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Systematic review

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Effectiveness and safety of non-steroidal anti-inflammatory drugs and opioid treatment for knee and hip osteoarthritis: network meta-analysis.

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Journal BMJ (Clinical research ed.)
Year 2021
Links Pubmed DOI PubMed Central

This article includes 175 Primary studies 183 Primary studies (175 references)

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OBJECTIVE: To assess the effectiveness and safety of different preparations and doses of non-steroidal anti-inflammatory drugs (NSAIDs), opioids, and paracetamol for knee and hip osteoarthritis pain and physical function to enable effective and safe use of these drugs at their lowest possible dose. DESIGN: Systematic review and network meta-analysis of randomised trials. DATA SOURCES: Cochrane Central Register of Controlled Trials (CENTRAL), Medline, Embase, regulatory agency websites, and ClinicalTrials.gov from inception to 28 June 2021. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Randomised trials published in English with ≥100 patients per group that evaluated NSAIDs, opioids, or paracetamol (acetaminophen) to treat osteoarthritis. OUTCOMES AND MEASURES: The prespecified primary outcome was pain. Physical function and safety outcomes were also assessed. REVIEW METHODS: Two reviewers independently extracted outcomes data and evaluated the risk of bias of included trials. Bayesian random effects models were used for network meta-analysis of all analyses. Effect estimates are comparisons between active treatments and oral placebo. RESULTS: 192 trials comprising 102 829 participants examined 90 different active preparations or doses (68 for NSAIDs, 19 for opioids, and three for paracetamol). Five oral preparations (diclofenac 150 mg/day, etoricoxib 60 and 90 mg/day, and rofecoxib 25 and 50 mg/day) had ≥99% probability of more pronounced treatment effects than the minimal clinically relevant reduction in pain. Topical diclofenac (70-81 and 140-160 mg/day) had ≥92.3% probability, and all opioids had ≤53% probability of more pronounced treatment effects than the minimal clinically relevant reduction in pain. 18.5%, 0%, and 83.3% of the oral NSAIDs, topical NSAIDs, and opioids, respectively, had an increased risk of dropouts due to adverse events. 29.8%, 0%, and 89.5% of oral NSAIDs, topical NSAIDs, and opioids, respectively, had an increased risk of any adverse event. Oxymorphone 80 mg/day had the highest risk of dropouts due to adverse events (51%) and any adverse event (88%). CONCLUSIONS: Etoricoxib 60 mg/day and diclofenac 150 mg/day seem to be the most effective oral NSAIDs for pain and function in patients with osteoarthritis. However, these treatments are probably not appropriate for patients with comorbidities or for long term use because of the slight increase in the risk of adverse events. Additionally, an increased risk of dropping out due to adverse events was found for diclofenac 150 mg/day. Topical diclofenac 70-81 mg/day seems to be effective and generally safer because of reduced systemic exposure and lower dose, and should be considered as first line pharmacological treatment for knee osteoarthritis. The clinical benefit of opioid treatment, regardless of preparation or dose, does not outweigh the harm it might cause in patients with osteoarthritis. SYSTEMATIC REVIEW REGISTRATION: PROSPERO number CRD42020213656.

Systematic review

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Effects of Oral Glucosamine Sulfate on Osteoarthritis-Related Pain and Joint-Space Changes: Systematic Review and Meta-Analysis.

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Journal Journal of special operations medicine : a peer reviewed journal for SOF medical professionals
Year 2018
Links Pubmed DOI

This article includes 17 Primary studies 17 Primary studies (17 references)

