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Identifying Determinants of Rapid Structural and/or Clinical Progression in Knee Osteoarthritis by Quantitative Assessment of Structural Features on Radiographs

Sponsored by National Institutes of Health

$1.9M Funding
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AbstractKnee osteoarthritis (KOA) is a major public health problem that affects ~30 million US adults with increasedmorbidity and premature mortality. KOA has been identified as one of the biggest unmet medical needsbecause there are no FDA-approved treatments available to prevent slow or halt OA progression.Development and evaluation of potential OA treatments has been hampered in part by KOA typically being aslowly progressive disease though progression is variable and some knees undergo rapid structural or clinicalprogression.Feasible high-throughput methods are needed to gain insights as to how to identify rapid progressors. Wehave developed a rapid reproducible and responsive quantitative software tool Quantitative RadiographicSoftware Scores (QROS) to measure minimal joint space width (JSW) fixed JSW (fJSW) variance of 14fJSW locations; degrees of knee alignment/ malalignment; and orientation and roughness of trabecular bonetexture (TBT).The overarching goal of our research is to identify knees at high risk of rapid progression and our core conceptis that quantitative assessment of a novel combination of baseline structural features on radiographs willidentify a group of knees with rapid structural and/or clinical progression in KOA. Our central hypothesis is thatabnormalities of structural features on knee radiographs will be determinants of varying combinations ofworsening rates of structural and/or clinical progression in KOA. Our approach takes advantage of a uniqueopportunity to innovatively assess radiographic features on ~10500 individuals by combining three of thelargest and most racially diverse longitudinal observational studies of individuals with or at risk of developingKOA: the Johnston County Osteoarthritis Project (JoCoOA) the MulticenterOsteoarthritis Study (MOST) andthe Osteoarthritis Initiative (OAI). All three cohorts have fixed flexion weightbearing knee radiographs thatwere acquired with identical protocols over multiple visits and comparable data on demographics KOA riskfactors and WOMAC pain and function.Our specific aims are: 1). To quantitatively assess structural and clinical progression of KOA separately andcombined; 2). To identify the structural determinants of rapid KOA progression; and 3). To determine the knee-specific probability and time to knee replacement (KR) based on structural and clinical determinants.