title: The effect of rhBMP-2 in a novel, non-instrumented extremity nonunion model.
abstract: BACKGROUND
  Pre-clinical models of bony nonunion typically employ critical-length defects. However, these models may not accurately reflect clinical practice since many nonunions are diagnosed without bone loss. We developed a non-displaced rat ulna fracture model in order to examine the efficacy of recombinant human bone morphogenetic protein-2 (rhBMP-2) with an absorbable collagen sponge (ACS) for nonunion treatment.
  
  
  METHODS
  Transverse diaphyseal ulna fractures were created in 24 Sprague-Dawley rats. Eight animals (Group 1: Nonunion) received no further intervention. The remaining 16 animals were treated with 5 μg rhBMP-2/ACS at 8 weeks after the original intervention (Group 2: Nonunion + BMP) or at the time of initial injury (Group 3: Fresh fracture + BMP).
  
  
  RESULTS
  In Group 1, 7 of 8 fractures demonstrated gross motion and a persistent radiographic gap (12.5% healing rate). In Groups 2 and 3, fractures healed at a rate of 75% (6 of 8 in each group) as determined by manual and radiographic evaluation. Biomechanical testing for torque load-to-failure and torsional stiffness demonstrated no significant difference between healed specimens treated with rhBMP-2.
  
  
  CONCLUSIONS
  To our knowledge, this is the first description of a physiologic, non-stabilized, non-defect fracture nonunion model in a rodent. Furthermore, unlike previous nonunion models, the healing rates after treatment with rhBMP-2 are comparable to that of clinical data, suggesting that this model may provide an environment more representative of nonunions in humans.
authors.affiliation: Department of Orthopaedic Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
authors.forename: Jason H
authors.initials: JH
authors.lastname: Ghodasra
authors.affiliation: Department of Orthopaedic Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
authors.forename: Brian M
authors.initials: BM
authors.lastname: Weatherford
authors.affiliation: Department of Orthopaedic Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Nickoli
authors.affiliation: Department of Orthopaedic Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
authors.forename: Erika L
authors.initials: EL
authors.lastname: Daley
authors.affiliation: Department of Physical Medicine and Rehabilitation, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
authors.forename: Kai
authors.initials: K
authors.lastname: Chen
authors.affiliation: Department of Physical Medicine and Rehabilitation, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
authors.forename: Li-Qun
authors.initials: LQ
authors.lastname: Zhang
authors.affiliation: Department of Orthopaedic Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
authors.forename: Sohaib Z
authors.initials: SZ
authors.lastname: Hashmi
authors.affiliation: Department of Orthopaedic Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
authors.forename: Erin L
authors.initials: EL
authors.lastname: Hsu
authors.affiliation: Department of Orthopaedic Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA; Department of Neurological Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA. Electronic address: wkhsu@yahoo.com.
authors.forename: Wellington K
authors.initials: WK
authors.lastname: Hsu
mesh_terms: D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000627:therapeutic use*; D004195:Disease Models, Animal; D005260:Female; D017102:Fracture Healing / Q000187:drug effects*; D005599:Fractures, Ununited / Q000188:drug therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000627:therapeutic use; D016212:Transforming Growth Factor beta / Q000627:therapeutic use*; D014458:Ulna Fractures / Q000188:drug therapy*
chemical_list: D055396:Bone Morphogenetic Protein 2; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; C499469:recombinant human bone morphogenetic protein-2