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BACKGROUND: Osteoarthritis (OA) is a disorder involving deterioration of articular cartilage and underlying bone and is associated with symptoms of pain and disability. Glucosamine is a component of articular cartilage naturally synthesized in the body from glucose and incorporated into substances contained in the cartilage. It has been suggested that consumption of glucosamine may reduce the pain of OA and may have favorable effects on structural changes in the cartilage. This article presents a systematic review and meta-analysis of the effectiveness of orally consumed glucosamine sulfate (GS) on OA-related pain and joint structural changes. METHODS: PubMed and Ovid Embase were searched using specific search terms to find randomized, double-blinded, placebo-controlled trials on the effects of GS on pain and/or joint-space narrowing. The outcome measure was the standardized mean difference (SMD), which was the improvement in the placebo groups minus the improvement in the GS groups divided by the pooled standard deviation. RESULTS: There were 17 studies meeting the review criteria for pain, and the summary SMD was -0.35, with a 95% confidence interval (95% CI) = -0.54 to -0.16 (negative SMD is in favor of GS). Of the 17 studies, 7 showed a statistically significant reduction in pain from GS use. Four studies met the review criteria for joint space narrowing with a summary SMD = -0.10 (95% CI = -0.23 to +0.04). Studies without involvement of the commercial glucosamine industry had a lower (but still significant) pain reduction efficacy (summary SMD = -0.19, 95% CI = -0.39 to -0.02) than those with industry involvement. Several smaller dosages throughout the day had larger pain reduction effects than a single daily large dose (1500 mg). CONCLUSION: These data indicate that GS may have a small to moderate effect in reducing OA-related pain but little effect on joint-space narrowing. Until there is more definitive evidence, healthcare providers should be cautious in recommending use of GS to their patients. Because GS dosages used in studies to date resulted in mild and transient adverse effects, and these were similar to that experienced by patients receiving placebos, larger GS doses possibly could be investigated in future studies.

Systematic review

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Comparative effectiveness of glucosamine, chondroitin, acetaminophen or celecoxib for the treatment of knee and/or hip osteoarthritis: a network meta-analysis.

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Authors Zhu X , Wu D , Sang L , Wang Y , Shen Y , Zhuang X , Chu M , Jiang L
Journal Clinical and experimental rheumatology
Year 2018
Links Pubmed

This article includes 58 Primary studies 59 Primary studies (58 references)

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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.

Systematic review

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Effectiveness and safety of glucosamine and chondroitin for the treatment of osteoarthritis: a meta-analysis of randomized controlled trials.

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Authors Zhu X , Sang L , Wu D , Rong J , Jiang L
Journal Journal of orthopaedic surgery and research
Year 2018
Links Pubmed DOI PubMed Central

This article includes 26 Primary studies 25 Primary studies (26 references)

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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.

Systematic review

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Efficacy and safety of glucosamine, diacerein, and NSAIDs in osteoarthritis knee: a systematic review and network meta-analysis.

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Journal European journal of medical research
Year 2015
Links Pubmed DOI PubMed Central

This article is included in 1 Broad synthesis 30 Broad syntheses (1 reference)

This article includes 31 Primary studies 30 Primary studies (31 references)

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BACKGROUND: To conduct a systematic review and network meta-analysis of randomized controlled trials (RCTs) with the aims of comparing relevant clinical outcomes (that is, visual analog scores (VAS), total and sub-Western Ontario and McMaster Universities Osteoarthritis index (WOMAC) scores, Lequesne algofunctional index, joint space width change, and adverse events) between diacerein, glucosamine, and placebo. METHODS: Medline and Scopus databases were searched from inception to 29 August 2014, using PubMed and Scopus search engines and included RCTs or quasi-experimental designs comparing clinical outcomes between treatments. Data were extracted from original studies. A network meta-analysis was performed by applying weight regression for continuous outcomes and a mixed-effect Poisson regression for dichotomous outcomes. RESULTS: Thirty-one of 505 identified studies were eligible. Compared to placebo, glucosamine showed a significant improvement with unstandardized mean differences (UMD) in total WOMAC, pain WOMAC, function WOMAC, and Lequesne score of -2.49 (95% confidence interval (CI) -4.14, -0.83), -0.75 (95% CI: -1.18, -0.32), -4.78 (95% CI: -5.96, -3.59), and -1.03 (95% CI: -1.34, -0.72), respectively. Diacerein clinically improves visual analog scores, function WOMAC, and stiffness WOMAC with UMD values of -2.23 (95% CI: -2.82, -1.64), -6.64 (95% CI: -10.50, -2.78), and -0.68 (95% CI: -1.20, -0.16) when compared to placebo. CONCLUSIONS: The network meta-analysis suggests that diacerein and glucosamine are equally efficacious for symptom relief in knee OA, but that the former has more side effects.

