Objective. The Arthritis, Diet, and Activity Promotion Trial (ADAPT) was a randomized, single-blind clinical trial lasting 18 months that was designed to determine whether long-term exercise and dietary weight loss are more effective, either separately or in combination, than usual care in improving physical function, pain, and mobility in older overweight and obese adults with knee osteoarthritis (OA).Methods. Three hundred sixteen communitydwelling overweight and obese adults ages 60 years and older, with a body mass index of >28 kg/m 2 , knee pain, radiographic evidence of knee OA, and self-reported physical disability, were randomized into healthy lifestyle (control), diet only, exercise only, and diet plus exercise groups. The primary outcome was self-reported physical function as measured with the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Secondary outcomes included weight loss, 6-minute walk distance, stair-climb time, WOMAC pain and stiffness scores, and joint space width.Results. Of the 316 randomized participants, 252 (80%) completed the study. Adherence was as follows: for healthy lifestyle, 73%; for diet only, 72%; for exercise only, 60%; and for diet plus exercise, 64%. In the diet plus exercise group, significant improvements in selfreported physical function (P < 0.05), 6-minute walk distance (P < 0.05), stair-climb time (P < 0.05), and knee pain (P < 0.05) relative to the healthy lifestyle group were observed. In the exercise group, a significant improvement in the 6-minute walk distance (P < 0.05) was observed. The diet-only group was not significantly different from the healthy lifestyle group for any of the functional or mobility measures. The weight-loss groups lost significantly (P < 0.05) more body weight (for diet, 4.9%; for diet plus exercise, 5.7%) than did the healthy lifestyle group (1.2%). Finally, changes in joint space width were not different between the groups.Conclusion. The combination of modest weight loss plus moderate exercise provides better overall improvements in self-reported measures of function and pain and in performance measures of mobility in older overweight and obese adults with knee OA compared with either intervention alone.Arthritis is the leading cause of physical disability among older adults, affecting more than 70 million Americans, of whom the majority are women (1-4). The joint damage and chronic pain from osteoarthritis (OA), the most common form of arthritis, lead to muscle atrophy, decreased mobility, poor balance, and, eventually, physical disability (5-8). Traditional therapies include pharmacologic, surgical, and exercise interventions. Pharmacologic therapy includes the use of antiinflammatory medications that have potentially serious long-term side effects (9,10). Recent evidence also casts doubt as to the effectiveness of arthroscopic surgery for adults with mild to moderate knee OA (11).
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...
Ageing-associated changes that affect articular tissues promote the development of osteoarthritis (OA). Although ageing and OA are closely linked, they are independent processes. Several potential mechanisms by which ageing contributes to OA have been elucidated. This Review focuses on the contributions of the following factors: age-related inflammation (also referred to as ‘inflammaging’); cellular senescence (including the senescence-associated secretory phenotype (SASP)); mitochondrial dysfunction and oxidative stress; dysfunction in energy metabolism due to reduced activity of 5′-AMP-activated protein kinase (AMPK), which is associated with reduced autophagy; and alterations in cell signalling due to age-related changes in the extracellular matrix. These various processes contribute to the development of OA by promoting a proinflammatory, catabolic state accompanied by increased susceptibility to cell death that together lead to increased joint tissue destruction and defective repair of damaged matrix. The majority of studies to date have focused on articular cartilage, and it will be important to determine whether similar mechanisms occur in other joint tissues. Improved understanding of ageing-related mechanisms that promote OA could lead to the discovery of new targets for therapies that aim to slow or stop the progression of this chronic and disabling condition.
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