Objective: To evaluate the effectiveness and safety of viscosupplementation for pain and function in patients with knee osteoarthritis. Design: Systematic review and meta-analysis of randomised trials. Data sources Searches were conducted of Medline, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL) databases from inception to 11 September 2021. Unpublished trials were identified from the grey literature and trial registries. Eligibility criteria for study selection:

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... mised trials comparing viscosupplementation with placebo or no intervention for knee osteoarthritis treatment. Main outcome measures: The prespecified primary outcome was pain intensity. Secondary outcomes were function and serious adverse events. Pain and function were analysed as standardised mean differences (SMDs). The prespecified minimal clinically important between group difference was −0.37 SMD. Serious adverse events were analysed as relative risks. Methods: Two reviewers independently extracted relevant data and assessed the risk of bias of trials using the Cochrane risk of bias tool. The predefined main analysis was based only on large, placebo controlled trials with ≥100 participants per group. Summary results were obtained through a random effects meta-analysis model. Cumulative meta-analysis and trial sequential analysis under a random effects model were also performed. Results: 169 trials provided data on 21 163 randomised participants. Evidence of small study effects and publication biases was observed for pain and function (Egger's tests with P<0.001 and asymmetric funnel plots). Twenty four large, placebo controlled trials (8997 randomised participants) included in the main analysis of pain indicated that viscosupplementation was associated with a small reduction in pain intensity compared with placebo (SMD −0.08, 95% confidence interval −0.15 to −0.02), with the lower bound of the 95% confidence interval excluding the minimal clinically important between group difference. This effect co [...]