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A Prospective Randomized Double-Blind Clinical Trial to Assess the Effects of Leukocyte-reduced Platelet-Rich Plasma on Pro-inflammatory, Degradative, and Anabolic Biomarkers after Closed Pilon Fractures


J Orthop Res. 2021 Jun 29. doi: 10.1002/jor.25123. Online ahead of print.

Bradford P Zitsch 1Christopher R James 2Brett D Crist 2Aaron M Stoker 2 3Gregory J Della Rocca 2James L Cook 2 3

Author Information

1 University of Missouri School of Medicine - Columbia, Missouri.

2 University of Missouri Department of Orthopaedic Surgery - Columbia, Missouri.

3 Thompson Laboratory for Regenerative Orthopaedics, University of Missouri - Columbia, Missouri.


Post-traumatic osteoarthritis (PTOA) significantly affects patients with pilon fractures even after adequate anatomical reduction, and treatment strategies targeting the biologic mediators of PTOA are needed. This study was designed to determine the effects of intra-articular injection of platelet-rich plasma (PRP) on synovial fluid (SF) biomarkers for patients undergoing open reduction and internal fixation (ORIF) of pilon fractures. Patients undergoing staged management of pilon fractures were enrolled in a prospective, double-blinded, randomized, placebo-controlled clinical trial to determine the effects of a single intra-articular injection of leukocyte-reduced PRP on SF biomarkers. Arthrocentesis of the injured and uninjured ankles was performed at time of external skeletal fixation (ESF) and ORIF. Patients were randomized to receive either autogenous leukocyte-reduced PRP or saline (control) via intra-articular injection into the injured ankle at time of ESF. SF biomarker concentrations were compared--uninjured, injured pre-treatment, and saline-injected or PRP-injected. Eleven patients (PRP, n=5; saline, n=6) completed the study. 21 un-injured, and 11 injured pre-treatment, 5 PRP-treated, and 6 saline-treated SF samples were analyzed. PRP-treated SF contained significantly higher levels of PDGF-AA (p=0.046) and significantly lower levels of MMP-3 (p=0.042), MMP-9 (p=0.009), IL-1β (p=0.049), IL-6 (p<0.01), IL-8 (p=0.048) and PGE2 (p<0.04). This study provided mechanistic data to suggest that a single intraarticular injection of leukocyte-reduced PRP is associated with anti-inflammatory, anti-degradative and anabolic responses compared to saline control. These findings provide the impetus for investigating long-term clinical outcomes after PRP injection as an orthobiologic adjunct to ORIF for mitigating the incidence and severity of PTOA after pilon fractures. This article is protected by copyright. All rights reserved.