Osteoarthritis (OA), particularly knee OA, is among the top 15 causes of disability and the main reason for joint replacement at a cost of over $30 billion/year. Knee OA is typically a slowly progressive disorder but for a recently identified subset the disease progresses with dramatic rapidity. These individuals develop more frequent and severe knee pain, and are 16 times more likely to require a total knee replacement.] Since this is a novel observation, we do not yet know whether individuals experiencing [accelerated knee OA (AKOA) is a distinct disease or an accelerated form of knee OA. Determining factors that differentiate or identify AKOA could lead to preventive strategies and uncover therapeutic targets. Our goals are to test if AKOA can be uniquely characterized by: (i) anatomical characteristics associated with injuries and abnormal loading, (ii) biochemical factors that compromise structures (glucose homeostasis, inflammation), (iii) certain types of instigating pathology, and (iiii) distinct pathological processes.] To achieve these goals we propose to perform a nested case-control study with three groups selected from the Osteoarthritis Initiative. The Osteoarthritis Initiative is an outstanding study that conducts annual evaluations; including magnetic resonance images, x- rays, and clinical measurements; of people with or at risk for knee OA. The three groups we propose to examine will be [1) knees that develop AKOA, 2) knees that develop common OA,] and 3) knees with no OA. AKOA will be defined as knees that progress from no radiographic OA at baseline to end-stage OA within 48- months. Common knee OA will be defined as knees with no radiographic OA at baseline but increase in radiographic scoring within 48 months (excluding those defined as AKOA). Finally, no OA will be knees with no radiographic OA and do not progress. We will assess annual MR images in the sample to identify and quantify structural changes in the knee. We will also perform assays to measure [baseline glucose balance and systemic] inflammation. Finally, we will also use serum and urine biomarker data provided by the OAI to measure bone and cartilage turnover. [These findings could lead to preventive strategies and uncover therapeutic targets. Furthermore, the insights generated from this study may generalize to regular knee OA, expanding the overall field.]

Public Health Relevance

Osteoarthritis (OA), particularly knee OA, is a leading cause of physical disability in the United States but yet there are no effective treatments for slowing knee OA progression. Despite OA typically progressing slowly, some individuals experience [accelerated joint deterioration] and this may be an informative group of individuals. Findings from this study [could lead to preventive strategies and uncover therapeutic targets.]

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
5R01AR065977-03
Application #
9245632
Study Section
Skeletal Biology Structure and Regeneration Study Section (SBSR)
Program Officer
Lester, Gayle E
Project Start
2015-04-01
Project End
2019-03-31
Budget Start
2017-04-01
Budget End
2018-03-31
Support Year
3
Fiscal Year
2017
Total Cost
$327,994
Indirect Cost
$116,730
Name
Tufts University
Department
Type
Independent Hospitals
DUNS #
079532263
City
Boston
State
MA
Country
United States
Zip Code
02111
Stout, Alina C; Barbe, Mary F; Eaton, Charles B et al. (2018) Inflammation and glucose homeostasis are associated with specific structural features among adults without knee osteoarthritis: a cross-sectional study from the osteoarthritis initiative. BMC Musculoskelet Disord 19:1
Davis, Julie E; Liu, Shao-Hsien; Lapane, Kate et al. (2018) Adults with incident accelerated knee osteoarthritis are more likely to receive a knee replacement: data from the Osteoarthritis Initiative. Clin Rheumatol 37:1115-1118
Harkey, Matthew S; Price, Lori Lyn; McAlindon, Timothy E et al. (2018) Declining Walking Speed Associates with Increasing Bone Marrow Lesion Volume and Effusion Volume in Individuals with Accelerated Knee Osteoarthritis. Arthritis Care Res (Hoboken) :
Driban, Jeffrey B; McAlindon, Timothy E; Amin, Mamta et al. (2018) Risk factors can classify individuals who develop accelerated knee osteoarthritis: Data from the osteoarthritis initiative. J Orthop Res 36:876-880
Davis, Julie E; Schaefer, Lena F; McAlindon, Timothy E et al. (2018) Characteristics of Accelerated Hand Osteoarthritis: Data from the Osteoarthritis Initiative. J Rheumatol :
Davis, Julie E; Ward, Robert J; MacKay, James W et al. (2018) Effusion-synovitis and infrapatellar fat pad signal intensity alteration differentiate accelerated knee osteoarthritis. Rheumatology (Oxford) :
Davis, Julie E; Harkey, Matthew S; Ward, Robert J et al. (2018) Characterizing the distinct structural changes associated with self-reported knee injury among individuals with incident knee osteoarthritis: Data from the osteoarthritis initiative. Clin Anat 31:330-334
Harkey, Matthew S; Davis, Julie E; Lu, Bing et al. (2018) Diffuse tibiofemoral cartilage change prior to the development of accelerated knee osteoarthritis: Data from the osteoarthritis initiative. Clin Anat :
McAlindon, T; Roberts, M; Driban, J et al. (2018) Incident hand OA is strongly associated with reduced peripheral blood leukocyte telomere length. Osteoarthritis Cartilage 26:1651-1657
Driban, Jeffrey B; Eaton, Charles B; Amin, Mamta et al. (2017) Glucose homeostasis influences the risk of incident knee osteoarthritis: Data from the osteoarthritis initiative. J Orthop Res 35:2282-2287

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