title: Echinomycin did not affect the safety of fracture healing: an experimental pilot study on a murine femur fracture model.
abstract: BACKGROUND
  There is a need for effective drugs in the prevention and treatment of heterotopic ossifications (HO) after fractures. Echinomycin has been shown to prevent formation of HO in an animal model. However, before it may be considered as an option against HO, it needs to be studied whether it prevents fracture healing similar to non-steroidal anti-inflammatory drugs (NSAIDS). Therefore, the hypothesis was that echinomycin prevents fracture healing and callus formation.
  
  
  METHODS
  In an experimental murine pilot study, standard blunt femur fractures were induced and retrograde intramedullary compression fixation of the femur was performed. The treatment group (n = 8) received echinomycin (0.3 mg/kg body weight) and the control group (n = 8) did not receive echinomycin. The fractures and implant positions were verified by conventional X-rays immediately postoperatively. As the primary outcome variable, fracture healing (osseous consolidation) was evaluated by conventional X-rays and micro-computed tomography (CT) scans after ten weeks and graded as healed, partial or complete pseudarthrosis. The secondary outcome, callus formation, was graded semi-quantitatively from 0 (mostly absent) to 3 (maximum).
  
  
  RESULTS
  Fracture healing was present in all living cases after ten weeks concerning the treatment group. Partial pseudarthrosis was seen in two cases, one in the treatment and another one in the control group. Complete pseudarthrosis was seen in one case of the control group after an open fracture. Callus formation was similar in both groups with a mean grade of 1.5 within each group. Two cases of the treatment group died.
  
  
  CONCLUSIONS
  As a novel finding, echinomycin did not inhibit fracture healing or callus formation in this in vivo murine standard femur fracture model pilot study. Further studies involving a larger number of cases, quantitative assessment with CT scans and histopathological analysis are needed before generalizing the results of this pilot study.
authors.affiliation: Division of Trauma Surgery, Department of Surgery, University Hospital Zurich, University of Zurich, Ramistrasse 100, 8091 Zurich, Switzerland.
authors.forename: Thorsten
authors.identifier: 0000-0002-6133-3314
authors.initials: T
authors.lastname: Jentzsch
authors.affiliation: Division of Trauma Surgery, Department of Surgery, University Hospital Zurich, University of Zurich, Ramistrasse 100, 8091 Zurich, Switzerland.
authors.forename: Stefan M
authors.initials: SM
authors.lastname: Zimmermann
authors.affiliation: Central Biological Laboratory, University Hospital Zurich, Ramistrasse 100, Zurich, 8091 Switzerland.
authors.forename: Flora
authors.initials: F
authors.lastname: Nicholls
authors.affiliation: Division of Trauma Surgery, Department of Surgery, University Hospital Zurich, University of Zurich, Ramistrasse 100, 8091 Zurich, Switzerland.
authors.forename: Paolo
authors.initials: P
authors.lastname: Cinelli
authors.affiliation: Division of Trauma Surgery, Department of Surgery, University Hospital Zurich, University of Zurich, Ramistrasse 100, 8091 Zurich, Switzerland.
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Simmen
authors.affiliation: Division of Trauma Surgery, Department of Surgery, University Hospital Zurich, University of Zurich, Ramistrasse 100, 8091 Zurich, Switzerland.
authors.forename: Clément M L
authors.initials: CM
authors.lastname: Werner
keywords: Bone healing; Callus formation; Echinomycin; Heterotopic ossification (HO); Murine femur fracture model