Osteoarthritis, Knee
Conditions
Keywords
Bone Marrow Lesion, BML, Arthroplasty, Replacement, Knee, Discarded tissue
Brief summary
The purpose of the study is to investigate protein and gene expression among damaged knee tissues. We will perform MRI's on subjects prior to total knee replacement to identify the location of bone marrow lesions. 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.
Detailed description
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. 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. 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 to create more specific targets and improve our understanding of the pathology in BMLs. Specific Aim 1: \- To collect tissue to evaluate protein and gene expression of these tissues and cultured cells.
Interventions
RADIATIONMRI
1.5T MRI exam of signal knee with knee coil (estimated time: 35 minutes)
PROCEDUREPrimary Total Knee Replacement
Fluid, bone, and meniscus specimens obtained from total joint replacement will be collected.
Sponsors
The New England Baptist Hospital
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* subjects having primary knee replacement surgery with 1 participating surgeon at NEBH (principal investigator)
Exclusion criteria
* subjects having a revision knee replacement instead of a primary knee replacement * contraindications for MRI * pregnancy
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of Participants With Viable Specimens for Genetic Analysis | Tissue samples collected at time of surgery |
Countries
Australia
Participant flow
Recruitment details
Participants were recruited from 4 orthopedic surgeons at one hospital between the dates of March, 2009 and April, 2013.
Participants by arm
| Arm | Count |
|---|---|
| Enrolled Subjects having primary knee replacement surgery
Exclusion Criteria:
* having a revision knee replacement instead of a primary knee replacement
* contraindicated for MRI or CT scans
* allergy to the contrast agent gadolinium
* pregnant women | 101 |
| Total | 101 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Protocol Violation | 2 |
| Overall Study | radiology error | 2 |
| Overall Study | specimen missed due to scheduling error | 14 |
| Overall Study | specimen unusable | 7 |
| Overall Study | unable/unwilling to complete MRI | 13 |
| Overall Study | Withdrawal by Subject | 3 |
Baseline characteristics
| Characteristic | Enrolled |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 46 Participants |
| Age, Categorical Between 18 and 65 years | 55 Participants |
| Age, Continuous | 63.89 years STANDARD_DEVIATION 8.59 |
| Region of Enrollment United States | 101 participants |
| Sex: Female, Male Female | 50 Participants |
| Sex: Female, Male Male | 51 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 60 |
| serious Total, serious adverse events | 0 / 60 |
Outcome results
Primary
Number of Participants With Viable Specimens for Genetic Analysis
Time frame: Tissue samples collected at time of surgery
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Specimens | Number of Participants With Viable Specimens for Genetic Analysis | 14 participants |