title: Prevention of heterotopic ossification: an experimental study using a plasma expander in a murine model.
abstract: BACKGROUND
  Heterotopic ossification (HO) is a frequent complication following orthopedic and trauma surgery. It often leads to substantial morbidity as many affected patients suffer from pain and joint contractures. Current prophylactic measures include nonsteroidal anti-inflammatory drugs (NSAID) and local radiation. However, several disadvantages such as delayed fracture healing and impaired ossification have been reported. For this reason, a novel approach for prevention of HO was searched for. We hypothesized that systemic administration of hydroxyethyl starch (HES), a substance known to influence microcirculation, would reduce formation of HO in a murine model.
  
  
  METHODS
  A pre-established murine model was used where HO has been shown to develop following Achilles tendon tenotomy. Twenty CD1 mice were randomly assigned to a control (n = 10) or treatment group (n = 10). The treatment group received two intravenous HES injections perioperatively, while the control group underwent tenotomy only. After ten weeks, the mice were euthanized and micro CT scans of the hind limbs were performed. HO was manually identified and quantitatively assessed. A Wilcoxon rank sum test was used for comparison of both groups.
  
  
  RESULTS
  The mean heterotopic bone volume in the control group was significantly larger compared to the HES group (2.276 mm(3) vs. 0.271 mm(3), p = 0.005). A reduction of mean ectopic bone volume of 88 % was found following administration of HES.
  
  
  CONCLUSIONS
  A substantial reduction of HO formation was found following perioperative short-term administration of HES. This work represents a preliminary study, necessitating further studies before drawing ultimate conclusions. However, this simple addition to current prophylactic measures might lead to a more effective prevention of HO in the future.
authors.affiliation: Department of Surgery, Division of Trauma Surgery, University Hospital Zurich, Raemistrasse 100, 8091, Zürich, Switzerland. st.zimmermann@gmx.ch.
authors.forename: Stefan M
authors.initials: SM
authors.lastname: Zimmermann
authors.affiliation: Department of Surgery, Division of Trauma Surgery, University Hospital Zurich, Raemistrasse 100, 8091, Zürich, Switzerland.
authors.forename: Lukas W
authors.initials: LW
authors.lastname: Schwitter
authors.affiliation: Department of Surgery, Division of Trauma Surgery, University Hospital Zurich, Raemistrasse 100, 8091, Zürich, Switzerland.
authors.forename: Max J
authors.initials: MJ
authors.lastname: Scheyerer
authors.affiliation: Department of Surgery, Division of Trauma Surgery, University Hospital Zurich, Raemistrasse 100, 8091, Zürich, Switzerland.
authors.forename: Thorsten
authors.initials: T
authors.lastname: Jentzsch
authors.affiliation: Department of Surgery, Division of Trauma Surgery, University Hospital Zurich, Raemistrasse 100, 8091, Zürich, Switzerland.
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Simmen
authors.affiliation: Department of Surgery, Division of Trauma Surgery, University Hospital Zurich, Raemistrasse 100, 8091, Zürich, Switzerland.
authors.forename: Clément M L
authors.initials: CM
authors.lastname: Werner
mesh_terms: D000125:Achilles Tendon / Q000601:surgery*; D000818:Animals; D004195:Disease Models, Animal; D006895:Hydroxyethyl Starch Derivatives / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D009999:Ossification, Heterotopic / Q000209:etiology / Q000517:prevention & control*; D010952:Plasma Substitutes / Q000627:therapeutic use*; D011897:Random Allocation; D058971:Tenotomy / Q000009:adverse effects*; D014057:Tomography, X-Ray Computed
chemical_list: C485123:HES 130-0.4; D006895:Hydroxyethyl Starch Derivatives; D010952:Plasma Substitutes
keywords: Bone; Heterotopic; Hydroxyethyl starch; Model; Murine; Ossification; Voluven