The Relationship Between Intra-Articular Fracture Energy and a Patient's Inflammatory Response.

Abstract

Prior studies have demonstrated elevated inflammatory cytokine concentrations in the synovial fluid of articular fracture patients post-injury. Similarly, CT-based fracture energy measurements have been correlated to PTOA risk after pilon fracture. The purpose of this study was to determine the associations between synovial fluid cytokine levels, fracture energy, and overall trauma to the body in articular fracture patients. Acute tibial plateau, tibial plafond, and rotational ankle fracture patients were prospectively enrolled from December 2011 through January 1, 2019. Synovial fluid concentrations of IL-1β, IL-1RA, IL-6, IL-8, IL-10, MMP-1, MMP-3, and MMP-13 were quantified. Patient CT scans were used to calculate fracture energy. The Injury Severity Score (ISS) was used to relate cytokine levels to whole-body injury severity. Spearman's rho correlation coefficients were calculated to assess the relationship between injury severity metrics and synovial fluid cytokine, chemokine, and MMP concentrations. Eighty-seven patients were enrolled with 42 had a tibial plateau fractures (OTA/AO 41B1 - 2, 41B2-14, 41B3-3, 41C1-3, 41C2-4, 41C3-16), 24 patients had a tibial plafond fracture (OTA/AO 43B1 - 2, 43B2 - 4, 43B3 - 5, 43C1 - 2, 43C2-3, 43C3-8), and 21 had a rotational ankle fracture (OTA/AO 44B1-3, 44B2-3, 44B3-6, 44C1-4, 44C2-5). Fracture energy significantly differed between fracture patterns, with ankle fractures involving substantially less fracture energy (median = 2.92 J) than plafond (10.85 J, p<0.001) and plateau fractures (13.05 J, p<0.001). After adjustment for multiple comparisons, MMP-3 was significantly correlated with transformed fracture energy (r=0.41, 95% CI 0.22-0.58, p<0.001), while IL-1β was significantly correlated with ISS, (Spearman's ρ=0.31, 95% CI 0.08 - 0.49, p=0.004). Synovial fluid MMP-3 concentration was significantly correlated with CT-quantified fracture energy in intra-articular fracture patients. Given that in clinical practice fracture energy tends to correlate with post-traumatic osteoarthritis (PTOA) risk, MMP-3 may warrant further investigation for its role in PTOA development after articular fracture.