The goal of this Career Development Award is to enhance my ability to independently design and analyze studies on the therapeutic benefit of nutrition and exercise in the treatment and prevention of rheumatic diseases. I bring to my current research goals a unique background of training in measurement of physiologic processes and of an understanding for and appreciation of the factors which influence these processes in humans and animals. I have a strong didactic background in nutritional science, immunology and exercise science. The successful pursuit of this goal requires additional training in clinical trial design, epidemiology and biostatistics to complement the basic science I have in nutrition and exercise. In the research plan we propose to investigate a potential nutrition therapy for synovitis and pain in knee osteoarthritis. There is now much evidence indicating subclinical inflammation in osteoarthritis (OA), even in the absence of acute inflammatory flares. Synovial thickening is related to pain in knee OA. Of particular interest to nutritionists are the mediators of inflammation produced by the n-6 and n-3 fatty acids. The prostaglandins from n-6 fatty acids are potent inflammatory mediators, while those from n-3 fatty acids have only weak effects on the immune cells. Studies increasing n-3 fatty acid intake, have provided evidence of plasma increases in n-3 fatty acids and a reduction in inflammatory mediators. With n-3 fatty acid supplementation, favorable effects on symptoms have been shown in rheumatoid arthritis but no studies have looked at osteoarthritis. Epidemiological studies have observed adequate variability in n-3 intakes and blood levels to find a reduced risk in coronary heart disease. We propose to investigate the relation of plasma fatty acid content with synovitis and pain in an ancillary study to the Multicenter Osteoarthritis Study (MOST). Using plasma to assess fatty acids from baseline specimens, we will examine the relation of n-3 fatty acids to measures of OA, synovitis on MRI and pain on WOMAC, cross sectionally at baseline and longitudinally using data from the 30 month examination. Knee osteoarthritis is the most common cause of lower limb disability in developed countries and there are few nonsurgical treatment options. It is a major public health issue with substantial economic impact that will increase as the population ages. Individuals with the disease are eager for nonpharmacological treatments such as a nutrition intervention. ? ? ?
