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Interventions for osteoarthritis pain: A systematic review with network meta-analysis of existing Cochrane reviews

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Journal Osteoarthritis and cartilage open
Year 2022
Links Pubmed DOI PubMed Central

This article includes 22 Systematic reviews Systematic reviews (22 references)

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OBJECTIVE: To conduct a network meta-analysis comparing all treatments for osteoarthritis (OA) pain in the Cochrane Library. DESIGN: The Cochrane Library and Epistemonikos were searched for randomized controlled trials (RCTs) about treatments for hip and knee OA. We constructed 17 broad categories, comprising drug treatments, exercise, surgery, herbs, orthotics, passive treatments, regenerative medicine, diet/weight loss, combined treatments, and controls. In addition to a full network analysis, we compared the direct/indirect effects, and studies with shorter-/longer follow-up. CINeMA software was used for assessing confidence in network meta-analysis estimates. RESULTS: We included 35 systematic reviews including 445 RCTs. There were 153 treatments for OA. In total, 491 comparisons were related to knee OA, less on hip OA, and only nine on hand OA. Six treatment categories showed clinically significant effects favoring treatment over control on pain. "Diet/weight loss" and "Surgery" had effect sizes close to zero. The network as a whole was not coherent. Of 136 treatment comparisons, none were rated as high confidence, six as moderate, 13 as low, and 117 as very low. CONCLUSIONS: Direct comparison of different available treatment options for OA is desirable, however not currently feasible in practice, due to heterogeneous study populations and lack of clear descriptions of control interventions. We found that many treatments were effective, but since the network as a whole was not coherent and lacked high confidence in the treatment comparisons, we could not produce a ranking of effects.

Broad synthesis / Living FRISBEE

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Is glucosamine effective for osteoarthritis?

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Journal Medwave
Year 2017
Links Pubmed DOI

This article includes 11 Systematic reviews Systematic reviews (11 references) 36 Primary studies Primary studies (36 references)

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Osteoarthritis is the most prevalent chronic articular disease, in which pain is one of the main symptoms and a major determinant of functional loss. Several therapeutic options have been proposed, including glucosamine, but its actual usefulness has not yet been established. To answer this question, we searched in Epistemonikos database, which is maintained by screening multiple databases. We identified 11 systematic reviews including 35 randomized trials answering the question of interest. We extracted data, conducted a meta-analysis and generated a summary of findings table using the GRADE approach. We concluded it is not clear whether glucosamine decreases pain or improves functionality in osteoarthritis because the certainty of the evidence is very low.

Broad synthesis / Living FRISBEE

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Is chondroitin sulfate effective for osteoarthritis?

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Journal Medwave
Year 2017
Links Pubmed DOI

This article includes 13 Systematic reviews Systematic reviews (13 references) 52 Primary studies Primary studies (52 references)

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Osteoarthritis is the most prevalent chronic articular disease, in which pain is one of the main symptoms and the major determinant of functional loss. Several therapeutic options have been proposed, including chondroitin sulfate, but its actual usefulness has not yet been established. To answer this question we searched in Epistemonikos database, which is maintained by screening multiple information sources. We identified 13 systematic reviews including 50 randomized trials overall. We extracted data, conducted a meta-analysis and generated a summary of findings table using the GRADE approach. We concluded it is not clear whether the use of chondroitin sulfate leads to an improvement in pain or functionality in osteoarthritis because the certainty of the evidence is very low.

Broad synthesis / Living FRISBEE

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Are intraarticular steroids effective for knee osteoarthritis?

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Journal Medwave
Year 2016
Links Pubmed DOI

This article includes 12 Systematic reviews Systematic reviews (12 references) 39 Primary studies Primary studies (39 references)

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Knee osteoarthritis is a chronic disabling condition that is both progressive and irreversible. Intraarticular steroids are commonly used to reduce osteoarthritis symptoms and to minimize the need for surgery. Nevertheless, debate still exists regarding the efficacy and safety of steroids. To address this point, we searched Epistemonikos database which is maintained by screening 30 separate databases and identified 12 systematic reviews including 41 studies addressing steroids use in knee osteoarthritis. Of these, 40 were randomized trials. The evidence from these studies was combined using meta-analysis, and a summary of findings table was constructed following the GRADE approach. We concluded intraarticular steroid use slightly decreases short-term pain, makes little or no difference in the mid-term, and may have no effects in the long-term.

