Most of what is known about osteoarthrits (OA) has been derived from clinical studies that have focused on the latter stages of this disease, very little is known about its onset and early progression, and by the time its diagnosed, pain and irreparable cartilage damage are present. The mechanism that produces the onset of OA is unclear, it requires time to progress, and the tools necessary to measure the early changes in the biomechanical and biological behavior of articular cartilage have only become available recently. This investigation will be a case-control study of a relatively homogenous group of subjects that can be identified at the time of index anterior cruciate ligament (ACL) trauma and are at significant risk for the post-traumatic onset of OA. The primary aim of the study will be to measure the temporal changes in the concentrations of the biomarkers of articular cartilage metabolism obtained from synovial fluid samples and joint space width narrowing (a validated indicator of progression of OA). These measurements will be made in subjects that plan to undergo ACL reconstruction immediately before surgery, and in matched control subjects with normal knees at the time of recruitment. Measurements will be repeated at the follow-up intervals of 12, 24, and 48-months. These data will be used to test the primary hypothesis: synovial fluid biomarker levels of articular cartilage metabolism (selected to evaluate Type II collagen and proteoglycan) are associated with narrowing of the tibiofemoral joint space. Disruption of the ACL leads to a dramatic increase in anterior-posterior (A-P) knee laxity, joint instability, and although reconstruction of this ligament attempts to re-establish normal joint biomechanics, it often results in an abnormal increase of A-P knee laxity during healing. One mechanism by which ACL injury and reconstruction leads to OA may be explained by a self-perpetuating process in which structural changes within the ACL graft produce increases in A-P knee laxity, abnormal articular cartilage contact stress, abnormal cartilage metabolism, abnormal articular cartilage properties, and eventually loss of this structure. This serves as the basis for our exploratory hypothesis: the relationship between synovial fluid biomarkers of articular cartilage metabolism and narrowing of the tibiofemoral joint space can be explained by increases in A-P knee laxity during healing. This investigation is important because it will validate the use of synovial fluid biomarkers for the study of early progression of post-traumatic OA and provide insight into the relationship between the altered knee biomechanics associated with ACL reconstruction and progression of OA. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
5R01AR051477-05
Application #
7417612
Study Section
Special Emphasis Panel (ZRG1-MOSS-H (01))
Program Officer
Tyree, Bernadette
Project Start
2004-08-11
Project End
2010-10-31
Budget Start
2008-05-01
Budget End
2010-10-31
Support Year
5
Fiscal Year
2008
Total Cost
$321,325
Indirect Cost
Name
University of Vermont & St Agric College
Department
Orthopedics
Type
Schools of Medicine
DUNS #
066811191
City
Burlington
State
VT
Country
United States
Zip Code
05405
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Tourville, Timothy W; Poynter, Matthew E; DeSarno, Michael J et al. (2015) Relationship between synovial fluid ARGS-aggrecan fragments, cytokines, MMPs, and TIMPs following acute ACL injury: A cross-sectional study. J Orthop Res 33:1796-803
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Tourville, Timothy W; Johnson, Robert J; Slauterbeck, James R et al. (2013) Relationship between markers of type II collagen metabolism and tibiofemoral joint space width changes after ACL injury and reconstruction. Am J Sports Med 41:779-87
Beynnon, Bruce D; Johnson, Robert J; Naud, Shelly et al. (2011) Accelerated versus nonaccelerated rehabilitation after anterior cruciate ligament reconstruction: a prospective, randomized, double-blind investigation evaluating knee joint laxity using roentgen stereophotogrammetric analysis. Am J Sports Med 39:2536-48
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