Acute Pilon Fracture as a Clinical Model for Posttraumatic Osteoarthritis: A Feasibility Pilot Study of Synovial Fluid miR-146a Expression
5 affiliations
- 1Harvard Medical School Orthopaedic Trauma Initiative, Boston, MA, USA
- 2Department of Orthopaedic Surgery, Massachusetts General Hospital, Boston, MA, USA
- 3Department of Orthopaedic Surgery, University of Kentucky, Lexington, KY, USA
- 4Ortho Virginia and Liberty University, Lynchburg, VA, USA
- 5Department of Orthopaedic Surgery, University of Miami Health System, Miami, FL, USA
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:: Bilateral ankle synovial fluid aspiration was successful in all 5 patients. miR-146a was detectable in all injured and contralateral uninjured ankle samples. Mean miR-146a expression was lower in injured ankles compared with contralateral uninjured controls (0.43 ± 0.59 vs 1.00 ± 1.05; mean paired difference, −0.57 [95%CI, −1.21 to 0.08]; P = .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.
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BibTeX
@article{vise2026acute,
title = {{Acute Pilon Fracture as a Clinical Model for Posttraumatic Osteoarthritis: A Feasibility Pilot Study of Synovial Fluid miR-146a Expression}},
author = {Healy S. Vise and Adam N. Musick and Carla H. Lehle and Jarod T. Griffin and David C. Landy and Arjun Srinath and Arun Aneja},
journal = {Foot \& ankle orthopaedics},
year = {2026},
month = jul,
doi = {10.1177/24730114261481825},
url = {https://europepmc.org/article/PMC/PMC13724950},
note = {CC BY-NC},
}
RIS
TY - JOUR
TI - Acute Pilon Fracture as a Clinical Model for Posttraumatic Osteoarthritis: A Feasibility Pilot Study of Synovial Fluid miR-146a Expression
AU - Healy S. Vise
AU - Adam N. Musick
AU - Carla H. Lehle
AU - Jarod T. Griffin
AU - David C. Landy
AU - Arjun Srinath
AU - Arun Aneja
PY - 2026
DA - 2026/07/01
JO - Foot & ankle orthopaedics
DO - 10.1177/24730114261481825
UR - https://europepmc.org/article/PMC/PMC13724950
AB - 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:: Bilateral ankle synovial fluid aspiration was successful in all 5 patients. miR-146a was detectable in all injured and contralateral uninjured ankle samples. Mean miR-146a expression was lower in injured ankles compared with contralateral uninjured controls (0.43 ± 0.59 vs 1.00 ± 1.05; mean paired difference, −0.57 [95%CI, −1.21 to 0.08]; P = .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.
SN - 2473-0114
ER -