Broad synthesis / Guideline

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OARSI guidelines for the non-surgical management of knee osteoarthritis.

Journal Osteoarthritis and cartilage / OARS, Osteoarthritis Research Society
Year 2014
Links Pubmed DOI

This article includes 17 Systematic reviews Systematic reviews (17 references) 11 Primary studies Primary studies (11 references)

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OBJECTIVE: To develop concise, up-to-date, patient-focused, evidence-based, expert consensus guidelines for the management of knee osteoarthritis (OA), intended to inform patients, physicians, and allied healthcare professionals worldwide. METHOD: Thirteen experts from relevant medical disciplines (primary care, rheumatology, orthopedics, physical therapy, physical medicine and rehabilitation, and evidence-based medicine), three continents and ten countries (USA, UK, France, Netherlands, Belgium, Sweden, Denmark, Australia, Japan, and Canada) and a patient representative comprised the Osteoarthritis Guidelines Development Group (OAGDG). Based on previous OA guidelines and a systematic review of the OA literature, 29 treatment modalities were considered for recommendation. Evidence published subsequent to the 2010 OARSI guidelines was based on a systematic review conducted by the OA Research Society International (OARSI) evidence team at Tufts Medical Center, Boston, USA. Medline, EMBASE, Google Scholar, Web of Science, and the Cochrane Central Register of Controlled Trials were initially searched in first quarter 2012 and last searched in March 2013. Included evidence was assessed for quality using Assessment of Multiple Systematic Reviews (AMSTAR) criteria, and published criticism of included evidence was also considered. To provide recommendations for individuals with a range of health profiles and OA burden, treatment recommendations were stratified into four clinical sub-phenotypes. Consensus recommendations were produced using the RAND/UCLA Appropriateness Method and Delphi voting process. Treatments were recommended as Appropriate, Uncertain, or Not Appropriate, for each of four clinical sub-phenotypes and accompanied by 1-10 risk and benefit scores. RESULTS: Appropriate treatment modalities for all individuals with knee OA included biomechanical interventions, intra-articular corticosteroids, exercise (land-based and water-based), self-management and education, strength training, and weight management. Treatments appropriate for specific clinical sub-phenotypes included acetaminophen (paracetamol), balneotherapy, capsaicin, cane (walking stick), duloxetine, oral non-steroidal anti-inflammatory drugs (NSAIDs; COX-2 selective and non-selective), and topical NSAIDs. Treatments of uncertain appropriateness for specific clinical sub-phenotypes included acupuncture, avocado soybean unsaponfiables, chondroitin, crutches, diacerein, glucosamine, intra-articular hyaluronic acid, opioids (oral and transdermal), rosehip, transcutaneous electrical nerve stimulation, and ultrasound. Treatments voted not appropriate included risedronate and electrotherapy (neuromuscular electrical stimulation). CONCLUSION: These evidence-based consensus recommendations provide guidance to patients and practitioners on treatments applicable to all individuals with knee OA, as well as therapies that can be considered according to individualized patient needs and preferences.

Broad synthesis

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Analgesics for Osteoarthritis: An Update of the 2006 Comparative Effectiveness Review

Book AHRQ Comparative Effectiveness Reviews
Year 2011
Links Pubmed

This article includes 73 Primary studies Primary studies (73 references) 24 Systematic reviews Systematic reviews (24 references)

