Intra-Articular Hyaluronic Acid for Knee Osteoarthritis: A Systematic Umbrella Review.

to evaluate the efficacy, safety, and cost-effectiveness of intra-articular hyaluronic acid (IAHA) in treating osteoarthritis (OA), considering innovations in formulations, comparative outcomes, and variability in guidelines. This review aims to synthesize evidence supporting the role of IAHA in multimodal treatment strategies. A general, narrative, umbrella review of systematic reviews and meta-analyses was conducted. Clinical practice recommendations and guidelines for IAHA use were also reviewed and evaluated. A comprehensive search was conducted across the main medical data sources. Inclusion criteria focused on studies evaluating the efficacy, safety, and impact of IAHA. Key outcomes included pain reduction (e.g., WOMAC, VAS), functional improvement, safety, and cost-effectiveness. IAHA showed moderate efficacy in pain relief and functional improvement, especially in early-to-moderate OA. The results indicate that hybrid formulations and combination therapies show better clinical outcomes, with expanded efficacy and potential chondroprotection. However, heterogeneity between studies was noted, reflecting variability in patient populations and intervention protocols. International guidelines varied significantly, with some opposing routine use (e.g., AAOS, NICE) and others endorsing IAHA more or less conditionally (e.g., ESCEO, OARSI). IAHA remains a treatment modality in the arsenal of selected populations of people with OA, especially for early and moderate disease. High-quality, standardized studies are still needed to refine IAHA's role and establish personalized guidelines for individual patients. A concerted effort to harmonize global recommendations and economic strategies, such as tiered pricing, can increase equitable access and optimize IAHA's integration of multimodal treatment for OA.