The effect of rhBMP-2 in a novel, non-instrumented extremity nonunion model

J Orthop Sci. 2016 Jan;21(1):79-85. doi: 10.1016/j.jos.2015.10.017. Epub 2015 Nov 28.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Morphogenetic Protein 2 / therapeutic use*
  • Disease Models, Animal
  • Female
  • Fracture Healing / drug effects*
  • Fractures, Ununited / drug therapy*
  • Rats
  • Rats, Sprague-Dawley
  • Recombinant Proteins / therapeutic use
  • Transforming Growth Factor beta / therapeutic use*
  • Ulna Fractures / drug therapy*

Substances

  • Bone Morphogenetic Protein 2
  • Recombinant Proteins
  • Transforming Growth Factor beta
  • recombinant human bone morphogenetic protein-2