title: Inflammatory Microenvironment Persists After Bone Healing in Intra-articular Ankle Fractures.
abstract: BACKGROUND
  Post-traumatic osteoarthritis (PTOA) is responsible for the majority of cases of ankle arthritis. While acute and end-stage intra-articular inflammation has previously been described, the state of the joint between fracture healing and end-stage PTOA remains undefined. This study characterized synovial fluid (SF) composition of ankles after bone healing of an intra-articular fracture to identify factors that may contribute to the development of PTOA.
  
  
  METHODS
  Of an original 21 patients whose SF was characterized acutely following intra-articular ankle fractures, 7 returned for planned hardware (syndesmotic screw) removal after bone healing (approximately 6 months) and consented to a second bilateral SF collection. SF concentrations of 15 cytokines and matrix metalloproteinases (MMPs) and 2 markers each of cartilage catabolism (CTXII and glycosaminoglycan) and hemarthrosis (biliverdin and bilirubin) were compared for previously fractured and contralateral, uninjured ankles from the same patient. Analysis was also performed to determine the effect of the number of fracture lines and involvement of soft tissue on SF composition.
  
  
  RESULTS
  Interleukin (IL)-6, IL-8, MMP-1, MMP-2, and MMP-3 were significantly elevated in the SF from healed ankles compared to matched contralateral uninjured ankles at approximately 6 months after fracture. There were no differences in markers of cartilage catabolism or hemarthrosis. Only IL-1α was affected by the number of fracture lines while differences were not detected for other analytes or with respect to the involvment of soft tissue.
  
  
  CONCLUSIONS
  Sustained intra-articular inflammation, even after complete bone healing, was suggested by elevations of pro-inflammatory cytokines (IL-6 and IL-8). In addition, elevated concentrations of MMPs were also noted and were consistent with a persistent inflammatory environment. This study suggests new evidence of persistent intra-articular inflammation after intra-articular ankle fracture healing and suggests potential mediators for PTOA development.
  
  
  CONCLUSIONS
  This work may be relevant to the clinical diagnosis and treatment of post-traumatic osteoarthritis.
authors.affiliation: 1 Department of Orthopaedic Surgery, Duke University Medical Center, Durham, NC, USA.
authors.forename: Samuel B
authors.initials: SB
authors.lastname: Adams
authors.affiliation: 2 Department of Biomedical Engineering, Washington University in St Louis, St Louis, MO, USA.|3 Albany Medical College, Albany, NY, USA.|4 Department of Biomedical Engineering, Duke University, Durham, NC, USA.
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Leimer
authors.affiliation: 2 Department of Biomedical Engineering, Washington University in St Louis, St Louis, MO, USA.
authors.forename: Lori A
authors.initials: LA
authors.lastname: Setton
authors.affiliation: 5 Department of Pathology, Rochester, University of Rochester Medical Center, NY, USA.
authors.forename: Richard D
authors.initials: RD
authors.lastname: Bell
authors.affiliation: 1 Department of Orthopaedic Surgery, Duke University Medical Center, Durham, NC, USA.
authors.forename: Mark E
authors.initials: ME
authors.lastname: Easley
authors.affiliation: 7 Duke Molecular Physiology Institute, Durham, NC, USA.
authors.forename: Janet L
authors.initials: JL
authors.lastname: Huebner
authors.affiliation: 7 Duke Molecular Physiology Institute, Durham, NC, USA.
authors.forename: Thomas V
authors.initials: TV
authors.lastname: Stabler
authors.affiliation: 1 Department of Orthopaedic Surgery, Duke University Medical Center, Durham, NC, USA.|6 Division of Rheumatology and Immunology, Department of Pathology, Duke University Department of Medicine, Durham, NC, USA.|7 Duke Molecular Physiology Institute, Durham, NC, USA.
authors.forename: Virginia B
authors.initials: VB
authors.lastname: Kraus
authors.affiliation: 1 Department of Orthopaedic Surgery, Duke University Medical Center, Durham, NC, USA.
authors.forename: Steven A
authors.initials: SA
authors.lastname: Olson
authors.affiliation: 1 Department of Orthopaedic Surgery, Duke University Medical Center, Durham, NC, USA.
authors.forename: Dana L
authors.initials: DL
authors.lastname: Nettles
mesh_terms: D064386:Ankle Fractures / Q000503:physiopathology / Q000601:surgery*; D015415:Biomarkers; D016207:Cytokines / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism* / Q000502:physiology; D015850:Interleukin-6 / Q000737:chemistry / Q000378:metabolism*; D057072:Intra-Articular Fractures / Q000601:surgery*; D020782:Matrix Metalloproteinases / Q000737:chemistry / Q000378:metabolism*; D010003:Osteoarthritis / Q000378:metabolism / Q000503:physiopathology*; D013582:Synovial Fluid / Q000737:chemistry / Q000378:metabolism
chemical_list: D015415:Biomarkers; D016207:Cytokines; D018836:Inflammation Mediators; D015850:Interleukin-6; D020782:Matrix Metalloproteinases
keywords: ankle fracture; inflammatory; intra-articular; osteoarthritis; post-traumatic; synovial fluid