Abstract
Osteoarthritis (OA) is a prevalent condition that affects nearly 528 million people worldwide, including 23% of the global population aged ⩾40, and is characterized by progressive damage to articular cartilage, which often leads to substantial pain, stiffness, and reduced mobility for affected patients. Pain related to OA is a barrier to maintaining physical activity and a leading cause of disability, accounting for 2.4% of all years lived with disability globally, reducing the ability to work in 66% of US patients with OA and increasing absenteeism in 21% of US patients with OA. The joint most commonly involved in OA is the knee, which is affected in about 60%-85% of all OA cases. The aging population and longer life expectancy, coupled with earlier and younger diagnoses, translate into a growing cohort of symptomatic patients in need of alternatives to surgery. Despite the large number of patients with knee OA (OAK) worldwide, the high degree of variability in patient presentation can lead to challenges in diagnosis and treatment. Multiple society guidelines recommend therapies for OAK, but departures from guidelines by healthcare professionals in clinical settings reflect a discordance between evidence-based treatment algorithms and routine clinical practice. Furthermore, disease-modifying pharmacotherapies are limited, and treatment for OAK often focuses solely on symptom relief, rather than underlying causes. In this narrative review, we summarize the patient journey, analyze current disease burden and nonsurgical therapy recommendations for OAK, and highlight emerging and promising therapies-such as cryoneurolysis, long-acting corticosteroids, and gene therapies-for this debilitating condition.