Comparative Efficacy and Safety of Platelet-Rich Plasma Alone Versus Platelet-Rich Plasma Combined with Hyaluronic Acid for Knee Osteoarthritis: A Systematic Review

Abstract

Eric Lorenzeto Cardoso, Thiago Cavalcante Ribeiro, Douglas de Melo Moura, Gabriel de Castro Monteiro, Helena Maria Mendes Marques, Gabriel Ricardo de Araujo Ruivo, Edward Rodrigues De Oliveira Filho, Frederico Tannus de Almeida, Sylvane Fernandes Santos Oliveira and Karollyne da Silva Morais

Background: Knee osteoarthritis is a prevalent degenerative joint disease characterized by pain, stiffness, functional limitation, and progressive impairment in quality of life. Intra-articular platelet-rich plasma (PRP) and hyaluronic acid (HA) are widely used conservative injectable therapies, and their combination has been proposed to integrate the biological effects of platelet-derived mediators with the viscoelastic and lubricating properties of HA.

Objective: This systematic review aimed to evaluate the efficacy and safety of PRP alone compared with PRP combined with HA in patients with knee osteoarthritis, considering pain, physical function, stiffness, patient-reported outcomes, adverse events, and follow-up duration across available clinical studies.

Methods: Clinical studies published in English between 2011 and 2026 were reviewed. Eligible studies included randomized controlled trials, prospective clinical studies, retrospective comparative studies, and experimental clinical studies evaluating PRP alone, HA alone, PRP+HA, or related injectable comparators in knee osteoarthritis. The main outcomes were pain, physical function, stiffness, quality of life, treatment response, adverse events, and methodological quality. Because of heterogeneity in study design, PRP preparation, HA formulation, injection protocol, comparator groups, and follow-up duration, the findings were synthesized qualitatively.

Results: Twenty-five clinical studies were included. PRP-based interventions were consistently associated with improvement in pain and physical function, with a favorable safety profile. PRP alone was frequently superior to HA, particularly at medium- and long-term follow-up, although this finding was not uniform across all studies. Studies comparing PRP+HA with HA alone generally favored the combined intervention, suggesting that the addition of PRP may enhance the clinical effect of viscosupplementation. However, direct comparisons between PRP+HA and PRP alone showed heterogeneous results, with no consistent evidence that the combined treatment is superior to PRP monotherapy. Most adverse events were mild and transient, including post-injection pain, swelling, stiffness, or local discomfort.

Conclusion: PRP-based intra-articular therapy appears to be effective and safe for symptomatic knee osteoarthritis. PRP+HA may offer clinical advantages over HA alone, but its superiority over PRP alone remains uncertain. Therefore, PRP+HA should be interpreted as a promising combined approach rather than a definitively superior alternative to PRP monotherapy.

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