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The purpose of the study is to investigate the density, architecture, and perfusion of bone marrow lesions (BMLs) in knee osteoarthritis. We will perform MRI's and QCT's on subjects prior to total knee replacement to identify the location of BMLs. Connective tissues including tendon, ligament, and meniscus specimens normally discarded from total joint replacements will be used for live cell harvest, and protein and gene expression analyses of tissue or cultured cells.
BACKGROUND AND SIGNIFICANCE:
Although the presence of bone marrow lesions (BML) on MRI is strongly associated with osteoarthritis (OA) progression and pain in some studies, the mechanism for this relation and the underlying pathology is not well established. The lack of knowledge on what these lesions constitute hampers their clinical utility both with regards to measurement and targeting for therapeutic intervention. In addition, prior studies in the hip have suggested that OA is associated with increased intraosseous pressures, which was thought to be the result of obstruction of venous drainage from the affected bone. It has been suggested that elevated intraosseous pressure is responsible for the pain, bone-remodeling as well as the necrosis of bone occurring in patients who have these diseases.
Our preliminary data has localized specific changes in bone mineralization, remodeling and defects within BML features that are adjacent to the subchondral plate. BMLs appear to be sclerotic compared to unaffected regions; however, the mineral density in these lesions is reduced and may render this area to be mechanically compromised, and thus susceptible to attrition. Areas of bone affected by BML in knee OA appear to be associated with altered perfusion and intraosseous venous hypertension in both the tibial plateau and femur while increased permeability was observed in the tibial plateau only. These alterations in bone perfusion and hypertension may be responsible for rest pain as well as the bone-remodeling and the necrosis of bone occurring in patients with knee OA. Limited histological analysis of BMLs reveal thrombi, diffuse fibrinoid necrosis and hyperplasia of blood vessel walls - all indicative of infarction-like pathology.
The aim of this research proposal is confirm our preliminary data obtained by pilot studies in a larger sample set and extend these findings to create more specific targets and improve our understanding of the pathology in BMLs and their relation to pain.
Specific Aim 1:
- To examine the relation of BML perfusion to rest and night pain.
Specific Aim 2:
- To evaluate the relation of BML size to BML perfusion and pain severity.
Specific Aim 3:
- To evaluate the relation between BML size and perfusion, bone density, and histomorphometry.
Specific Aim 4:
- To collect tissue to evaluate protein and gene expression of these tissues and cultured cells.
Observational Model: Case Control, Time Perspective: Prospective
MRI with gadolinium infusion, Computer Tomography (CT), Total Knee Replacement
New England Baptist Hospital
Active, not recruiting
The New England Baptist Hospital
Published on BioPortfolio: 2014-07-24T14:14:13-0400
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