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In the absence of disease-modifying interventions for knee osteoarthritis (OA), working to prevent the development of knee OA is paramount. Here, we investigate a potential way of preventing the onset of knee OA in a high risk demographic – women with BMI > 30. Data indicate that losing as little as 5 kg or 5% of baseline weight may result in up to a 3-fold reduction in the risk of knee OA in obese women.

The Osteoarthritis Prevention Trial (TOPS) aims to examine the effects of a long term dietary weight loss and exercise program in the prevention of symptomatic and structural knee OA in at-risk females compared to a general health education control. TOPS is an assessor-blinded 4 year randomized clinical trial with staggered enrollment over the course of 7 years. Exercise and weight loss are expected to impact three major areas of knee OA prevention: the biomechanical pathway through decreasing joint load, the inflammatory pathway by lowering inflammatory cytokine activity, and promoting personal psychological growth through the mastery of experiences. These are expected to lower the probability of developing knee OA by reducing subchondral tissue damage, improving self-efficacy, and decreasing cartilage loss and synovitis.

Over 1700 patients at 5 different clinical sites (Brigham and Women’s Hospital, Cleveland Clinic, UNC Chapel Hill, University of Sydney, and Wake Forest University) will be randomized to receive either a diet and exercise regimen or a health education control. For the first 24 months in the diet and exercise group, the regimen will be focused on trying to lose at least 10% of baseline body weight. The physical activity sessions will be conducted at a local facility and led by research staff. The second 24 months will focus on maintaining weight loss and increasing subject self-efficacy through an at-home exercise program. The health education control group will attend informational sessions and receive a membership to a local YMCA or equivalent for all 4 years of the trial.

We will begin enrolling patients at the Brigham in 2021.

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