained high (I = 88.5%). No significant treatment ES −0.09 (95% CI −0.21, 0.03) was observed in trials of more than 24 weeks duration compared with placebo, with a heterogeneity of zero. In terms of function-modifying outcomes, GS showed no significant effect on Lequesne Index reduction vs. placebo in trials of less than 24 weeks duration (ES −0.55 (95% CI −1.22, 0.11)) with a high degree of heterogeneity (I = 92.9%). Pooling data from studies with durations of more than 24 weeks presented a significant combined ES of −0.36 (95% CI: −0.56, −0.17) with an absence of heterogeneity. No risk of publication bias could be detected using Egger test.
Conclusions: GH is ineffective for pain reduction in patients with knee OA. GS may have function-modifying effects in patients with knee OA when administered for more than 6 months. However, it showed no pain-reduction benefits after 6 months of therapy.
Introduction
Osteoarthritis (OA) is the most common form of arthritis, characterised by pain, impaired mobility and degenerative changes in the articular cartilage. Pharmacological therapy for OA consists mainly of analgesics and non-steroidal anti-inflammatory drugs, which may cause serious adverse gastrointestinal and cardiovascular events and do not improve the underlying structural cartilage damage. In patients with symptomatic hip or knee OA, non-steroidal anti-inflammatory drugs should be used at the lowest effective dose and long-term use should be avoided if possible.
Glucosamine is a preferred substrate for the production of aggrecans and other proteoglycans in cartilage. Because of the essential role aggrecans play in cartilage hydrophilicity, compounds that enhance the synthesis of aggrecans may be beneficial in OA. Glucosamine sulphate (GS) has been demonstrated to reduce prostaglandin E2 production in vitro and interfere with nuclear factor κB DNA binding in human chondrocytes and synovial cells. GS and glucosamine hydrochloride (GH) are two large-scale industrialised glucosamine preparations used for the treatment of OA available in Europe and America. GS requires compound stabilisers in the form of sulphate and has 74% purity, whereas GH lacks the sulphate group and has 99% purity. GH at a dosage of 1500 mg is therefore equivalent to a dose of 2608 mg of GS.
There is evidence that glucosamine has both symptomatic and structural effects in OA patients, and clinical trials have suggested that glucosamine therapy decreases OA symptoms compared with placebo. However, the divergent results of previous randomised controlled trials (RCTs) can be attributable to the use of different glucosamine preparations, and different affected joints, methodologies and trial durations etc. Earlier systematic reviews assessed the effect and toxicity of glucosamine irrespective of the preparation types. However, the combination of glucosamine with different salts could have an impact on its effects, and this meta-analysis therefore aimed to investigate the efficacies of different preparations of glucosamine and possible causes of inconsistencies among trials.
We performed a meta-analysis of all available double-blind placebo-controlled RCTs to determine the efficacies of two formulations of glucosamine, GS and GH, and investigated the possible reasons for heterogeneity among trials.