Pilon Fractures: An Ideal Model to Understand Biological Factors Implicated in the Pathogenesis of Posttraumatic Osteoarthritis

Category: Ankle Arthritis; Trauma Introduction/Purpose: Intraarticular pilon fractures have a high rate of posttraumatic osteoarthritis (PTOA) despite anatomic reduction of the articular surface. Elevated synovial inflammatory proteins triggered by injury contribute to PTOA development.MicroRNAs (miRNA), regulators of gene expression, are dysregulated in the cartilage of osteoarthritic joints, and their modulation may deter cartilage destruction. Specifically, miRNA-146a is associated with normal cartilage development and prevents overexpression of inflammatory proteins in degenerative osteoarthritis but is yet to be studied in clinical PTOA. This novel study aims to determine the effect of acute intraarticular pilon fracture on miRNA-146a expression and its association with inflammatory proteins. Methods: Bilateral ankles of patients with unilateral pilon fracture were aspirated for synovial fluid at the time of external fixation and/or open reduction internal fixation (ORIF). After processing, synovial fluid samples were sequenced for small RNA analysis. Measured levels of miRNA-146a in injured ankles were compared to the contralateral uninjured ankles, which served as baseline controls. Results: Five patients with unilateral pilon fractures consented to participate in the study. miRNA-146a was readily detectable in all patient samples. Using uninjured ankles (n=5) as a control, mean fold miRNA-146a expression was 1.0 ±0.93 [Mean ± Standard Deviation (SD)]. In comparison, mean fold miRNA-146a in injured ankles (n=5) was 0.4 ± 0.53(p=0.07). Additional results will be analyzed and available to present at the 2024 AOFAS Annual Meeting. Conclusion: Though not statistically significant, our preliminary data demonstrated that miRNA-146a was lower in injured ankles when compared to uninjured ankles. This study aims to better characterize the effect of acute pilon fracture on miRNA-146 expression and its association with inflammatory proteins. Anticipated results will help elucidate the role of miRNA-146a in the pathogenesis of PTOA following pilon fracture, impacting future PTOA research on the diagnostic and therapeutic capabilities of miRNAs.