OBJECTIVES: To compare the efficacies of oral glucosamine, chondroitin, the combination of glucosamine and chondroitin, acetaminophen and celecoxib on the treatment of knee and/or hip osteoarthritis.
METHODS: We searched electronic databases including PubMed, Embase, and Cochrane Library and the reference lists of relevant articles published from inception to October 23, 2017. A Bayesian hierarchical random effects model was used to examine the overall effect size among mixed multiple interventions.
RESULTS: We identified 61 randomised controlled trials of patients with knee and/or hip osteoarthritis. There was no obvious difference in the results between the traditional meta-analysis and the network meta-analysis. The network meta-analysis demonstrated that celecoxib was most likely the best option (SMD, -0.32 [95% CI, -0.38 to -0.25]) for pain, followed by the combination of glucosamine and chondroitin. For physical function, all interventions were significantly superior to oral placebo except for acetaminophen. In terms of stiffness, glucosamine (SMD, -0.36 [95% CI, -0.67 to -0.06]) and celecoxib (SMD, -0.29 [95% CI, -0.51 to -0.08]) were significantly better compared to placebo. In view of safety, compared to placebo only, celecoxib and acetaminophen presented significant differences.
CONCLUSIONS: Given the effectiveness of these non-steroidal anti-inflammatory drugs and symptomatic slow-acting drugs, oral celecoxib is more effective than placebo on relieving pain and improving physical function, followed by the combination of glucosamine and chondroitin. Acetaminophen is likely the least efficacious intervention option. This information, accompanied by the tolerability and economic costs of the included treatments, would be conducive to making decisions for clinicians.
OBJECTIVE: To assess the symptomatic effectiveness and safety of oral symptomatic slow-acting drugs (SYSADOAs) on the treatment of knee and/or hip osteoarthritis, such as chondroitin, glucosamine, and combination treatment with chondroitin plus glucosamine. METHODS: We searched electronic database including PubMed, Embase, Cochrane Library, and the reference lists of relevant articles published from inception to May 22, 2018. An updated meta-analysis was performed to assess the effectiveness of these slow-acting drugs for osteoarthritis. RESULTS: Twenty-six articles describing 30 trials met our inclusion criteria and were included in the meta-analysis. The estimates between chondroitin and placebo showed that chondroitin could alleviate pain symptoms and improve function. Compared with placebo, glucosamine proved significant effect only on stiffness improvement. However, the combination therapy did not have enough evidence to be superior to placebo. Additionally, there was no significant difference in the incidence of AEs and discontinuations of AEs when compared with placebo. CONCLUSIONS: Given the effectiveness of these symptomatic slow-acting drugs, oral chondroitin is more effective than placebo on relieving pain and improving physical function. Glucosamine showed effect on stiffness outcome. Regarding on the limited number of combination therapy, further studies need to investigate the accurate effectiveness. This information accompanied with the tolerability and economic costs of included treatments would be conducive to making decisions for clinicians.
Although glucosamine and chondroitin sulfate have showed beneficial effects on joint tissues in osteoarthritis (OA), their therapeutic use in the clinical setting is still debatable. Hence, a systematic review and meta-analysis of randomized placebo-controlled trials was conducted to investigate the efficacy of glucosamine and chondroitin sulfate on knee OA symptoms. Medline, SCOPUS, Web of Science, and Google Scholar databases were searched for randomized placebo-controlled trials evaluating the effect of orally administered glucosamine and/or chondroitin sulfate on OA symptoms using the Western Ontario and McMaster Universities Osteoarthritis index (WOMAC) and/or the Visual Analog Scale (VAS). Meta-analysis was conducted using a random-effects model and generic inverse-variance method. Heterogeneity was tested using the I2 statistic index. Treatments with glucosamine and chondroitin were found to significantly reduce pain in VAS [weighted mean difference (WMD) - 7.41 mm, 95% CI - 14.31, - 0.51, p = 0.04 and WMD - 8.35 mm, 95% CI - 11.84, - 4.85, p < 0.00001, respectively]. Their combination did not show this behavior (WMD - 0.28 mm, 95% CI - 8.87, 8.32, p = 0.95). None of the glucosamine, chondroitin or their combination had a significant positive effect on the total WOMAC index and its subscores. Oral supplementation with glucosamine or chondroitin sulfate reduces pain in knee OA. However, there is no additional effect using both therapeutic agents in combination for the management of symptomatic knee OA.
