ong characterized as a wear-and-tear disorder, osteoarthritis (OA) is now understood to have a complex pathophysiology affecting multiple joints and joint structures, as captured by the Osteoarthritis Research Society International definition of OA: "The disease manifests first as a molecular derangement (abnormal joint tissue metabolism) followed by anatomic, and/or physiologic derangements (characterized by cartilage degradation, bone remodeling, osteophyte formation, joint inflammation and loss of normal joint function), that can culminate in illness." 1 Worldwide, an estimated more than 240 million persons have symptomatic, activity-limiting OA, including an estimated more than 32 million in the US. 2,3 The knee and hip are 2 commonly affected joints and are the focus of this Review. Nearly 30% of individuals older than 45 years have radiographic evidence of knee OA, about half of whom have knee symptoms. 4,5 The prevalence of symptomatic, radiographic hip OA is around 10%. 6,7 The lifetime risk of symptomatic knee OA is greater in obese persons (body mass index Ն30) than in nonobese persons (19.7% vs 10.9%). 8 Prior joint trauma, such as anterior cruciate ligament rupture and ankle fracture, increases risk, accounting for 12% of knee OA cases. 9 The prevalence of symptomatic, radiographic knee OA was 11.4% in women and 6.8% in men in one large cohort study 4 and 18.7% in women and 13.5% in men in another large cohort study. 5 Compared with men with OA, women have more severe radiographic findings and symptoms. 10 Older age and female sex are risk factors for hip OA as well as knee OA. In addition, congenital and acquired anatomic abnormalities (eg, hip dysplasia) are risk factors for hip OA. Regarding race, African American and White persons have similar prevalence of hip OA (accounting for race, sex, and body mass index), while African American individuals, especially women, have higher prevalence of knee OA. 5,7 Osteoarthritis leads to substantial cost and mortality. Fortythree percent of the 54 million individuals in the US living with IMPORTANCE Osteoarthritis (OA) is the most common joint disease, affecting an estimated more than 240 million people worldwide, including an estimated more than 32 million in the US. Osteoarthritis is the most frequent reason for activity limitation in adults. This Review focuses on hip and knee OA.OBSERVATIONS Osteoarthritis can involve almost any joint but typically affects the hands, knees, hips, and feet. It is characterized by pathologic changes in cartilage, bone, synovium, ligament, muscle, and periarticular fat, leading to joint dysfunction, pain, stiffness, functional limitation, and loss of valued activities, such as walking for exercise and dancing. Risk factors include age (33% of individuals older than 75 years have symptomatic and radiographic knee OA), female sex, obesity, genetics, and major joint injury. Persons with OA have more comorbidities and are more sedentary than those without OA. The reduced physical activity leads to a 20% higher age-adj...