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OBJECTIVES: To update a previous report on the comparative benefits and harms of oral non-steroidal anti-inflammatory drugs (NSAIDs), acetaminophen, over-the-counter supplements (chondroitin and glucosamine), and topical agents (NSAIDs and rubefacients, including capsaicin) for osteoarthritis. DATA SOURCES: Ovid MEDLINE (1996–January 2011), the Cochrane Database (through fourth quarter 2010), and reference lists. REVIEW METHODS: We included randomized trials, cohort studies, case-control studies, and systematic reviews that met predefined inclusion criteria. For each study, investigators abstracted details about the study population, study design, data analysis, followup, and results, and they assessed quality using predefined criteria. We assessed the overall strength of each body of evidence using predefined criteria, which included the type and number of studies; risk of bias; consistency; and precision of estimates. Meta-analyses were not performed, though pooled estimates from previously published studies were reported. RESULTS: A total of 273 studies were included. Overall, we found no clear differences in efficacy for pain relief associated with different NSAIDs. Celecoxib was associated with a lower risk of ulcer complications (RR 0.23, 95% CI 0.07 to 0.76) compared to nonselective NSAIDs. Coprescribing of proton pump inhibitors, misoprostol, and H2-antagonists reduce the risk of endoscopically detected gastroduodenal ulcers compared to placebo in persons prescribed NSAIDs. Celecoxib and most nonselective, nonaspirin NSAIDs appeared to be associated with an increased risk of serious cardiovascular (CV) harms. There was no clear association between longer duration of NSAID use or higher doses and increased risk of serious CV harms. There were no clear differences between glucosamine or chondroitin and oral NSAIDs for pain or function, though evidence from a systematic review of higher-quality trials suggests that glucosamine had some very small benefits over placebo for pain. Head-to-head trials showed no difference between topical and oral NSAIDs for efficacy in patients with localized osteoarthritis, lower risk of gastrointestinal (GI) adverse events, and higher risk of dermatological adverse events, but serious GI and CV harms were not evaluated. No head-to-head trials compared topical salicylates or capsaicin to oral NSAIDs. CONCLUSIONS: Each of the analgesics evaluated in this report was associated with a unique set of risks and benefits. Choosing the optimal analgesic for an individual with osteoarthritis requires careful consideration and thorough discussion of the relevant tradeoffs.

Broad synthesis

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The clinical effectiveness of glucosamine and chondroitin supplements in slowing or arresting progression of osteoarthritis of the knee: A systematic review and economic evaluation

Journal Health technology assessment (Winchester, England)
Year 2009
Links Pubmed Health Technology Assessment (HTA) DOI crd.york.ac.uk

This article includes 5 Systematic reviews Systematic reviews (5 references)

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Objective: To assess the clinical effectiveness and cost-effectiveness of glucosamine sulphate/hydrochloride and chondroitin sulphate in modifying the progression of osteoarthritis (OA) of the knee. Data sources: Electronic databases were searched from 1950 to 2008 and included: MEDLINE and PubMed; EMBASE; Cochrane Library (including Cochrane Systematic Reviews Database, CENTRAL, DARE, NHS EED and HTA databases); Allied and Complementary Medicine (AMED); National Research Register (NRR); Web of Science Proceedings; Current Controlled Trials; and Clinical Trials.gov. Other sources included bibliographies of retrieved papers, registered but unpublished trials, internet searches and the Food Standards Agency website. Review methods: A search was conducted for systematic reviews of randomised controlled trials (RCTs), which were used to identify RCTs of at least 12 months' duration and updated with searches for primary studies. A cost-effectiveness model was constructed using cohort simulation and drawing on available evidence. Sensitivity analysis was undertaken and value of information analysis conducted. A review of studies of mechanism of action was carried out to explore the biological plausibility of the preparations. Results: Five systematic reviews and one clinical guideline met the inclusion criteria. They reported inconsistent conclusions with only modest effects on reported pain and function. A reduction in joint space narrowing was more consistently observed, but the effect size was small and the clinical significance uncertain. A separate review of eight primary trials of > 12 months' duration showed evidence of statistically significant improvements in joint space loss, pain and function for glucosamine sulphate, but the clinical importance of these differences was not clear. In two studies of glucosamine sulphate, the need for knee arthroplasty was reduced from 14.5% to 6.3% at 8 years' follow-up. For other preparations of glucosamine, chondroitin and combination therapy, there was less evidence to support a clinical effect. Cost-effectiveness modelling was restricted to glucosamine sulphate. Over a lifetime horizon the incremental cost per quality-adjusted life-year (QALY) gain for adding glucosamine sulphate to current care was estimated to be £21,335. Deterministic sensitivity analysis suggested that the cost-effectiveness of glucosamine sulphate therapy was particularly dependent on the magnitude of the quality of life (QoL) gain, the change in knee arthroplasty probability with therapy and the discount rate. At a cost per QALY gained threshold of £20,000, the likelihood that glucosamine sulphate is more cost-effective than current care is 0.43, while at a threshold of £30,000, the probability rises to 0.73. Probabilistic sensitivity analysis showed that estimates were imprecise and subject to a degree of decision uncertainty. Value of information analysis demonstrated the need for further research. Several biologically plausible mechanisms of action for glucosamine sulphate and chondroitin were proposed. Conclusions: There was evidence that glucosamine sulphate shows some clinical effectiveness in the treatment of OA of the knee. No trial data came from the UK and caution should be exercised in generalising the findings to the UK health-care setting. Cost-effectiveness was not conclusively demonstrated. There was evidence to support the potential clinical impact of glucosamine sulphate. The value of information analysis identified three research priorities: QoL, structural outcomes and knee arthroplasty. The biological mechanism of glucosamine sulphate and chondroitin remains uncertain and, in particular, the proposal that the active substance may be sulphate should be explored further. © 2009 Queen's Printer and Controller of HMSO. All rights reserved.