Osteoarthritis (OA) is a chronic, highly prevalent and disabling disease that is expected to increase in prevalence secondary to longer life expectancy and a disproportionately aging population. Treatment of OA is only marginally effective and has been focused primarily on symptom control using weight loss, physical therapy, nonsteroidal anti-inflammatory drugs (NSAIDs), acetaminophen, intra-articular steroids or viscosupplementation, topical NSAIDs and analgesics, diacerein (an oral interleukin-1β inhibitor) and finally joint replacement surgery. The use of nutraceuticals in the treatment of OA is common, and scientific studies examining the effects of nutraceuticals on the pathogenesis and treatment of OA are increasing. This review examines the efficacy and safety of select nutraceuticals for the treatment of OA. The reviewed nutraceuticals include glucosamine, chondroitin, collagen hydrolysates (CHs) and avocado-soybean unsaponifiables (ASUs). There have been several clinical trials examining the efficacy of these products and the results demonstrate significant heterogeneity. Significant improvements in pain, function and structural outcomes have been shown for some of the treatment arms or subgroups of patients, but the effects are not consistent across the studies. Glucosamine, chondroitin and the two in combination have been the most extensively studied. Significant improvement in pain and functional indices and a decrease in the loss of joint space width were demonstrated in some but not all studies. CHs showed significant improvement in pain and functional indices for several subgroups of patients, but these findings were not pervasive amongst the treatment arms. ASU has demonstrated positive results with respect to decreased NSAID use in several studies and functional and pain end points in most of the reviewed studies; however, in the two studies examining structural end points, the results were mixed. The safety of these nutraceuticals has been demonstrated across all of the reviewed trials, and there were no significant issues with tolerance. Given the good safety profile of nutraceuticals, the marginal efficacy of conventional treatments, the high prevalence and rate of disability from OA and the possible benefit of nutraceuticals to patients with OA, use of nutraceuticals in select patients is appropriate. An overall recommendation to use nutraceuticals in the treatment of all patients with OA is not strongly supported by the available data. Future studies should focus on standardization of symptomatic and structural outcome measures, be of longer duration and pay careful attention to the content of the investigational product.
Objective: To determine the effect of glucosamine, chondroitin, or the two in combination on joint pain and on radiological progression of disease in osteoarthritis of the hip or knee. Design: Network meta-analysis. Direct comparisons within trials were combined with indirect evidence from other trials by using a Bayesian model that allowed the synthesis of multiple time points. Main outcome measure: Pain intensity. Secondary outcome was change in minimal width of joint space. The minimal clinically important difference between preparations and placebo was prespecified at -0.9 cm on a 10 cm visual analogue scale. Data sources: Electronic databases and conference proceedings from inception to June 2009, expert contact, relevant websites. Eligibility criteria for selecting studies: Large scale randomised controlled trials in more than 200 patients with osteoarthritis of the knee or hip that compared glucosamine, chondroitin, or their combination with placebo or head to head. Results: 10 trials in 3803 patients were included. 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, -0.3 cm (-0.7 to 0.0 cm) for chondroitin, and -0.5 cm (-0.9 to 0.0 cm) for the combination. For none of the estimates did the 95% credible intervals cross the boundary of the minimal clinically important difference. Industry independent trials showed smaller effects than commercially funded trials (P=0.02 for interaction). The differences in changes in minimal width of joint space were all minute, with 95% credible intervals overlapping zero. Conclusions: Compared with placebo, glucosamine, chondroitin, and their combination do not reduce joint pain or have an impact on narrowing of joint space. Health authorities and health insurers should not cover the costs of these preparations, and new prescriptions to patients who have not received treatment should be discouraged.
BACKGROUND: Previous meta-analyses described moderate to large benefits of chondroitin in patients with osteoarthritis. However, recent large-scale trials did not find evidence of an effect.
PURPOSE: To determine the effects of chondroitin on pain in patients with osteoarthritis.
DATA SOURCES: The authors searched the Cochrane Central Register of Controlled Trials (1970 to 2006), MEDLINE (1966 to 2006), EMBASE (1980 to 2006), CINAHL (1970 to 2006), and conference proceedings; checked reference lists; and contacted authors. The last update of searches was performed on 30 November 2006.
STUDY SELECTION: Studies were included if they were randomized or quasi-randomized, controlled trials that compared chondroitin with placebo or with no treatment in patients with osteoarthritis of the knee or hip. There were no language restrictions.
DATA EXTRACTION: The authors extracted data in duplicate. Effect sizes were calculated from the differences in means of pain-related outcomes between treatment and control groups at the end of the trial, divided by the pooled SD. Trials were combined by using random-effects meta-analysis.
DATA SYNTHESIS: 20 trials (3846 patients) contributed to the meta-analysis, which revealed a high degree of heterogeneity among the trials (I2 = 92%). Small trials, trials with unclear concealment of allocation, and trials that were not analyzed according to the intention-to-treat principle showed larger effects in favor of chondroitin than did the remaining trials. When the authors restricted the analysis to the 3 trials with large sample sizes and an intention-to-treat analysis, 40% of patients were included. This resulted in an effect size of -0.03 (95% CI, -0.13 to 0.07; I2 = 0%) and corresponded to a difference of 0.6 mm on a 10-cm visual analogue scale. A meta-analysis of 12 trials showed a pooled relative risk of 0.99 (CI, 0.76 to 1.31) for any adverse event.
