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Identifying determinants of rapid structural and/or clinical progression in knee osteoarthritis by quantitative assessment of structural features on radiographs

Award Number: R01AR080742
ORGANIZATION: NATIONAL INSTITUTE OF ARTHRITIS & MUSCULOSKELETAL & SKIN DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/12/2022
PERIOD OF PERFORMANCE END DATE: 06/30/2027

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Identifying determinants of rapid structural and/or clinical progression in knee osteoarthritis by quantitative assessment of structural features on radiographs - Abstract Knee osteoarthritis (KOA) is a major public health problem that affects ~30 million US adults, with increased morbidity and premature mortality. KOA has been identified as one of the biggest unmet medical needs because 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 a slowly progressive disease, though progression is variable and some knees undergo rapid structural or clinical progression. Feasible high-throughput methods are needed to gain insights as to how to identify rapid progressors. We have developed a rapid, reproducible, and responsive quantitative software tool, Quantitative Radiographic Software Scores (QROS), to measure minimal joint space width (JSW), fixed JSW (fJSW), variance of 14 fJSW locations; degrees of knee alignment/ malalignment; and orientation and roughness of trabecular bone texture (TBT). The overarching goal of our research is to identify knees at high risk of rapid progression, and our core concept is that quantitative assessment of a novel combination of baseline structural features on radiographs will identify a group of knees with rapid structural and/or clinical progression in KOA. Our central hypothesis is that abnormalities of structural features on knee radiographs will be determinants of varying combinations of worsening rates of structural and/or clinical progression in KOA. Our approach takes advantage of a unique opportunity to innovatively assess radiographic features on ~10,500 individuals by combining three of the largest and most racially diverse longitudinal observational studies of individuals with or at risk of developing KOA: the Johnston County Osteoarthritis Project (JoCoOA), the MulticenterOsteoarthritis Study (MOST), and the Osteoarthritis Initiative (OAI). All three cohorts have fixed flexion, weightbearing knee radiographs that were acquired with identical protocols over multiple visits, and comparable data on demographics, KOA risk factors, and WOMAC pain and function. Our specific aims are: 1). To quantitatively assess structural and clinical progression of KOA, separately and combined; 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.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $560,362 )
2025	2025	UNIVERSITY OF ARIZONA	845 N PARK AVE RM 538	TUCSON	AZ	85721	PIMA	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	4	9/15/2025	NON-COMPETING CONTINUATION	$560,362
														Subtotal = $560,362

Issue Date FY: 2024 ( Subtotal = $687,054 )
2024	2024	UNIVERSITY OF ARIZONA	845 N PARK AVE RM 538	TUCSON	AZ	85721	PIMA	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	3	7/26/2024	NON-COMPETING CONTINUATION	$687,054
2024	2023	UNIVERSITY OF ARIZONA	845 N PARK AVE RM 538	TUCSON	AZ	85721	PIMA	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	2	10/26/2023	SUPPLEMENT FOR EXPANSION	$0
2024	2023	UNIVERSITY OF ARIZONA	845 N PARK AVE RM 538	TUCSON	AZ	85721	PIMA	USA	Arthritis, Musculoskeletal and Skin Diseases Research	002	2	7/29/2024	SUPPLEMENT FOR EXPANSION	$0
														Subtotal = $687,054

Issue Date FY: 2023 ( Subtotal = $1,112,408 )
2023	2023	UNIVERSITY OF ARIZONA	845 N PARK AVE RM 538	TUCSON	AZ	85721	PIMA	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	2	7/14/2023	NON-COMPETING CONTINUATION	$710,394
2023	2023	UNIVERSITY OF ARIZONA	845 N PARK AVE RM 538	TUCSON	AZ	85721	PIMA	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	2	9/7/2023	SUPPLEMENT FOR EXPANSION	$402,014
														Subtotal = $1,112,408

Issue Date FY: 2022 ( Subtotal = $738,879 )
2022	2022	UNIVERSITY OF ARIZONA	888 N EUCLID AVE RM 510	TUCSON	AZ	85719	PIMA	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	1	8/12/2022	NEW	$738,879
														Subtotal = $738,879

Grand Total All Awards = $3,098,703

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Identifying determinants of rapid structural and/or clinical progression in knee osteoarthritis by quantitative assessment of structural features on radiographs

Award Number: R01AR080742

ORGANIZATION: NATIONAL INSTITUTE OF ARTHRITIS & MUSCULOSKELETAL & SKIN DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 08/12/2022

PERIOD OF PERFORMANCE END DATE: 06/30/2027

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