UVM Theses and Dissertations
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Print
Author:
Tourville, Timothy Ward
Dept./Program:
Center for Clinical and Translational Science
Year:
2011
Degree:
Ph. D.
Abstract:
BACKGROUND: Osteoarthritis (OA) is the most prevalent joint disease and leading cause of disability worldwide, and is a substantial source of pain, dysfunction, and economic burden for millions of individuals. Previous joint injury is a substantial risk factor for the development of early-onset OA, resulting in secondary, or post-traumatic OA (PTOA). Injury to the Anterior Cruciate Ligament (ACL) leads to PTOA in a large subset of individuals, regardless of treatment intervention (surgical or non-surgical). However, little is known regarding the initial changes occurring within the joint during the onset and progression of the disease. At the present time it is not clear how to best assess the earliest stages of PTOA radiographically (when patients are asymptomatic) or what underlying physiological processes may be driving the disease process during its infancy. Consequently, the purpose of this series of scientific investigations was to evaluate tibiofemoral joint space width (JSW) following ACL injury and subsequent surgical reconstruction (ACL-R) and examine select biochemical markers of type-II collagen metabolism that may provide a mechanistic rationale for the observed changes in JSW compared to matched control subjects. We also evaluated the extent to which meniscal and articular cartilage injures noted at the time of ACL reconstruction act as potential prognostic risk factors for PTOA in a cohort of acute, first-time ACL-injured subjects with no history of prior joint injury.
STUDY DESIGN: Prospective cohort with nested case-control analysis.
METHODS: Thirty-eight ACL-injured and 32 matched control subjects were evaluated. Subjects were assessed at baseline (presurgery) and at 3-4 year post-surgical follow-up. Bilateral knee radiographs were obtained at each visit and JSWs calculated. Serum and urinary biochemical markers of type-II collagen metabolism were evaluated via ELISA. Concomitant injuries to the menisci and articular cartilage (sustained during the index ACL injury) were evaluated at the time of surgical ACL reconstruction, risk groups formed based on degree of injuries, and JSW comparisons made at final follow-up based on risk group.
RESULTS: Control knee JSW's were not significantly different bilaterally, and "healthy" knee JSW's (controls and non-injured ACL-R subject knees) did not change significantly over time. ACL-R knee JSW's were significantly different than controls at baseline (increased and decreased JSW values). This suggests that the injury results in "abnormal" JSW values for some individuals soon after injury. At follow-up, 2 ACL-R subjects had decreased JSW scores in the medial compartment, and 3 had increased JSW scores. Lateral compartment analyses revealed 7 subjects with significantly decreased JSW scores at follow-up, but no subjects increased. uCTX-II to sCPII ratio was significantly different in ACL-R subjects with abnormal JSW at follow-up compared to controls. In addition, ACL-R subjects who sustained Grade 3 articular cartilage lesions or any meniscectomy were significantly more likely to have abnormal JSW at follow-up than subjects without these injuries.
DISCUSSION: These results provide the scientific rationale for use of a subjects' non-injured knee as a reference/control knee, elucidates potential biomarkers that have the ability to discriminate between normal (healthy) subjects and ACL-R subjects with abnormal JSW values, and highlights the importance of meniscal and articular cartilage injuries sustained during the index injury on the development of PTOA in what may be some of the earliest observable stages of the disease process.
STUDY DESIGN: Prospective cohort with nested case-control analysis.
METHODS: Thirty-eight ACL-injured and 32 matched control subjects were evaluated. Subjects were assessed at baseline (presurgery) and at 3-4 year post-surgical follow-up. Bilateral knee radiographs were obtained at each visit and JSWs calculated. Serum and urinary biochemical markers of type-II collagen metabolism were evaluated via ELISA. Concomitant injuries to the menisci and articular cartilage (sustained during the index ACL injury) were evaluated at the time of surgical ACL reconstruction, risk groups formed based on degree of injuries, and JSW comparisons made at final follow-up based on risk group.
RESULTS: Control knee JSW's were not significantly different bilaterally, and "healthy" knee JSW's (controls and non-injured ACL-R subject knees) did not change significantly over time. ACL-R knee JSW's were significantly different than controls at baseline (increased and decreased JSW values). This suggests that the injury results in "abnormal" JSW values for some individuals soon after injury. At follow-up, 2 ACL-R subjects had decreased JSW scores in the medial compartment, and 3 had increased JSW scores. Lateral compartment analyses revealed 7 subjects with significantly decreased JSW scores at follow-up, but no subjects increased. uCTX-II to sCPII ratio was significantly different in ACL-R subjects with abnormal JSW at follow-up compared to controls. In addition, ACL-R subjects who sustained Grade 3 articular cartilage lesions or any meniscectomy were significantly more likely to have abnormal JSW at follow-up than subjects without these injuries.
DISCUSSION: These results provide the scientific rationale for use of a subjects' non-injured knee as a reference/control knee, elucidates potential biomarkers that have the ability to discriminate between normal (healthy) subjects and ACL-R subjects with abnormal JSW values, and highlights the importance of meniscal and articular cartilage injuries sustained during the index injury on the development of PTOA in what may be some of the earliest observable stages of the disease process.