LIMITATIONS: For 9 trials, the authors had to use approximations to calculate effect sizes. Trial quality was generally low, heterogeneity among the trials made initial interpretation of results difficult, and exploring sources of heterogeneity in meta-regression and stratified analyses may be unreliable.
CONCLUSIONS: Large-scale, methodologically sound trials indicate that the symptomatic benefit of chondroitin is minimal or nonexistent. Use of chondroitin in routine clinical practice should therefore be discouraged.
BACKGROUND: Pain is the most debilitating symptom in osteoarthritis of the knee (OAK). Aim and methods: To determine the short-term pain-relieving effects of seven commonly used pharmacological agents for OAK pain by performing a systematic review of randomised placebo-controlled trials. RESULTS: In total, 14,060 patients in 63 trials were evaluated. Opioids and oral NSAIDs therapy in patients with moderate to severe pain (mean baseline 64.3 and 72.8 mm on VAS respectively) had maximum efficacies compared to placebo at 2-4 weeks of 10.5 mm [95% CI: 7.4-13.7] and 10.2 mm [95% CI: 8.8-11.2] respectively. The efficacy of opioids may be inflated by high withdrawal rates (24-50%) and 'best-case' scenarios reported in intention-to-treat analyses. In patients with moderate pain scores on VAS (mean range from 51 to 57 mm), intra-articular steroid injections and topical NSAIDs had maximum efficacies at 1-3 weeks of 14.5 mm [95% CI: 9.7-19.2] and 11.6 mm [95% CI: 7.4-15.7], respectively. Paracetamol, glucosamin sulphate and chondroitin sulphate had maximum mean efficacies at 1-4 weeks of only 4.7 mm or lower. Heterogeneity tests revealed that best efficacy values of topical NSAIDs may be slightly deflated, while data for oral NSAIDs may be slightly inflated due to probable patient selection bias. CONCLUSION: Clinical effects from pharmacological interventions in OAK are small and limited to the first 2-3 weeks after start of treatment. The pain-relieving effects over placebo in OAK are smaller than the patient-reported thresholds for relevant improvement. (PsycInfo Database Record (c) 2021 APA, all rights reserved)
This chapter discusses the symptomatic/structural efficacy and the tolerance of the chondroitin sulfate (CS) in the treatment of knee and hip osteoarthritis (OA) through a meta‐analysis of randomized clinical trials. It presents a study in which a search for any randomized, double‐blind, and placebo (PBO)‐controlled prospective trial, whose aim was to assess the symptomatic and/or structural activity of oral CS in the treatment of knee or hip OA, was performed through data sources and then through a manual search of the reference section of all articles retrieved by the primary search. This search was limited to articles published in extenso in peer‐reviewed journals between 1980 and 2005, in English or French languages, presenting sufficient data and lasting more than 4 weeks. A modest effect of the CS on the relief of pain and on the improvement of the joint function has been found. Osteoarthritis is the most common form of arthritis, affecting the knee in 30% and the hip in 4–10% of people aged 65 and over. Even if roughly 50% of them only have signs and symptoms, the number of adults clinically affected by this disease is considerable especially in the elderly and is increasing with the increasing average age in the populations.
To compare the efficacies of oral glucosamine, chondroitin, the combination of glucosamine and chondroitin, acetaminophen and celecoxib on the treatment of knee and/or hip osteoarthritis.
METHODS:
We searched electronic databases including PubMed, Embase, and Cochrane Library and the reference lists of relevant articles published from inception to October 23, 2017. A Bayesian hierarchical random effects model was used to examine the overall effect size among mixed multiple interventions.
RESULTS:
We identified 61 randomised controlled trials of patients with knee and/or hip osteoarthritis. There was no obvious difference in the results between the traditional meta-analysis and the network meta-analysis. The network meta-analysis demonstrated that celecoxib was most likely the best option (SMD, -0.32 [95% CI, -0.38 to -0.25]) for pain, followed by the combination of glucosamine and chondroitin. For physical function, all interventions were significantly superior to oral placebo except for acetaminophen. In terms of stiffness, glucosamine (SMD, -0.36 [95% CI, -0.67 to -0.06]) and celecoxib (SMD, -0.29 [95% CI, -0.51 to -0.08]) were significantly better compared to placebo. In view of safety, compared to placebo only, celecoxib and acetaminophen presented significant differences.
CONCLUSIONS:
Given the effectiveness of these non-steroidal anti-inflammatory drugs and symptomatic slow-acting drugs, oral celecoxib is more effective than placebo on relieving pain and improving physical function, followed by the combination of glucosamine and chondroitin. Acetaminophen is likely the least efficacious intervention option. This information, accompanied by the tolerability and economic costs of the included treatments, would be conducive to making decisions for clinicians.
