Knee osteoarthritis (OA) is associated with substantial pain and disability. The course of knee OA is variable gaps in knowledge of determinants of the natural history of knee OA relate in part to the complexity of investigation. A widely accepted paradigm views knee OA severity as a result of local neuromechanical factors, acting against a background of susceptibility determining systemic factors (e.g. age related, genetic). The neuromechanical status of the knee is theoretically determined by both aspects of structure (especially alignment and laxity) and joint protecting neuromuscular reflexes (requiring joint position sense and muscle contraction). Impairments in these factors result in increased, suboptimally distributed load transmitted to the articular surface, and we suspect are associated with accelerated disease progression. We propose here to test the hypothesis that neuromechanical factors, malalinment, increased laxity, proprioception deficit, and muscle weakness are associated with more rapid progression of knee OA.
Our specific aims are: 1) to measure in 300 symptomatic, tibiofemoral knee OA patients with definite osteophytes, at baseline, 18 months and 36 months, each of the neuromechanical variables noted; 2) to assess change in functional status, the primary outcome, using the Western Ontario and McMaster University OA Index Physical Function scale, and radiographic status by measuring joint space width with a magnifying lens fitted with a graticule, from the standing semi-flexed radiograph; and 3) to analyze the contribution of each of the neuromechanical factors to outcome, while controlling for potentially confounding variables, using analytic methods that allow data from both knees to be considered. We believe that the results of this study will delineate the specific events that caus progression of knee OA, allow correct interpretation of therapeutic trial results, and facilitate early, cost-effective intervention in neuromechanical subsets at particular risk for decline.

Project Start
2000-12-01
Project End
2002-11-30
Budget Start
Budget End
Support Year
18
Fiscal Year
2001
Total Cost
$174,159
Indirect Cost
Name
Northwestern University at Chicago
Department
Type
DUNS #
005436803
City
Chicago
State
IL
Country
United States
Zip Code
60611
Poornima, I G; Shields, K; Kuller, L H et al. (2018) Associations of osteoprotegerin with coronary artery calcification among women with systemic lupus erythematosus and healthy controls. Lupus :961203317751060
Demirci, F Yesim; Wang, Xingbin; Morris, David L et al. (2017) Multiple signals at the extended 8p23 locus are associated with susceptibility to systemic lupus erythematosus. J Med Genet 54:381-389
Demirci, F Yesim; Wang, Xingbin; Kelly, Jennifer A et al. (2016) Identification of a New Susceptibility Locus for Systemic Lupus Erythematosus on Chromosome 12 in Individuals of European Ancestry. Arthritis Rheumatol 68:174-83
Zhao, Jian; Giles, Brendan M; Taylor, Rhonda L et al. (2016) Preferential association of a functional variant in complement receptor 2 with antibodies to double-stranded DNA. Ann Rheum Dis 75:242-52
Kottyan, Leah C; Zoller, Erin E; Bene, Jessica et al. (2015) The IRF5-TNPO3 association with systemic lupus erythematosus has two components that other autoimmune disorders variably share. Hum Mol Genet 24:582-96
Parker, Ben; Urowitz, Murray B; Gladman, Dafna D et al. (2015) Impact of early disease factors on metabolic syndrome in systemic lupus erythematosus: data from an international inception cohort. Ann Rheum Dis 74:1530-6
Martins, M; Williams, A H; Comeau, M et al. (2015) Genetic association of CD247 (CD3?) with SLE in a large-scale multiethnic study. Genes Immun 16:142-50
Bernatsky, Sasha; Ramsey-Goldman, Rosalind; Joseph, Lawrence et al. (2014) Lymphoma risk in systemic lupus: effects of disease activity versus treatment. Ann Rheum Dis 73:138-42
Lertratanakul, Apinya; Wu, Peggy; Dyer, Alan R et al. (2014) Risk factors in the progression of subclinical atherosclerosis in women with systemic lupus erythematosus. Arthritis Care Res (Hoboken) 66:1177-85
Kaiser, Rachel; Tang, Ling Fung; Taylor, Kimberly E et al. (2014) A polymorphism in TLR2 is associated with arterial thrombosis in a multiethnic population of patients with systemic lupus erythematosus. Arthritis Rheumatol 66:1882-7

Showing the most recent 10 out of 248 publications