Knee osteoarthritis (OA) is a leading cause of chronic disability in the elderly. The natural rate of progression or worsening of knee OA varies; the reasons for this are poorly understood. The influence of impairments in the local, joint-organ-level environment on OA progression rate or on patient-centered physical functioning has received little attention in epidemiologic study. Whether such impairments develop before or after OA onset, they may contribute to subsequent OA progression and/or functional decline. Meniscal tears and malalignment are local impairments which are present in a subset of patients with mild-moderate OA and adversely affect load distribution. Another key element of the local environment is the functional capacity of the cartilage itself, i.e. its ability to withstand and transmit load. Our primary goal is to examine the relationship of meniscal tears and malalignment with compartment-specific tibiofemoral progression and with functional status decline in a cohort of 300 patients with knee OA. Secondarily, we will examine the impact of malalignment, laxity, muscle weakness and proprioception impairment on long-term (0-7 year) outcome. We also propose to measure cartilage deformation after exercise (which may be an in vivo measure of the functional capacity of cartilage) in a pilot study involving a subset of the cohort. A longitudinal, natural history study of knee OA with radiographic and functional outcomes is ongoing, Mechanical Factors in Arthritis of the Knee (MAK), in which time 0, 1.5 (completed) and 3 year (ongoing) evaluations of alignment, laxity, proprioception and strength in 300 subjects are funded. The project proposed here builds upon the infrastructure and results of this study. Support to evaluate the MAK cohort at 5 and 7 years (on the MAK timeline) is sought. The proposed study will provide much needed information regarding local determinants of the natural outcome of knee OA and will help to identify the joint-organ-level factors which should ultimately become the target of intervention, based upon their link to disease progression and/or their link to declining functional status.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
5R01AR048216-03
Application #
6694426
Study Section
Special Emphasis Panel (ZRG1-EDC-3 (01))
Program Officer
Lester, Gayle E
Project Start
2002-03-06
Project End
2006-12-31
Budget Start
2004-01-01
Budget End
2004-12-31
Support Year
3
Fiscal Year
2004
Total Cost
$124,630
Indirect Cost
Name
Northwestern University at Chicago
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
005436803
City
Chicago
State
IL
Country
United States
Zip Code
60611
Chang, A H; Moisio, K C; Chmiel, J S et al. (2015) External knee adduction and flexion moments during gait and medial tibiofemoral disease progression in knee osteoarthritis. Osteoarthritis Cartilage 23:1099-106
Moisio, Kirsten; Chang, Alison; Eckstein, Felix et al. (2011) Varus-valgus alignment: reduced risk of subsequent cartilage loss in the less loaded compartment. Arthritis Rheum 63:1002-9
Chang, Alison; Moisio, Kirsten; Chmiel, Joan S et al. (2011) Subregional effects of meniscal tears on cartilage loss over 2 years in knee osteoarthritis. Ann Rheum Dis 70:74-9
Kothari, Ami; Guermazi, Ali; Chmiel, Joan S et al. (2010) Within-subregion relationship between bone marrow lesions and subsequent cartilage loss in knee osteoarthritis. Arthritis Care Res (Hoboken) 62:198-203
Moisio, Kirsten; Eckstein, Felix; Chmiel, Joan S et al. (2009) Denuded subchondral bone and knee pain in persons with knee osteoarthritis. Arthritis Rheum 60:3703-10
Eckstein, Felix; Hudelmaier, Martin; Cahue, September et al. (2009) Medial-to-lateral ratio of tibiofemoral subchondral bone area is adapted to alignment and mechanical load. Calcif Tissue Int 84:186-94
Eckstein, Felix; Wirth, Wolfgang; Hudelmaier, Martin et al. (2008) Patterns of femorotibial cartilage loss in knees with neutral, varus, and valgus alignment. Arthritis Rheum 59:1563-70
Sharma, Leena; Eckstein, Felix; Song, Jing et al. (2008) Relationship of meniscal damage, meniscal extrusion, malalignment, and joint laxity to subsequent cartilage loss in osteoarthritic knees. Arthritis Rheum 58:1716-26
Torres, L; Dunlop, D D; Peterfy, C et al. (2006) The relationship between specific tissue lesions and pain severity in persons with knee osteoarthritis. Osteoarthritis Cartilage 14:1033-40