Intra-articular Hyaluronic Acid Injections: Long-Term Benefits in Early-Stage Knee Osteoarthritis and Older Women

Introduction

Knee osteoarthritis (OA) is a degenerative joint disorder characterized by cartilage degradation, joint pain, stiffness, and functional limitation. It is increasingly prevalent with the global aging demographic and is a leading cause of disability worldwide. Treatment strategies for knee OA aim to alleviate symptoms, improve joint function, and delay progression. Intra-articular hyaluronic acid (HA) injections are widely utilized to restore synovial fluid viscosity, improve lubrication, and modulate intra-articular inflammation. However, clinical efficacy remains debated due to heterogeneity in trial outcomes, with discrepancies potentially arising from factors such as HA molecular weight, OA severity, and patient-specific characteristics.

HA formulations vary by molecular weight: low (approximately 500–730 kDa), medium (800–2000 kDa), and high (>2000 kDa). Higher molecular weight HA is hypothesized to have prolonged joint residence time and potentially enhanced symptomatic benefit, yet may increase local adverse reactions. Clinical evidence on differential efficacy between these formulations remains inconclusive. Patient-reported outcome measures (PROMs), such as the visual analogue scale (VAS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and Lequesne index, are critical to capture the subjective experience of treatment impact but vary widely between studies.