Obesity and osteoarthritis (OA) are intimately related;obesity is a modifiable risk factor for OA and weight loss may offer a potential non-invasive therapy for disease prevention and for slowing progression in obese individuals. To date, however, the effects of weight loss on joint structure and cartilage biochemistry, in particular in the early stages of disease, have been inconclusive;studies have been limited by short-term follow-up and have focused on advanced disease stages. The proposed study utilizes imaging data from the Osteoarthritis Initiative, which facilitates the assessment of early disease stages i conjunction with the longitudinal evolution of OA;using this unique and rich dataset, this study aims to determine the impact of weight loss on the biochemical and morphologic changes at the knee joint and their relationship with physical activity and clinical symptoms over a period of 8 years. We will use MRI T2 relaxation time measurements, which assess cartilage collagen integrity and water content as well as semi-quantitative morphological MR grading. We will comprehensively investigate the whole knee joint including the cartilage, meniscus, bone marrow, and joint space in subjects with weight loss and controls with constant weight over 8 years. Our proposed project has 3 Specific Aims: (I) To determine whether weight loss in overweight and obese individuals without OA (but risk factors for OA) as well as with OA protects against the development and progression of cartilage biochemical and morphological joint degeneration, and improves clinical symptoms over 8 years. (II) To determine which methods for weight loss (changes in diet, increased physical activity, surgery) are associated with slower progression of structural and biochemical joint degeneration as well as alleviation of clinical symptoms. (III) To identify baseline characteristics of patients whose weight loss is associated with slower progression of degenerative disease. The proposed project will, for the first time, assess whether weight loss in overweight and obese individuals may prevent the onset of OA and whether it may halt the progression of disease. By studying 640 subjects stratified by varied magnitudes of weight loss and varied levels of joint morphology, this proposal would comprehensively assess changes in joint morphology, cartilage biochemistry, and clinical symptoms in response to weight loss over 8 years. From this study, we expect to establish subject-specific guidelines for weight loss therapy in response to OA that are contingent upon the degree of pre-existing degenerative disease and initial weight. Prevention is currently the key intervention in OA and we strongly believe that our study will greatly contribute to streamlining and optimizing clinical practice of OA prevention

Public Health Relevance

Obesity and osteoarthritis are major public health concerns, which are closely intertwined;while weight loss alleviates biomechanical stresses on the joint, its precise impact on cartilage biochemistry and the knee joint structure has yet to be determined. In order to provide subject-specific recommendations for weight loss as a preventative treatment, it is critical to gain information on (i) the amount of weight loss require, (ii) the degree of pre-existing degenerative disease, (iii) the baseline body habitus, and (iv) the interplay between weight changes and associated factors such as physical activity. Using the unique Osteoarthritis Initiative Cohort will allow us to address all of these concerns for the firs time by comprehensively assessing knee biochemistry and structure over a period of 8 years and determining the impact of weight loss on the onset and progression of osteoarthritis.

National Institute of Health (NIH)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Research Project (R01)
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Neurological, Aging and Musculoskeletal Epidemiology (NAME)
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Lester, Gayle E
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University of California San Francisco
Schools of Medicine
San Francisco
United States
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