Project 434140

IMPORTANCE By 2041, over 10 million Canadians will have osteoarthritis (OA), with the knee most often affected. Knee OA causes long-term pain and immobility. It damages all tissues in and around a joint. About half of people with knee OA will decline toward disability, some very rapidly. At diagnosis, we cannot predict who will experience steady disease, versus those on a fast path to disability. Our goal is to predict knee OA worsening so that we target treatment to those who need it the most. In-depth movement analysis shows that the torque rotating the lower leg into a bow-legged position at the knee (called the knee adduction moment (KAM)) predicts worsening knee OA - but only people who are obese. The reason why obesity heightened the effect of KAM is unknown. We believe obesity creates inflammation and changes the way our immune system fights off disease. OBJECTIVES To figure out how KAM and obesity work together to worsen knee OA, we will determine if: 1) Obesity-related alterations in tissue quality, inflammation and immunity relate to tissue function for cartilage and muscle. 2) The combination of KAM with poor cartilage function predicts cartilage loss over 3 y. 3) Pain, mobility and function are related with obesity-related inflammation and immune responses. METHOD In 135 people with knee OA, at baseline and 3 y we will use magnetic resonance imaging (MRI) to measure the quantity and quality of cartilage and muscle. We will use MRI to assess cartilage function (changes in cartilage thickness after walking) and a strength-testing machine to assess muscle function. Every 9 months for 3 y, we will collect blood to measure inflammation and immune function; analyze walking; and measure pain, mobility and function. OUTCOMES By examining how KAM and obesity work together to worsen knee OA, we will understand why some with knee OA remain stable, while others get worse. This work is essential to targeting treatment for those facing rapid decline.