Improved healing efficacy in canine ulnar segmental defects with increasing recombinant human bone morphogenetic protein-2/allograft ratios

J Orthop Trauma. 2008 Sep;22(8):550-9. doi: 10.1097/BOT.0b013e318180f0f0.

Abstract

Objectives: A validated canine critical-sized segmental defect model was used to compare efficacy of volumetric ratios of recombinant human bone morphogenetic protein-2 (rhBMP-2)/absorbable collagen sponge (ACS) with cancellous allograft bone or biphasic calcium phosphate ceramic granules using radiographic, biomechanical, and histologic analyses.

Methods: Eighteen mixed-breed hounds received bilateral critical-sized ulnar segmental defects. The six treatment groups included 1:5, 1:2, and 1:1 volumetric ratios of rhBMP-2/ACS to cancellous allograft chips; a 1:1 volumetric ratio of rhBMP-2/ACS to biphasic calcium phosphate ceramic granules; iliac crest autograft alone; and cancellous allograft chips alone (n = 6 ulna per group). Animals were euthanized at 12 weeks and analyzed by radiography, torsion testing, and histology.

Results: rhBMP-2/ACS groups demonstrated higher radiographic union than autograft or allograft at 12 weeks. Both treatment groups receiving a 1:1 ratio demonstrated union rates of 100% (12/12 ulna) compared with 17% (1/6) and 0% (0/6) for autograft and allograft, respectively. Torsion testing to failure demonstrated significant increases in maximum torque for all rhBMP-2 groups compared with autograft, but no differences between the rhBMP-2 groups. Ulnae treated with the 1:1 volume ratio of rhBMP-2/ACS to ceramic had the highest histologic union grades followed by 1:1 and 1:2 volume ratios of rhBMP-2/ACS to allograft.

Conclusions: In this study, efficacy of the treatment correlated with the ratio of rhBMP-2/ACS to allograft. As volume of rhBMP-2/ACS decreased below a 1:1 volume ratio, the overall efficacy decreased, thus indicating a potential limit to extending rhBMP-2/ACS past a 1:1 volumetric ratio in large segmental defects. Furthermore, ceramic was found to be a successful replacement for cancellous allograft bone at a 1:1 volumetric ratio. Clinical application using graft expanders or bone void fillers with rhBMP-2 should be used carefully and requires further investigation.

MeSH terms

  • Animals
  • Biomechanical Phenomena
  • Bone Morphogenetic Protein 2
  • Bone Morphogenetic Proteins / therapeutic use*
  • Bone Remodeling / drug effects
  • Bone Remodeling / physiology
  • Bone Transplantation*
  • Ceramics / pharmacology
  • Coated Materials, Biocompatible
  • Disease Models, Animal
  • Dogs
  • Female
  • Fracture Healing / drug effects*
  • Fracture Healing / physiology
  • Hydroxyapatites / pharmacology
  • Male
  • Osseointegration / drug effects
  • Recombinant Proteins / therapeutic use*
  • Transforming Growth Factor beta / therapeutic use*
  • Ulna / drug effects
  • Ulna / pathology
  • Ulna / surgery*
  • Ulna Fractures / drug therapy
  • Ulna Fractures / pathology
  • Ulna Fractures / surgery*

Substances

  • Bone Morphogenetic Protein 2
  • Bone Morphogenetic Proteins
  • Coated Materials, Biocompatible
  • Hydroxyapatites
  • Recombinant Proteins
  • Transforming Growth Factor beta
  • hydroxyapatite-beta tricalcium phosphate
  • recombinant human bone morphogenetic protein-2