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Acute Pilon Fracture as a Clinical Model for Posttraumatic Osteoarthritis: A Feasibility Pilot Study of Synovial Fluid miR-146a Expression

Year: 2026

Type: article

Abstract: Background: Posttraumatic osteoarthritis (PTOA) is a frequent and debilitating sequela of intraarticular ankle fractures that progresses more rapidly than primary osteoarthritis. Pilon fractures demonstrate among the highest rates of PTOA and represent an attractive clinical model for studying early biological mechanisms of posttraumatic joint degeneration. Emerging evidence suggests dysregulated inflammation following intraarticular injury contributes to PTOA pathogenesis. miR-146a is a microRNA and a regulator of inflammatory signaling and cartilage homeostasis that has been implicated in osteoarthritis biology; however, its role in human PTOA following pilon fractures remains undefined. Methods: This prospective pilot study enrolled 5 adults (18-60 years) with acute closed unilateral pilon fractures. Bilateral ankle synovial fluid aspiration was performed at the time of definitive fixation. The contralateral uninjured ankle served as an internal control. Synovial fluid samples were obtained a mean of 14 days (range, 11-19) following injury. Four patients underwent staged temporary external fixation prior to definitive fixation, whereas 1 patient was managed with splint immobilization. Samples were processed for small RNA analysis and inflammatory protein quantification. miR-146a expression and concentrations of pro-inflammatory cytokines were compared between injured and uninjured ankles. Results: = .07). Exploratory descriptive analyses demonstrated inverse correlations between miR-146a expression and concentrations of interleukin (IL)-1β, IL-6, IL-8, and tumor necrosis factor α. Conclusion: Synovial fluid aspiration and miR-146a quantification following acute pilon fracture were feasible in all participants. miR-146a was detectable in both injured and contralateral uninjured ankles in all samples. Further study is warranted to characterize synovial miRNA expression and inflammatory signaling following pilon fracture. Level of Evidence: Level IV, prognostic.

Source: Foot & Ankle Orthopaedics

DOI: 10.1177/24730114261481825