The shortage of approaches to modify the course of knee osteoarthritis by delaying either disease progression or disability is due in large part to a critical barrier: factors that bear major responsibility for these outcomes and that might become targets for novel therapy are not well understood. In this application, we propose to apply quantitative gait analysis, to evaluate the role of key forces and joint motion measured during ambulation, and state-of-the-art measures of cartilage loss, function, disability, and stage of pain outcomes, to complete these Aims: 1) evaluate the relationship between the external knee adduction angular impulse during the stance phase of gait and subsequent cartilage loss over 4 years;2) evaluate the relationship between dynamic sagittal plane (flexion-extension) knee motion during gait and subsequent worsening of physical function and disability over 4 years;3) evaluate the frequency of pain stage progression over 4 years and explore if it is associated with concurrent function decline and disability progression. The study we propose leverages our ongoing cohort study. Baseline and 2-year evaluations of 250 persons with knee OA are funded by the current MCRC and 2 R01s (examining hip muscle strength as well as dynamic instability using quantitative gait analysis). We now propose to add a 4-year evaluation - including MRI acquisition, cartilage thickness and denuded bone area quantification, and function and disability outcome assessment at 4 years - and to derive the gait variables needed for Aims 1 and 2 by computational processing and analysis of baseline and 2-year gait data.
The aims we now propose are unique and could not be completed within the ongoing study's scope of work. Without this leveraging, the study we now propose could not be accomplished in one 5-year period. The components of the proposed study will uniquely position us to identify intervention and prevention targets: the longitudinal design and meaningful duration;strategic assessment, using quantitative gait analysis, of key mechanical factors under the dynamic conditions of the most common human weightbearing activity, coupled with direct, state-of-the-art measurement of cartilage loss (Aim 1);and dynamic assessment of critical elements of knee-level joint function coupled with person-level function and disability outcomes (Aim 2). These findings will inform the knee OA natural history paradigm as well as identify as yet untapped targets for novel strategies to prevent cartilage loss, function decline, and disability progression.

Public Health Relevance

Osteoarthritis (OA) at the knee is a major cause of disability, but few strategies to prevent disease worsening or poor outcome in persons with knee OA exist. We will apply quantitative gait analysis, to evaluate the role of key factors measured during ambulation, and state-of-the-art measures of cartilage loss, function, disability, and stage of pain outcomes. The findings will inform understanding of how knee OA evolves and will identify targets for new therapies to prevent cartilage loss, function decline, and disability progression.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Comprehensive Center (P60)
Project #
1P60AR064464-01
Application #
8501984
Study Section
Special Emphasis Panel (ZAR1-KM (M1))
Project Start
Project End
Budget Start
2013-08-01
Budget End
2014-07-31
Support Year
1
Fiscal Year
2013
Total Cost
$234,949
Indirect Cost
$77,682
Name
Northwestern University at Chicago
Department
Type
DUNS #
005436803
City
Chicago
State
IL
Country
United States
Zip Code
60611
Song, Jing; Chang, Alison H; Chang, Rowland W et al. (2017) Relationship of knee pain to time in moderate and light physical activities: Data from Osteoarthritis Initiative. Semin Arthritis Rheum :
Pellegrini, Christine A; Song, Jing; Semanik, Pamela A et al. (2017) Patients Less Likely to Lose Weight Following a Knee Replacement: Results From the Osteoarthritis Initiative. J Clin Rheumatol :
Gilbert, Abigail L; Lee, Jungwha; Ehrlich-Jones, Linda et al. (2017) A randomized trial of a motivational interviewing intervention to increase lifestyle physical activity and improve self-reported function in adults with arthritis. Semin Arthritis Rheum :
Pellegrini, Christine A; Ledford, Gwendolyn; Hoffman, Sara A et al. (2017) Preferences and motivation for weight loss among knee replacement patients: implications for a patient-centered weight loss intervention. BMC Musculoskelet Disord 18:327
White, Daniel K; Lee, Jungwha; Song, Jing et al. (2017) Potential Functional Benefit From Light Intensity Physical Activity in Knee Osteoarthritis. Am J Prev Med 53:689-696
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
Dunlop, Dorothy D; Song, Jing; Lee, Jungwha et al. (2017) Physical Activity Minimum Threshold Predicting Improved Function in Adults With Lower-Extremity Symptoms. Arthritis Care Res (Hoboken) 69:475-483
Sharma, L; Hochberg, M; Nevitt, M et al. (2017) Knee tissue lesions and prediction of incident knee osteoarthritis over 7 years in a cohort of persons at higher risk. Osteoarthritis Cartilage 25:1068-1075
Chang, A H; Chmiel, J S; Almagor, O et al. (2017) Association of baseline knee sagittal dynamic joint stiffness during gait and 2-year patellofemoral cartilage damage worsening in knee osteoarthritis. Osteoarthritis Cartilage 25:242-248
Sharma, Leena; Chang, Alison H; Jackson, Rebecca D et al. (2017) Varus Thrust and Incident and Progressive Knee Osteoarthritis. Arthritis Rheumatol 69:2136-2143

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