Principal Investigator: Justin Haller
Keywords: Arthritis , Imaging , PedCAT Department: Orthopedic Surgery Operations
IRB Number: 00139629
Specialty: Orthopaedic Surgery
Sub Specialties: Orthopaedic Trauma
Recruitment Status: Enrolling by invitation

Contact Information

Zach Olsen

Brief Summary

Surgeons treat high-energy intra-articular fractures (IAFs) by reducing and stabilizing the joint, but disabling post-traumatic osteoarthritis (PTOA) nonetheless all-too-often ensues. Recent research indicates that IAFs initiate a sequence of biologic events triggering joint degeneration. Strong evidence is emerging that new biologic agents could mitigate or arrest these events.

These findings offer hope for a paradigm shift in treating IAFs, but controlled clinical trials are needed. Two major barriers remain: (1) it takes years to determine if new treatments work because PTOA develops relatively slowly and early changes are difficult to detect and (2) it is difficult to predict PTOA risk, making it virtually impossible to do controlled clinical trials.

As for detecting PTOA early, IAF patients are followed with radiographs, which are insensitive to detecting OA until later stages. A new upright standing CT (PedCT scanner) has promise to detect OA earlier, because of its 3D nature and ability to image in a weight-bearing pose. This advance comes at the cost similar to plain radiographs and an equivalent relative radiation level. 

The small footprint of the scanner and lack of ongoing fixed costs permits even small community clinics to offer SCT. SCT-enabled imaging biomarkers could advance clinical care and hasten the pace of discovery. Regarding PTOA risk prediction, we have developed CT-based methods to quantify IAF severity and elevated contact stress from residual incongruity, influential mechanical risk factors. In a prospective study of tibial pilon fractures, patients stratified using these metrics showed thresholds above which PTOA was nearly inevitable. This presents an objective means to risk-stratify patients for controlled clinical study. The objective of the proposed research is to establish a more sensitive SCT-enabled imaging biomarker for PTOA. Coupling this biomarker with methods for assessing mechanical risk factors using images from the SCT will enable better prediction, earlier diagnosis, and more meaningful longitudinal assessment of PTOA. This will lead to better-informed treatment decisions and provide a framework for the clinical testing of new biologic treatments to prevent or forestall PTOA.

Our long-term objective is to accelerate approval of better treatment options for patients, while reducing the burden of trial duration and costs for PTOA studies. The specific aim is to establish affordable imaging biomarkers that detect PTOA earlier. Patients with an intra-articular fracture at high risk for developing PTOA will be studied at three sites. 

Aim 1: Determine the impact of post-operative ankle reduction on patient-centered outcome scores. Hypothesis: Articular malreduction in plafond fracture is associated with worse PROMIS-29 score at 12 months post-injury. Tibial plafond malreduction (step-off and gap) will be quantified on coronal and sagittal weight-bearing imaging sequences at the post-operative time point. Maximum step-off and gap measurements will then be compared with PROMIS-29 scores. Secondary aims will be to examine the relationship between PROMIS-29 scores with mechanical alignment and anatomic plafond components. 

Aim 2: Determine the relationship between subchondral cyst formation and PROMIS-29 scores in tibial plafond fractures.  Hypothesis: 6-month subchondral cyst formation in plafond fractures is associated with PROMIS-29 score at 12 months post-injury. As a secondary analysis, we will describe and compare cyst formation and PROMIS-29 at each of the following four time points: post-op, pre-weight bearing, 6 months, and 12 months to describe subchondral cyst progression and the PROMIS-29 recovery trajectory.   

Aim 3: Identify post-injury inflammatory cytokine synovial biomarkers that correspond with worse PROMIS-29 scores.  Hypothesis: Acute IL-1b concentration in synovial fluid is associated with worse PROMIS-29 score at 12 months post-injury

. Synovial fluid will be aspirated from tibial plafond fracture patients within 24 hours of injury. Inflammatory cytokines (IL-1b, IL-6, IL-8, IL-10, MMP-1, and MMP-13) will be quantified using a multiplex assay. Associations between initial cytokine concentration and PROMIS-29 at 12 months will be analyzed. Secondary aims will be to compare fracture severity with inflammatory cytokine concentration and compare 12-month WBCT scan with initial cytokine concentration

Detailed Description

Patients will be identified either in clinic or in the emergency department and will be approached about the study. Eligibility will be determined by the principal investigator, and consent will be obtained. The patient will undergo corrective, open reduction internal fixation for their tibial plafond break. The operation will be considered standard of care. During the operation, a synovial fluid aspiration will be performed. The fluid that's collected will be stored in a -80 C freezer until a batch analysis can be performed, likely once all patients have been enrolled. The patients will then receive a PedCT x-ray ~3 weeks from their injury and at their 3-month post-operative clinic visit, and again at 6 months, and again at 12 months, and 18 months.The pedCT scans will be de-identified and shared with the University of Iowa via encrypted software, no patient identifiers will be shared. After each scan patients will be asked to fill out the: PROMIS Bank v2.0 - Physical Function, PROMIS Bank v1.1 - Pain Interference, PROMIS Bank v1.0 - Anxiety, PROMIS Bank v1.0 Depression, (FAAM) Foot and Ankle Measure, and a question asking: On a scale from 0 to 100, with 0 representing "zero likelihood of returning to previous level of function" and 100 representing "100% likelihood of returning to previous level of function," how likely do you believe you are of returning to your previous level of function at some point after your fracture/trauma? The questionnaires will take approximately 30 minutes to complete.If the patient is unable to fill out the questionnaires at their visit, or if they were missed for whatever reason, study personnel will attempt to contact them via phone, email, or mail specific to contact information on file.The participant's email address will be confirmed at their clinic visit by study personnel. Those with a working email address will have the option to complete the questionnaires online. Study personnel will email them a hyperlink. The hyperlink will lead them to a secure internet website portal for data collection called REDCAP, where they can complete the questionnaires electronically.If they do not have an email address and cannot complete the paper questionnaires at their clinic visit, study personnel will send the participant home with a stamped self-addressed envelope to facilitate returning the questionnaires upon completion. If study personnel does not receive the questionnaires back after a couple of weeks, study personnel may contact them by phone to follow up. The questionnaires can also be completed over the phone. After arranging a time that works for them, study personnel will collect participant questionnaire answers over the phone should that work best for them.

Inclusion Criteria

Subjects will be individuals who sustain an IAF of the tibial plafond and present to the UUOC Department of Orthopaedics or the UofU Emergency Department for operative treatment within four weeks of injury. 

Exclusion Criteria

Women who are pregnant or planning on becoming pregnant will be excluded.