| Summary: | Background: A BMI > 25 is the most decisive, albeit modifiable, risk factor for knee osteoarthritis (KOA). This study aimed at assessing the efficacy of intra-articular injections of hybrid hyaluronic acid (HA) complexes (Sinovial<sup>®</sup> H-L) for the treatment of KOA in overweight patients in terms of disease severity, cardiocirculatory capacity, and quality of life. Materials: In this single-site, open-label, prospective trial, 37 patients with symptomatic knee OA were assessed at baseline and 3 months after ultrasound-guided intra-articular injection of hybrid HA complexes (Sinovial<sup>®</sup> H-L). Results: Primary variables displaying a statistically significant improvement after treatment were pain (VAS), disease severity (WOMAC), and cardiopulmonary capacity (6 min walk test). Among secondary variables, quality of life (SF-12) improved significantly, as did analgesic intake for pain control. No statistically significant difference was observed in body fat and muscle mass percentage measured by bioelectrical impedance analysis. Conclusions: Intra-articular hybrid HA injections are significantly effective in improving OA-related disease severity, cardiopulmonary function, and analgesic intake. This supports the role of hybrid HA viscosupplementation as a nonpharmacological treatment to relieve pain, reduce disability, improve quality of life, and limit the risk of polypharmacy in overweight patients with knee OA.
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