Improving the Efficacy of Hyaluronic Acid Injections

Knee osteoarthritis (KOA) is a progressive degenerative disease characterized by pain, cartilage loss, and significant functional disability. Intra-articular (IA) hyaluronic acid (HA) has long been a staple in the conservative management of KOA. Its efficacy as a monotherapy is increasingly being questioned in favor of more effective combination therapies. This narrative review examines whether combining IA HA with corticosteroids (CS) or platelet-rich plasma (PRP) improves clinical outcomes and assesses the role of ultrasound guidance (USG) in optimizing delivery in the treatment of KOA. A detailed literature search was conducted across databases including PubMed, Embase, and the ATSU library for studies published through December 2025. A generalized internet search was also conducted. The search targeted keywords related to KOA, HA, PRP, CS, and USG. Evidence suggests that combination therapies provide a more optimal benefit over HA alone. The HA + CS combination provides rapid pain relief, in some studies as early as 24 to 72 hours, by addressing acute inflammation and lubrication of the joint, with pain and functional benefits sustained for up to 26 weeks. While HA + PRP treatment demonstrated a slower onset of action than IA HA + CS, the addition of PRP introduces growth factors that support chondral preservation and can improve pain and function for up to 24 months. Both combination protocols demonstrated favorable safety profiles with minimal adverse events. Furthermore, the use of USG significantly improved needle accuracy over traditional landmark-based injections, reducing failure rates and improving overall therapeutic efficacy. Combining IA HA with CS or PRP is more effective than HA monotherapy for reducing pain and improving mobility in patients with KOA. Despite limitations related to the lack of standardized dosing and frequency, these therapies, particularly when administered under USG, offer a highly effective, value-based alternative to surgical intervention.