Non-Surgical Therapies for Knee Osteoarthritis: Current Evidence and Emerging Strategies

Knee osteoarthritis (OA) is a degenerative joint disease characterized by pain, stiffness, and functional impairment. As many patients seek to avoid surgery, a synthesis of conservative treatment options is clinically relevant for evidence-based management.

A structured PubMed literature search was conducted through December 15, 2025. Eligible studies included randomized controlled trials, cohort and case-control studies, systematic reviews, and meta-analyses evaluating nonsurgical interventions for knee OA. Extracted outcomes included pain, function, safety, and comparative effectiveness across reported follow-up durations.

Intra-articular hyaluronic acid (HA) has a favorable safety profile and may delay progression to total knee arthroplasty, though benefits over placebo are modest and guideline recommendations inconsistent. Platelet-rich plasma (PRP) improves pain and function and may outperform HA, although outcomes vary with preparation methods and study quality. Autologous conditioned serum and dextrose prolotherapy demonstrate symptomatic benefit, whereas corticosteroid injections primarily provide short-term relief. Disease-modifying osteoarthritis drugs (DMOADs), including sprifermin, lorecivivint, LNA043, cathepsin-K inhibition, ADAMTS-5 inhibition, and repurposed metabolic agents such as metformin, are emerging investigational strategies with variable structural and symptomatic results. Early evidence suggests mesenchymal stem cell-based therapies may improve outcomes but remain investigational. Core conservative measures, including exercise therapy, physical therapy, and weight reduction, consistently reduce pain and improve function. Assistive devices and valgus bracing provide additional symptomatic and biomechanical benefit. Among device-based interventions, cooled radiofrequency ablation offers durable pain relief compared with HA or corticosteroids, while sustained acoustic medicine and extracorporeal shockwave therapy show functional improvement; evidence for pulsed electromagnetic field therapy is mixed. Topical nonsteroidal anti-inflammatory drugs provide effective analgesia with reduced systemic risk.

Non-surgical management of knee OA should follow a stepwise approach, with rehabilitation and weight optimization as first-line therapy, selective injection- and device-based options for persistent symptoms, and timely surgical referral when disability remains refractory. Future progress will depend on standardized protocols and higher-quality long-term comparative trials to improve treatment selection and disease modification.