Osteoarthritis (OA) is a complex, heterogeneous condition that is the most common cause of disability in the aging population. The hallmarks of the pathophysiology of OA are the breakdown of cartilage in joints and the associated changes in adjacent soft tissue and subchondral bone that lead to debilitating joint symptoms such as pain. The public health impact of OA, especially knee OA, has and will continue to increase dramatically, but there are no FDA-approved disease-modifying OA drugs (DMOADs), i.e., drugs designed to delay or avert the OA-related structural changes to cartilage and bone. Recent advances in magnetic resonance imaging (MRI) have been made, however, that have improved our understanding of the relationship between pathology and the structural changes to cartilage, subchondral bone and the surrounding soft tissues of the joint in OA. The proposed study builds on the strengths of two ongoing studies, the Osteoarthritis Initiative (OAI) and the Pivotal OAI MRI Analyses (POMA), an ancillary proposal to the OAI. The OAI was designed to address the lack of biomarkers for the development and progression of knee OA. Through POMA, we have utilized the OAI MRIs to identify imaging biomarkers of knee OA development and progression up to 48 months prior to the onset of radiographic knee OA (ROA). The overall objective of this proposal is to take advantage of a time-limited opportunity to build on our prior work and leverage the wealth of longitudinal data, including high-resolution MRI imaging at 3 Tesla(T), which has already been accumulated in the OAI. We will be able test whether structural changes detectable by MRI predict the onset of radiographic knee osteoarthritis (ROA) and the development of important clinical outcomes 24 months to 120 months later, and therefore much earlier in the disease course than currently established. A 120-month visit will be added to the OAI for participants with knees that did not have ROA at baseline.
The specific aims are to identify imaging biomarkers of the development of incident radiographic knee OA (ROA) earlier in the disease course; and to identify the association of imaging biomarkers with changes in pain, function and performance associated with the onset of radiographic knee OA. Ultimately, this line of research will help to identify key risk factors for the development of OA and OA structural disease progression, and to identify potential targets for preventative and/or therapeutic interventions.

Public Health Relevance

This study will help to identify treatments to slow the progression of disease. Knee osteoarthritis is a very common and disabling disease. There are no approved potential targets for new treatments to prevent the development of disease or halt disease progression.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
5R01AR066601-03
Application #
9118702
Study Section
Neurological, Aging and Musculoskeletal Epidemiology (NAME)
Program Officer
Lester, Gayle E
Project Start
2014-09-15
Project End
2019-07-31
Budget Start
2016-08-01
Budget End
2017-07-31
Support Year
3
Fiscal Year
2016
Total Cost
$1,556,080
Indirect Cost
$194,540
Name
University of Arizona
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
806345617
City
Tucson
State
AZ
Country
United States
Zip Code
85721
Vina, Ernest R; Kwoh, C Kent (2018) Epidemiology of osteoarthritis: literature update. Curr Opin Rheumatol 30:160-167
Roemer, Frank W; Kwoh, C Kent; Fujii, Tomoko et al. (2018) From Early Radiographic Knee Osteoarthritis to Joint Arthroplasty: Determinants of Structural Progression and Symptoms. Arthritis Care Res (Hoboken) 70:1778-1786
Vina, E R; Ran, D; Ashbeck, E L et al. (2018) Natural history of pain and disability among African-Americans and Whites with or at risk for knee osteoarthritis: A longitudinal study. Osteoarthritis Cartilage 26:471-479
Roemer, Frank W; Kwoh, C Kent; Hayashi, Daichi et al. (2018) The role of radiography and MRI for eligibility assessment in DMOAD trials of knee OA. Nat Rev Rheumatol 14:372-380
Ratzlaff, C; Ashbeck, E L; Guermazi, A et al. (2018) A quantitative metric for knee osteoarthritis: reference values of joint space loss. Osteoarthritis Cartilage 26:1215-1224
Lo, Grace H; Musa, Sarra M; Driban, Jeffrey B et al. (2018) Running does not increase symptoms or structural progression in people with knee osteoarthritis: data from the osteoarthritis initiative. Clin Rheumatol 37:2497-2504
Vina, Ernest R; Ran, Di; Ashbeck, Erin L et al. (2018) Race, sex, and risk factors in radiographic worsening of knee osteoarthritis. Semin Arthritis Rheum 47:464-471
Roth, Melanie; Wirth, Wolfgang; Emmanuel, Katja et al. (2017) The contribution of 3D quantitative meniscal and cartilage measures to variation in normal radiographic joint space width-Data from the Osteoarthritis Initiative healthy reference cohort. Eur J Radiol 87:90-98
Lo-Ciganic, W-H; Floden, L; Lee, J K et al. (2017) Analgesic use and risk of recurrent falls in participants with or at risk of knee osteoarthritis: data from the Osteoarthritis Initiative. Osteoarthritis Cartilage 25:1390-1398
Ruhdorfer, A; Wirth, W; Eckstein, F (2017) Association of knee pain with a reduction in thigh muscle strength - a cross-sectional analysis including 4553 osteoarthritis initiative participants. Osteoarthritis Cartilage 25:658-666

Showing the most recent 10 out of 26 publications