Systematic review

Unclassified

Chondroprotection and the Prevention of Osteoarthritis Progression of the Knee: A Systematic Review of Treatment Agents.

Journal The American journal of sports medicine
Year 2015
Links Pubmed DOI

This article is included in 2 Broad syntheses 13 Broad syntheses (2 references)

This article includes 13 Primary studies 13 Primary studies (13 references)

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BACKGROUND: Structure-modifying medications or nutraceuticals may be an effective treatment for osteoarthritis. This study identified 12 treatments that may possess chondroprotective properties: oral glucosamine; chondroitin; nonsteroidal anti-inflammatory drugs (NSAIDs); polyunsaturated fatty acids; S-adenosylmethionine; avocado and soybean unsaponifiable fractions; methylsulfonylmethane; vitamins C, D, and E; intra-articular injections of hyaluronic acid; and platelet-rich plasma (PRP). PURPOSE: To perform a systematic review of randomized controlled trials for the effectiveness of each agent in preserving articular cartilage of the knee and delaying the progression of osteoarthritis. STUDY DESIGN: Systematic review; Level of evidence, 2. METHODS: A literature search was performed using PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials. Searches were performed using "treatment," "osteoarthritis," and "knee" as keywords. Selection criteria included randomized controlled trials of ≥12 months, with a placebo control, measuring radiographic changes in joint space width, cartilage volume, or radiographic progression of osteoarthritis. The primary outcome was changes in joint integrity measures. RESULTS: A total of 3514 studies were identified from the initial search, 13 of which met inclusion criteria. Treatment with chondroitin sulfate showed a significant reduction in cartilage loss in 3 of 4 studies identified compared with placebo. Two of 3 trials identified for glucosamine also reported significant structural effects relative to placebo. Intra-articular hyaluronic acid was effective in lowering the rate of cartilage loss in only 1 of 3 studies identified versus placebo. Of the 6 studies identified for NSAIDs, vitamin E, and vitamin D, none showed any structural effect compared with placebo. No studies were found that met the inclusion criteria for polyunsaturated fatty acids, S-adenosylmethionine, avocado and soybean unsaponifiable fractions, methylsulfonylmethane, vitamin C, or PRP. CONCLUSION: For patients with or at risk for osteoarthritis, the use of glucosamine and chondroitin sulfate may serve as a nonoperative means to protect joint cartilage and delay osteoarthritis progression. Hyaluronic acid injections showed variable efficacy, while NSAIDs and vitamins E and D showed no effect on osteoarthritis progression. The other agents evaluated had no evidence in the literature to support or refute their use for chondroprotection.

Systematic review

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Risk of bias and brand explain the observed inconsistency in trials on glucosamine for symptomatic relief of osteoarthritis: a meta-analysis of placebo-controlled trials.

Journal Arthritis care & research
Year 2014
Links Pubmed DOI

This article includes 25 Primary studies 25 Primary studies (25 references)

