Effects of intra-articular hyaluronic acid injections on pain and function in patients with knee osteoarthritis: An umbrella review of systematic reviews and meta-analyses of randomized placebo-controlled trials
Highlights
• The majority of systematic reviews indicate that intra-articular injections of hyaluronic acid are efficacious in knee osteoarthritis.
• All high-quality reviews report significant benefits of intra-articular hyaluronic acid injections on pain and function.
• Discrepancies in the conclusions of reviews are linked to concerns regarding inclusion criteria and clinical relevance.
• Standardized review methods are needed to clarify the effectiveness of intra-articular hyaluronic acid injections.
Abstract
Introduction
Knee osteoarthritis is a prevalent and disabling condition characterized by pain and functional impairment. Intra-articular hyaluronic acid injections are widely used for symptom relief, but their efficacy remains debated due to conflicting conclusions across systematic reviews and meta-analyses. This umbrella review assesses the symptomatic efficacy of intra-articular hyaluronic acid based on evidence reported by previously conducted systematic reviews and meta-analyses, identifies factors contributing to discrepancies in findings, and summarizes consistent outcome trends.
Methods
This umbrella review followed the Cochrane guidelines for overviews of reviews and adhered to the PRIOR reporting checklist. A systematic search was conducted in Medline (Ovid), the Cochrane Database of Systematic Reviews (Ovid CDSR), and Embase, using a predefined Population/Intervention/Comparator/Outcome/Study design (PICOS) framework. Systematic reviews of randomized controlled trials evaluating the efficacy of intra-articular hyaluronic acid on pain and/or function compared with placebo were included. Exclusion criteria were systematic reviews that included both randomized controlled trials and non-randomized controlled trials without separate synthesis of data from the former, scoping reviews, abstracts, commentaries, or narrative reviews. Two independent reviewers screened titles/abstracts, and full texts, resolving disagreements by consensus. Risk of bias was assessed using the AMSTAR-2 checklist, classifying systematic reviews as high, moderate, low, or critically low quality.
Results
Twenty-two systematic reviews were included, with AMSTAR-2 quality ratings as follows: four high, one moderate, three low, and fourteen critically low. The majority (20/22) reported statistically significant beneficial effects of intra-articular hyaluronic acid injections on pain and function. However, according to the interpretation of their authors, fifteen systematic reviews concluded positively, three provided mixed interpretations, and four concluded negatively. All five of the reviews of high or moderate quality reported statistically significant beneficial effects, but with three concluding positively and two negatively. Negative or mixed conclusions were primarily attributed to restrictive inclusion criteria (e.g., analyses only of large trials, minimum patient numbers, long follow-up periods) and challenges in interpreting clinical relevance.
Conclusion
Most systematic reviews and all high-quality systematic reviews support the symptomatic efficacy of intra-articular hyaluronic acid in knee osteoarthritis. Negative interpretations arise when restrictive inclusion criteria challenge the clinical relevance of results. However, given the methodological limitations, variability in review quality, and inconsistent interpretations, the overall certainty of evidence remains limited. These findings highlight the need for standardized methodologies in systematic reviews to provide clearer guidance for clinical practice.
PROSPERO registration CRD42024625696.
Highlights
• The majority of systematic reviews indicate that intra-articular injections of hyaluronic acid are efficacious in knee osteoarthritis.
• All high-quality reviews…
Aims
This umbrella review synthesized evidence from systematic reviews and meta-analyses of randomized controlled trials (RCTs) to assess the effectiveness of…
Introduction: We previously reported a high prevalence of biochemical osteomalacia among apparently healthy Arab adolescents using combined mineralization markers.