https://doi.org/10.4081/ejtm.2026.15626
Clinical efficacy of 4.4 mL single-dose intra-articular cross-linked hyaluronic acid injection in patients with knee osteoarthritis
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Published: 6 August 2026
Osteoarthritis (OA) is a degenerative joint disease with increasing prevalence due to population aging. Conservative management of knee OA has traditionally focused on pain control, with intra-articular injections widely used for targeted local therapy. This study evaluated the clinical efficacy of a single 4.4 mL intra-articular injection of cross-linked hyaluronic acid compared with hylastan SGL-80 (4 mL) in patients with knee OA. In this interventional cohort study, 120 patients with grade III knee OA (Outerbridge) were allocated to two groups: Group 1 (UP; n=60) received 4.4 mL cross-linked hyaluronic acid, and Group 2 (Normal; n=60) received hylastan SGL-80/4 mL. All patients followed a 15-day NSAID protocol before injection and had no prior knee injections within 6 months. Outcomes were assessed using VAS, KOOS, and SF-12 at baseline and up to 6 months. Analgesic use, complications, and VAS–KOOS correlations were evaluated. Both groups showed a low complication rate (5%). Pain reduction over 6 months was significantly greater in Group 1 (VAS 6.93 to 2.32) than in Group 2 (6.44 to 3.52; p=0.030). Group 1 demonstrated superior KOOS (p=0.017), SF-12 scores (p=0.021), and reduced anti-inflammatory drug use (p=0.026). VAS–KOOS correlation confirmed greater clinical improvement in Group 1 at 180 days (p=0.031). A single 4.4 mL intra-articular injection of cross-linked hyaluronic acid provides significant and sustained improvement in pain, function, and quality of life in patients with knee OA.
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Ethics Approval
CRediT authorship contribution
Conceptualization, Luigi Meccariello and Giuseppina Casolaro; methodology, Luigi Meccariello, Clemente Villari and Jacopo Conteduca; validation, Luigi Meccariello, Clemente Villari and Jacopo Conteduca..; formal analysis, Luigi Meccariello and Giuseppe Rovere; investigation, Luigi Meccariello Lawrance Camarda.; software development, Giuseppina Casolaro and Giuseppe Rovere; data curation, Giuseppe Rovere and Luigi Meccariello.; writing—original draft preparation, Luigi Meccariello and Giuseppe rovere; writing—review and editing, Luigi Meccariello and Giuseppe Rovere; visualization, Lawrance Camarda; supervision, Luigi Meccariello; resource management and project administration, Giuseppina Casolaro.
All authors have read and agreed to the published version of the manuscript.
Supporting Agencies
Data Availability Statement
The datasets generated during the current study are available from the corresponding author on reasonable request.
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