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      Intra-articular Hyaluronic Acid in Treating Knee Osteoarthritis: a PRISMA-Compliant Systematic Review of Overlapping Meta-analysis

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          Abstract

          Numerous meta-analyses have been conducted aiming to compare hyaluronic acid (HA) and placebo in treating knee osteoarthritis (OA). Nevertheless, the conclusions of these meta-analyses are not in consistency. The purpose of the present study was to perform a systematic review of overlapping meta-analyses investigating the efficacy and safety of HA for Knee OA and to provide treatment recommendations through the best evidence. A systematic review was conducted based on the PRISMA guidelines. The meta-analyses and/or systematic reviews that compared HA and placebo for knee OA were identified. AMSTAR instrument was used to evaluate the methodological quality of individual study. The information of heterogeneity within each variable was fetched for the individual studies. Which meta-analyses can provide best evidence was determined according to Jadad algorithm. Twelve meta-analyses met the eligibility requirements. The Jadad decision making tool suggests that the highest quality review should be selected. As a result, a high-quality Cochrane review was included. The present systematic review of overlapping meta-analyses demonstrates that HA is an effective intervention in treating knee OA without increased risk of adverse events. Therefore, the present conclusions may help decision makers interpret and choose among discordant meta-analyses.

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          Pathogenesis and management of pain in osteoarthritis.

          The term osteoarthritis describes a common, age-related, heterogeneous group of disorders characterised pathologically by focal areas of loss of articular cartilage in synovial joints, associated with varying degrees of osteophyte formation, subchondral bone change, and synovitis. Joint damage is caused by a mixture of systemic factors that predispose to the disease, and local mechanical factors that dictate its distribution and severity. Various genetic abnormalities have been described, but most sporadic osteoarthritis probably depends on minor contributions from several genetic loci. Osteoarthritic joint damage may be associated with clinical problems, but the severity of joint disease is only weakly related to that of the clinical problem. For this reason the associations and pathogenesis of pain are in as much need of investigation as joint damage. Subchondral bone and synovium may be responsible for nociceptive stimuli, and peripheral neuronal sensitisation is an important feature, and can result in normal activities (such as walking) causing pain. Central pain sensitisation can also occur, and psychosocial factors are important determinants of pain severity. We present a stepwise approach to the management of osteoarthritis.
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            External Validation of a Measurement Tool to Assess Systematic Reviews (AMSTAR)

            Background Thousands of systematic reviews have been conducted in all areas of health care. However, the methodological quality of these reviews is variable and should routinely be appraised. AMSTAR is a measurement tool to assess systematic reviews. Methodology AMSTAR was used to appraise 42 reviews focusing on therapies to treat gastro-esophageal reflux disease, peptic ulcer disease, and other acid-related diseases. Two assessors applied the AMSTAR to each review. Two other assessors, plus a clinician and/or methodologist applied a global assessment to each review independently. Conclusions The sample of 42 reviews covered a wide range of methodological quality. The overall scores on AMSTAR ranged from 0 to 10 (out of a maximum of 11) with a mean of 4.6 (95% CI: 3.7 to 5.6) and median 4.0 (range 2.0 to 6.0). The inter-observer agreement of the individual items ranged from moderate to almost perfect agreement. Nine items scored a kappa of >0.75 (95% CI: 0.55 to 0.96). The reliability of the total AMSTAR score was excellent: kappa 0.84 (95% CI: 0.67 to 1.00) and Pearson's R 0.96 (95% CI: 0.92 to 0.98). The overall scores for the global assessment ranged from 2 to 7 (out of a maximum score of 7) with a mean of 4.43 (95% CI: 3.6 to 5.3) and median 4.0 (range 2.25 to 5.75). The agreement was lower with a kappa of 0.63 (95% CI: 0.40 to 0.88). Construct validity was shown by AMSTAR convergence with the results of the global assessment: Pearson's R 0.72 (95% CI: 0.53 to 0.84). For the AMSTAR total score, the limits of agreement were −0.19±1.38. This translates to a minimum detectable difference between reviews of 0.64 ‘AMSTAR points’. Further validation of AMSTAR is needed to assess its validity, reliability and perceived utility by appraisers and end users of reviews across a broader range of systematic reviews.
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              Therapeutic trajectory of hyaluronic acid versus corticosteroids in the treatment of knee osteoarthritis: a systematic review and meta-analysis.

              To compare the efficacy of intraarticular hyaluronic acid with corticosteroids for knee osteoarthritis (OA). Our data sources were Medline, EMBASE, CINAHL, BIOSIS, and the Cochrane database, as well as hand- searched reviews, manuscripts, and supplements. For unpublished data we used author contacts. Randomized trials that reported effects of intraarticular hyaluronic acid versus corticosteroids on knee OA were selected based on inclusion criteria. Two reviewers extracted data independently. Using a random-effects model, we computed effect sizes for pain change from baseline at 2, 4, 8, 12, and 26 weeks. We also performed multivariate analyses accounting for within and between-study covariance. We performed sensitivity analyses for trials that reported intent-to-treat (ITT) analysis and blinding, and directly compared Hyalgan with methylprednisolone. The 7 eligible trials included 606 participants. Five reported ITT analyses. At week 2 the effect size was -0.39 (95% confidence interval [95% CI], -0.65, -0.12) favoring corticosteroids; at week 4 it was -0.01 (95% CI -0.23, 0.21) suggesting equal efficacy. At week 8 the effect size was 0.22 (95% CI -0.05, 0.49) favoring hyaluronic acid, and at week 12 it was 0.35 (95% CI 0.03, 0.66) favoring hyaluronic acid. At week 26 the effect size was 0.39 (95% CI 0.18, 0.59), favoring hyaluronic acid. The multivariate analyses and sensitivity analyses generated consistent results. From baseline to week 4, intraarticular corticosteroids appear to be relatively more effective for pain than intraarticular hyaluronic acid. By week 4, the 2 approaches have equal efficacy, but beyond week 8, hyaluronic acid has greater efficacy. Understanding this trend is useful to clinicians when treating knee OA.
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                Author and article information

                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group
                2045-2322
                12 September 2016
                2016
                : 6
                : 32790
                Affiliations
                [1 ]Arthritis Clinic & Research Center, Peking University People’s Hospital, Peking University , Beijing, China
                Author notes
                [*]

                These authors contributed equally to the work.

                Article
                srep32790
                10.1038/srep32790
                5018721
                27616273
                ed7cc22a-201d-4dd3-b261-8603708474a3
                Copyright © 2016, The Author(s)

                This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

                History
                : 18 December 2015
                : 09 August 2016
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