Advances in hyaluronic acid therapy for knee osteoarthritis: monotherapy and combination strategies: an evidenced based review

Several human studies show positive signals, while research methods and sample sizes continue to develop.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Knee osteoarthritis (KOA) is a chronic degenerative joint disease that lead to cartilage loss, inflammation, and disability. Intra-articular hyaluronic acid (HA) is widely used for its viscoelastic, anti-inflammatory, and chondroprotective properties; however clinical outcomes remain inconsistent. Recent studies have explored combining HA with biologic or pharmacologic agents, such as platelet-rich plasma (PRP), corticosteroids (CS), fibrinogen, botulinum toxin A, polydeoxyribonucleotide (PDRN), and stem cells, to enhance efficacy through multimodal mechanisms. Despite this, the comparative benefits and safety profiles of these emerging strategies remain unclear. This review aims to evaluate the clinical efficacy of intra-articular HA, used either alone or in combination with adjunctive agents, for the management of KOA. A comprehensive literature search was conducted across PubMed, Embase, the Cochrane Library, and Web of Science, covering the period from January 2010 to April 2025. A total of 70 studies were included, comprising 50 randomized controlled trials (RCTs) and 20 meta-analyses. High-quality evidence supports the modest yet clinically significant efficacy of HA monotherapy, especially in the early to moderate stages of KOA. Outcomes appear to be affected by factors such as molecular weight, crosslinking, and injection protocols. Among combination strategies, the com

Evidence level

Several human studies show positive signals, while research methods and sample sizes continue to develop.

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