Enhanced Synovial Fluid Rheology in Moderate Knee Osteoarthritis Through Combined Intra-Articular Hyaluronic Acid and Multimodal Physiotherapy: A Monocentric Observational Study

Abstract

Background: Knee osteoarthritis (KOA) is a degenerative joint disorder marked by cartilage degradation, synovial inflammation, and altered synovial fluid (SF) rheology, resulting in pain and impaired joint function. Intra-articular hyaluronic acid (IA-HA) injections aim to restore SF viscoelasticity and improve lubrication; however, their efficacy may be potentiated when combined with physiotherapy (PT). This monocentric observational study evaluated whether the addition of a multimodal PT program to IA-HA therapy enhances SF rheologic properties compared to IA-HA alone. Methods: A total of 52 patients (aged 47–61) with radiographically confirmed moderate KOA (Kellgren–Lawrence grade 2) were enrolled. Patients were assigned to a pilot group (PG; n = 37) receiving IA-HA (Kombihylan®, 3 MDa) combined with a multimodal PT protocol, or a control group (CG; n = 15) receiving IA-HA alone. The PT program included ten sessions of transcutaneous electrical nerve stimulation, low-level laser therapy, therapeutic ultrasound, progressive exercise, and cryotherapy. SF samples were collected immediately after the first injection and again at six weeks, then analyzed rheologically using the Kinexus Pro+ rheometer. Viscosity parameters were assessed via steady and oscillatory shear tests. Results: At baseline, both groups demonstrated comparable SF viscosity profiles. After six weeks, the PG exhibited significantly higher shear viscosity values across all measured percentiles and reduced variability in rheological parameters, suggesting a more stable intra-articular milieu. Rheometric analysis indicated enhanced SF viscoelasticity, potentially mediated by reduced inflammation and stimulation of endogenous HA synthesis. In contrast, the CG showed inconsistent viscosity changes, reflecting variable responses to IA-HA monotherapy. Conclusions: Combining IA-HA with multimodal PT significantly improves SF rheological properties in moderate KOA patients compared to IA-HA alone. These findings support the role of mechanical stimulation in enhancing joint lubrication and homeostasis, offering a more consistent and effective approach to viscosupplementation.