title: Characterizing the host response to rhBMP-2 in a rat spinal arthrodesis model.
abstract: METHODS
  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).
  
  
  BACKGROUND
  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.
  
  
  CONCLUSIONS
  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.
authors: *Department of Orthopaedic Surgery †Departments of Radiology and Biomedical Engineering, Northwestern University Feinberg School of Medicine, Chicago, IL; and ‡Department of Research and Development, Medtronic Sofamor Danek, Inc, Memphis, TN.
authors: Wellington K
authors: WK
authors: Hsu
authors: Mahesh
authors: M
authors: Polavarapu
authors: Rehan
authors: R
authors: Riaz
authors: Andrew C
authors: AC
authors: Larson
authors: Jared J
authors: JJ
authors: Diegmueller
authors: Jason H
authors: JH
authors: Ghodasra
authors: Erin L
authors: EL
authors: Hsu
mesh_terms: D000818:Animals; D064592:Autografts; D055396:Bone Morphogenetic Protein 2 / Q000008:administration & dosage / Q000633:toxicity*; D016025:Bone Transplantation; D016207:Cytokines / Q000097:blood; D005260:Female; D006801:Humans; D007085:Ilium / Q000637:transplantation; D018836:Inflammation Mediators / Q000097:blood; D008159:Lumbar Vertebrae / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000601:surgery*; D008279:Magnetic Resonance Imaging; D023421:Models, Animal; D010014:Osteolysis / Q000097:blood / Q000139:chemically induced*; D011916:Rats, Inbred F344; D011994:Recombinant Proteins / Q000633:toxicity; D049291:Seroma / Q000097:blood / Q000139:chemically induced* / Q000473:pathology; D013123:Spinal Fusion / Q000009:adverse effects; D015503:Surgical Sponges; D013997:Time Factors
chemical_list: C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; D016207:Cytokines; D018836:Inflammation Mediators; D011994:Recombinant Proteins