Characterizing the host response to rhBMP-2 in a rat spinal arthrodesis model

Spine (Phila Pa 1976). 2013 May 20;38(12):E691-8. doi: 10.1097/BRS.0b013e31828cb977.


Study design: Prospective, randomized, controlled preclinical trial.

Objective: This study seeks to characterize the localized and systemic host response to recombinant human bone morphogenetic protein-2 (rhBMP-2) in a well established rodent spine arthrodesis model utilizing cytokine analysis and magnetic resonance imaging (MRI).

Summary of background data: Although high fusion rates are achieved with rhBMP-2 in the spine, several complications have also been reported, including a localized response leading to radiculitis and seroma formation. The mechanism in which this occurs clinically is yet unknown.

Methods: One hundred female Fischer rats underwent a posterolateral intertransverse lumbar spinal fusion, with paraspinal muscle tissue resection, using iliac crest autograft, type I absorbable collagen sponge (ACS), 10- or 100-μg rhBMP-2/ACS. The animals underwent magnetic resonance imaging evaluation, serum cytokine analysis, manual palpation, and gross tissue inspection at 2, 4, 7, 10, and 21 days, postoperatively.

Results: Qualitative evaluation of MR images demonstrated a transient fluid collection at the surgery site in the rhBMP-2 animals as early as 4 and 7 days that was greater than the autograft or ACS groups. Quantitative analysis on T2-weighted axial images demonstrated greater signal intensity in the rhBMP-2 animals compared with the ACS and autograft groups in a time-dependent fashion. Higher concentrations of several cytokines were also detected at 2, 4, and 7 days, including interleukin 1β, interleukin 18, tumor necrosis factor α, macrophage inflammatory protein 1α, and monocyte chemotactic protein 1 in animals treated with rhBMP-2/ACS relative to ACS alone.

Conclusion: Our data suggest that the in vivo host response to rhBMP-2 in an animal model may be associated with circulating proinflammatory and osteoclastic cytokines.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autografts
  • Bone Morphogenetic Protein 2 / administration & dosage
  • Bone Morphogenetic Protein 2 / toxicity*
  • Bone Transplantation
  • Cytokines / blood
  • Female
  • Humans
  • Ilium / transplantation
  • Inflammation Mediators / blood
  • Lumbar Vertebrae / drug effects*
  • Lumbar Vertebrae / metabolism
  • Lumbar Vertebrae / pathology
  • Lumbar Vertebrae / surgery*
  • Magnetic Resonance Imaging
  • Models, Animal
  • Osteolysis / blood
  • Osteolysis / chemically induced*
  • Rats, Inbred F344
  • Recombinant Proteins / toxicity
  • Seroma / blood
  • Seroma / chemically induced*
  • Seroma / pathology
  • Spinal Fusion* / adverse effects
  • Surgical Sponges
  • Time Factors


  • BMP2 protein, human
  • Bone Morphogenetic Protein 2
  • Cytokines
  • Inflammation Mediators
  • Recombinant Proteins