Symptomatic knee osteoarthritis (OA) affects 6% of the U.S. adult population and 12-13% of those ages 60 and over. In elders, OA of the knee and hip are the most common causes of mobility disability and are a leading cause of difficulty with functional tasks and of dependence on others. Medical treatment often fails to provide adequate relief of pain and disability. Inflammation has long been thought to play a role in accelerating progression and contributing to pain in OA. If so, treating it might affect the long term course and impact of OA. The role of systemic inflammation in OA is the focus of this project. While some studies have shown systemic inflammatory mediators are elevated in OA, others have not found a relationship or have suggested that such associations are present because of inadequate adjustment for factors that themselves are associated with inflammation, such as obesity and age. We shall focus on phenotypic and genotypic characterization of systemic inflammation and its mediators to characterize the role of systemic inflammation in the incidence and progression of OA. We will use data from an epidemiologic study of knee OA, the Multicenter Osteoarthritis Study (MOST), a study in which a large number of subjects have repeated knee Mires, permitting assessment of cartilage loss and synovial thickening, an intraarticular site of inflammation. We will perform gadolinium contrast enhanced MRIs in a subgroup to improve visualization of the synovium. We contend that inflammation may relate differently to cartilage loss than to joint pain.
The aims are to: to evaluate the cross sectional and longitudinal relationship of systemic inflammation markers (including markers of phenotype such as CRP and genetic polymorphisms linked to enhanced inflammatory response) with cartilage loss in the knee on MRI and with knee pain: examine whether effects of systemic inflammation are mediated through direct effects on intraarticular inflammation (synovial thickening), leading to indirect effects of systemic inflammation on either pain or cartilage loss;and examine whether effects of aging on cartilage loss are explained, in part, by the rise in inflammatory markers that occurs with age. The combination of a large scale longitudinal study, measures of systemic and local inflammation and a comprehensive characterization of features of knee OA makes it likely that the proposed study will produce unique insights into the relation of inflammation with this major disabling disease.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
5R01AG028359-05
Application #
7898729
Study Section
Special Emphasis Panel (ZAG1-ZIJ-5 (M1))
Program Officer
Dutta, Chhanda
Project Start
2006-09-30
Project End
2012-06-30
Budget Start
2010-07-15
Budget End
2012-06-30
Support Year
5
Fiscal Year
2010
Total Cost
$248,705
Indirect Cost
Name
University of Alabama Birmingham
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
063690705
City
Birmingham
State
AL
Country
United States
Zip Code
35294
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Singh, Jasvinder A; Lewallen, David G (2014) Time trends in the characteristics of patients undergoing primary total knee arthroplasty. Arthritis Care Res (Hoboken) 66:897-906
Sattui, Sebastian E; Singh, Jasvinder A; Gaffo, Angelo L (2014) Comorbidities in patients with crystal diseases and hyperuricemia. Rheum Dis Clin North Am 40:251-78