title: A 5-mm femoral defect in female but not in male rats leads to a reproducible atrophic non-union.
abstract: BACKGROUND
  The objectives of this study were to (1) establish a reproducible atrophic non-union model in rats by creation of a segmental femoral bone defect that allows, (2) in-depth characterization of impaired healing, and (3) contrast its healing patterns to the normal course. Hypothesis was that a 5-mm bone defect in male rats would deviate from uneventful healing patterns and result in an atrophic non-union.
  
  
  METHODS
  A femoral osteotomy was performed in two groups of 12-week-old male rats (1 vs. 5 mm gap) stabilized with an external fixator. Bone healing in these models was evaluated by radiology, biomechanics, and histology at 6 or 8 weeks. The evaluation of the 5-mm group revealed in some cases a delayed rather than a non-union, and therefore, a group of female counterparts was included.
  
  
  RESULTS
  The creation of a 5-mm defect in female rats resulted in a reproducible atrophic non-union characterized by sealing of the medullary canal, lack of cartilage formation, and negligible mechanical properties of the callus. In both gap size models, the male subjects showed advanced healing compared to females.
  
  
  CONCLUSIONS
  This study showed that even under uneventful healing conditions in terms of age and bone defect size, there is a sex-specific advanced healing in male compared to female subjects. Contrary to our initial hypothesis, only the creation of a 5-mm segmental femoral defect in female rats led to a reproducible atrophic non-union. It has been shown that an atrophic non-union exhibits different healing patterns compared to uneventful healing. A total lack of endochondral bone formation, soft tissue prolapse into the defect, and bony closure of the medullary cavity have been shown to occur in the non-union model.
authors.affiliation: Julius Wolff Institute and Center for Musculoskeletal Surgery, Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany.
authors.forename: Manav
authors.initials: M
authors.lastname: Mehta
authors.forename: Hanna
authors.initials: H
authors.lastname: Schell
authors.forename: Carolin
authors.initials: C
authors.lastname: Schwarz
authors.forename: Anja
authors.initials: A
authors.lastname: Peters
authors.forename: Katharina
authors.initials: K
authors.lastname: Schmidt-Bleek
authors.forename: Agnes
authors.initials: A
authors.lastname: Ellinghaus
authors.forename: Hermann J
authors.initials: HJ
authors.lastname: Bail
authors.forename: Georg N
authors.initials: GN
authors.lastname: Duda
authors.forename: Jasmin
authors.initials: J
authors.lastname: Lienau
mesh_terms: D000818:Animals; D001284:Atrophy; D002146:Bony Callus / Q000473:pathology; D004195:Disease Models, Animal; D016267:External Fixators; D005260:Female; D005264:Femoral Fractures / Q000601:surgery*; D007091:Image Processing, Computer-Assisted; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012737:Sex Factors; D014945:Wound Healing