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Judit Takacs,1 Judy E Anderson,1,3 Jeff RS Leiter,1,2,4 Peter B MacDonald,2,4 Jason D Peeler1,4 1Department of Human Anatomy and Cell Science, 2Department of Surgery, 3Department of Biological Sciences, University of Manitoba, Winnipeg, Manitoba, Canada; 4Pan Am Clinic, Winnipeg, Manitoba, Canada Background: Knee osteoarthritis (OA) is the most prevalent medical condition in individuals over the age of 65 years, and is a progressive joint degenerative condition with no known cure. Research suggests that there is a strong relationship between knee pain and loss of physical function. The resulting lifestyle modifications negatively impact not only disease onset and progression but also overall health, work productivity, and quality of life of the affected individual. Purpose: The goal of this investigation was to examine the feasibility of using an emerging technology called lower body positive pressure (LBPP) to simulate weight loss and reduce acute knee pain during treadmill walking exercise in overweight individuals with radiographically confirmed symptomatic knee OA. Design: Prospective case series. Methods: Twenty-two overweight individuals with knee OA completed two 20-minute treadmill walking sessions (one full weight bearing and one LBPP supported) at a speed of 3.1 mph, 0% incline. Acute knee pain was assessed using a visual analog scale, and the percentage of LBPP support required to minimize knee pain was evaluated every 5 minutes. Knee Osteoarthritis Outcome Scores were used to quantify knee pain and functional status between walking sessions. The order of testing was randomized, with sessions occurring a minimum of 1 week apart. Results: A mean LBPP of 12.4% of body weight provided participants with significant pain relief during walking, and prevented exacerbation of acute knee pain over the duration of the 20-minute exercise session. Patients felt safe and confident walking with LBPP support on the treadmill, and demonstrated no change in Knee Osteoarthritis Outcome Scores over the duration of the investigation. Conclusion: Results suggest that LBPP technology can be used safely and effectively to simulate weight loss and reduce acute knee pain during weight-bearing exercise in an overweight knee OA patient population. These results could have important implications for the development of future treatment strategies used in the management of at-risk patients with progressive knee OA. Keywords: knee osteoarthritis, knee pain, exercise, lower body positive pressure