Broad synthesis

Unclassified

Osteoarthritis of the knee.

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Authors Scott D , Kowalczyk A
Journal BMJ clinical evidence
Year 2007
Links Pubmed PubMed Central

This article includes 75 Primary studies Primary studies (75 references) 11 Systematic reviews Systematic reviews (11 references)

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INTRODUCTION: Osteoarthritis of the knee affects about 10% of adults aged over 60 years, with risk increased in those with obesity, and joint damage or abnormalities. Progression of disease on x rays is commonplace, but x ray changes don't correlate well with clinical symptoms. METHODS AND OUTCOMES: We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of non-surgical treatments for osteoarthritis of the knee? What are the effects of surgical treatments for osteoarthritis of the knee? We searched: Medline, Embase, The Cochrane Library and other important databases up to October 2006 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). RESULTS: We found 74 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. CONCLUSIONS: In this systematic review we present information relating to the effectiveness and safety of the following interventions: acupuncture, capsaicin, chondroitin, education to aid self-management, exercise and physiotherapy, glucosamine, insoles, intra-articular corticosteroids, intra-articular hyaluronan, joint bracing, knee replacement, non-steroidal anti-inflammatory drugs (including topical non-steroidal anti-inflammatory drugs), opioid analgesics, osteotomy, simple analgesics, and taping.

Broad synthesis / Overview of systematic reviews

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Treatment of primary and secondary osteoarthritis of the knee.

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Journal Evidence report/technology assessment
Year 2007
Links Pubmed PubMed Central

This article includes 86 Primary studies Primary studies (86 references) 11 Systematic reviews Systematic reviews (11 references)

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OBJECTIVES: Systematic review of outcomes of three treatments for osteoarthritis (OA) of the knee: intra-articular viscosupplementation; oral glucosamine, chondroitin or the combination; and arthroscopic lavage or debridement. DATA SOURCES: We abstracted data from: 42 randomized, controlled trials (RCTs) of viscosupplementation, all but one synthesized among six meta-analyses; 21 RCTs of glucosamine/chondroitin, 16 synthesized among 6 meta-analyses; and 23 articles on arthroscopy. The search included foreign-language studies and relevant conference proceedings. REVIEW METHODS: The review methods were defined prospectively in a written protocol. We sought systematic reviews, meta-analyses, and RCTs published in full or in abstract. Where randomized trials were few, we sought other study designs. We independently assessed the quality of all primary studies. RESULTS: Viscosupplementation trials generally report positive effects on pain and function scores compared to placebo, but the evidence on clinical benefit is uncertain, due to variable trial quality, potential publication bias, and unclear clinical significance of the changes reported. The Glucosamine/Chondroitin Arthritis Intervention Trial (GAIT), a large (n=1,583), high-quality, National Institutes of Health-funded, multicenter RCT showed no significant difference compared to placebo. Glucosamine sulfate has been reported to be more effective than glucosamine hydrochloride, which was used in GAIT, but the evidence is not sufficient to draw conclusions. Clinical studies of glucosamine effect on glucose metabolism are short term, or if longer (e.g., 3 years), excluded patients with metabolic disorders. The best available evidence for arthroscopy, a single sham-controlled RCT (n=180), showed that arthroscopic lavage with or without debridement was equivalent to placebo. The main limitations of this trial are the use of a single surgeon and enrollment of patients at a single Veterans Affairs Medical Center. No studies reported separately on patients with secondary OA of the knee. The only comparative study was an underpowered, poor-quality trial comparing viscosupplementation to arthroscopy with debridement. CONCLUSIONS: Osteoarthritis of the knee is a common condition. The three interventions reviewed in this report are widely used in the treatment of OA of the knee, yet the best available evidence does not clearly demonstrate clinical benefit. Uncertainty regarding clinical benefit can be resolved only by rigorous, multicenter RCTs. In addition, given the public health impact of OA of the knee, research on new approaches to prevention and treatment should be given high priority.