title: RhBMP-2-induced radiculitis in patients undergoing transforaminal lumbar interbody fusion: relationship to dose.
abstract: Recombinant human bone morphogenetic protein-2 (rhBMP-2) remains the primary synthetic osteoinductive material used in spinal fusion surgery today. The early inflammation reaction to rhBMP-2 manifesting with radicular symptoms has been previously reported in patients undergoing transforaminal lumbar interbody fusion (TLIF). There is a disagreement with regard to the factors affecting its occurrence and whether such symptoms are dose dependent.
  
  
  
  The purpose of this analysis was to determine the incidence of rhBMP-2-induced radiculitis and its relationship to dose.
  
  
  
  A retrospective cohort analysis was performed of the prospectively collected data.
  
  
  
  All consecutive patients (n=204) who underwent one- or two-level TLIF and instrumented posterolateral fusion with an off-label rhBMP-2 use were included in this analysis.
  
  
  
  The patients who developed new radicular symptoms after initial improvement postoperatively and had sterile fluid collections indicative of inflammatory process, or in the absence of any structural abnormalities that would explain these symptoms on imaging studies, were deemed to have rhBMP-2-induced radiculitis.
  
  
  
  Magnetic resonance imaging (MRI) scans were obtained for all patients who developed postoperative radicular symptoms. Correlations between the total rhBMP-2 dose, dose per spinal level, and incidence of radiculitis were evaluated while controlling for age, sex, number of TLIF levels, and surgeon.
  
  
  
  The incidence of postoperative radiculitis was 11.3% (23 out of 204). The average total rhBMP-2 dose was 4.9 mg (range=2.1-12) and the average dose per spinal level was 3.8 mg (range=1.05-12). Logistic regression analysis did not identify any significant correlations between the rhBMP-2 doses and the incidence of radiculitis (p=.6).
  
  
  
  The incidence of rhBMP-2-induced radiculitis in patients undergoing TLIF is quite high, but there were no dose-related correlations found. The study, however, cannot rule out a possibility that a larger variation in bone morphogenetic protein (BMP) doses could still be a factor in the development of rhBMP-2-associated radiculitis.
authors.affiliation: Boulder Neurosurgical Associates, 4743 Arapahoe Ave, Suite 202, Boulder, CO 80303, USA; Justin Parker Neurological Institute, 4743 Arapahoe Ave, Suite 202, Boulder, CO 80303, USA.
authors.forename: Alan T
authors.initials: AT
authors.lastname: Villavicencio
authors.affiliation: Boulder Neurosurgical Associates, 4743 Arapahoe Ave, Suite 202, Boulder, CO 80303, USA; Justin Parker Neurological Institute, 4743 Arapahoe Ave, Suite 202, Boulder, CO 80303, USA. Electronic address: sigitab@bnasurg.com.
authors.forename: Sigita
authors.initials: S
authors.lastname: Burneikiene
mesh_terms: D000328:Adult; D000368:Aged; D055396:Bone Morphogenetic Protein 2 / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008159:Lumbar Vertebrae / Q000601:surgery; D008297:Male; D008875:Middle Aged; D011843:Radiculopathy / Q000209:etiology*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D012189:Retrospective Studies; D013123:Spinal Fusion / Q000009:adverse effects / Q000379:methods*; D016212:Transforming Growth Factor beta / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use
chemical_list: D055396:Bone Morphogenetic Protein 2; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; C499469:recombinant human bone morphogenetic protein-2
keywords: Complications; Incidence; Radiculitis; Recombinant human bone morphogenetic protein-2; RhBMP-2; Transforaminal lumbar interbody fusion