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OBJECTIVE: To determine whether study sponsor, chemical formulation, brand of glucosamine, and/or risk of bias explain observed inconsistencies in trials of glucosamine's efficacy for treating pain in osteoarthritis (OA). METHODS: A systematic review and stratified meta-analysis of randomized placebo-controlled trials was performed, and random-effects models were applied with inconsistency (I(2) ) and heterogeneity (tau(2) ) estimated using Review Manager and SAS, respectively. The major outcome was reduction of pain; the standardized mean difference (SMD [95% confidence interval (95% CI)]) served as effect size. RESULTS: The inclusion criteria yielded 25 trials (3,458 patients). Glucosamine moderately reduced pain (SMD -0.51 [95% CI -0.72, -0.30]), although a high level of between-trial inconsistency was observed (I(2) = 88%). The single most important explanation (i.e., covariate) was brand, reducing heterogeneity by 41% (P = 0.00032). Twelve trials (1,437 patients) using the Rottapharm/Madaus product resulted in significant pain reduction (SMD -1.07 [95% CI -1.47, -0.67]), although a sensitivity analysis of 3 low risk of bias trials using the Rottapharm/Madaus product showed less promising results (SMD -0.27 [95% CI -0.43, -0.12]), which is only a small effect size. Thirteen trials (1,963 patients) using non-Rottapharm/Madaus products consistently failed to show a reduction in pain (SMD -0.11 [95% CI -0.46, 0.24]). The second most important explanation was overall risk of bias (reducing heterogeneity by 32%). CONCLUSION: Most of the observed heterogeneity in glucosamine trials is explained by brand. Trials using the Rottapharm/Madaus glucosamine product had a superior outcome on pain in OA compared to other preparations of glucosamine. Large inconsistency was found, however. Low risk of bias trials, using the Rottapharm/Madaus product, revealed a small effect size.

Systematic review

Unclassified

Efficacies of different preparations of glucosamine for the treatment of osteoarthritis: a meta-analysis of randomised, double-blind, placebo-controlled trials.

Authors Wu D , Huang Y , Gu Y , Fan W
Journal International journal of clinical practice
Year 2013
Links Pubmed DOI

This article is included in 1 Structured summary of systematic reviews 18 Structured summaries of systematic reviews (1 reference) 1 Broad synthesis 18 Broad syntheses (1 reference)

This article includes 19 Primary studies 18 Primary studies (19 references)

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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(2) 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(2) 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(2) remained high (I(2) = 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(2) = 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.

Systematic review

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Nutraceuticals in the management of osteoarthritis : a critical review.

Authors Ragle RL , Sawitzke AD
Journal Drugs & aging
Year 2012
Links Pubmed DOI

This article includes 25 Primary studies 22 Primary studies (25 references)

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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.

Systematic review

Unclassified

Efficacy of glucosamine, chondroitin, and methylsulfonylmethane for spinal degenerative joint disease and degenerative disc disease: a systematic review.

Authors Stuber K , Sajko S , Kristmanson K
Journal The Journal of the Canadian Chiropractic Association
Year 2011
Links Pubmed DOI PubMed Central

This article is included in 1 Structured summary of systematic reviews 27 Structured summaries of systematic reviews (1 reference) 4 Broad syntheses 27 Broad syntheses (4 references)

This article includes 27 Primary studies 27 Primary studies (27 references)

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BACKGROUND: Nutritional supplements are commonly used for a variety of musculoskeletal conditions, including knee and hip degenerative joint disease. Although these supplements are occasionally recommended for patients with degenerative disc disease and spinal degenerative joint disease, the evidence supporting this use is unknown. OBJECTIVE: To systematically search and assess the quality of the literature on the use of glucosamine, chondroitin sulfate, and methylsulfonylmethane for the treatment of spinal osteoarthritis / degenerative joint disease, and degenerative disc disease. DATA SOURCES: The Index of Chiropractic Literature, AMED, Medline, and CINAHL were searched for randomized controlled trials in English from 1984 to July 2009. DATA EXTRACTION AND SYNTHESIS: Data from studies meeting the inclusion criteria was extracted and reviewed by three reviewers. The Jadad scale was used to assess study quality. No attempts were made at meta-analysis due to variation in study design. RESULTS: Two articles met the inclusion criteria. One study was found to have good quality but reported negative results for the supplemented group compared with placebo, the other study had low quality but reported significant positive results for the supplemented group when compared with a no intervention control group. CONCLUSION: There was little literature found to support the use of common nutritional supplements for spinal degeneration, making it difficult to determine whether clinicians should recommend them.