Bone Morphogenetic Proteins in Anterior Cervical Fusion: A Systematic Review and Meta-Analysis.
OBJECTIVE
Bone morphogenetic proteins (BMPs) have been commonly used as a graft substitute in spinal fusion. Although the U.S. Food and Drug Administration issued a warning on life-threatening complications of recombinant human BMPs (rhBMPs) in cervical spine fusion in 2008, their off-label use has been continued. This investigation aimed to review the evidence for the use of rhBMP-2 and rhBMP-7 in anterior cervical spine fusions.


METHODS
A comprehensive search was performed through Ovid (MEDLINE), PubMed, and Embase. The risk of bias assessment was according to the recommended criteria by the Cochrane Back and Neck group and MINORS (Methodological Index for Non-Randomized Studies). A wide array of radiographic and clinical outcomes including the adverse events were collated.


RESULTS
Eighteen articles (1 randomized and 17 nonrandomized) were eligible for inclusion. The fusion rate was higher with use of rhBMP in most studies and our meta-analysis of the pooled data from 4782 patients confirmed this finding (odds ratio, 5.45; P < 0.00001). Altogether, the rhBMP and control groups were comparable in patient-reported outcomes. However, most studies tended to show a significantly higher incidence of overall complication rate, dysphagia/dysphonia, cervical swelling, readmission, wound complications, neurologic complications, and ossification.


CONCLUSIONS
Application of rhBMPs in cervical spine fusion yields a significantly higher fusion rate with similar patient-reported outcomes, yet increased risk of life-threatening complications. Thus, we do not recommend the use of rhBMP in anterior cervical fusions.
Sina Trauma and Surgery Research Center, Tehran University of Medical Sciences (TUMS), Tehran, Iran.
Shayan Abdollah
SA
Zadegan
Sina Trauma and Surgery Research Center, Tehran University of Medical Sciences (TUMS), Tehran, Iran.
Aidin
A
Abedi
Sina Trauma and Surgery Research Center, Tehran University of Medical Sciences (TUMS), Tehran, Iran.
Seyed Behnam
SB
Jazayeri
Sina Trauma and Surgery Research Center, Tehran University of Medical Sciences (TUMS), Tehran, Iran.
Hirbod
H
Nasiri Bonaki
Sina Trauma and Surgery Research Center, Tehran University of Medical Sciences (TUMS), Tehran, Iran.
Seyed Behzad
SB
Jazayeri
Department of Orthopedics and Neurosurgery, The Rothman Institute at Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
Alexander R
AR
Vaccaro
Sina Trauma and Surgery Research Center, Tehran University of Medical Sciences (TUMS), Tehran, Iran. Electronic address: V_rahimi@sina.tums.ac.ir.
Vafa
V
Rahimi-Movaghar
D055396:Bone Morphogenetic Protein 2 / Q000009:adverse effects / Q000627:therapeutic use*; D055419:Bone Morphogenetic Protein 7 / Q000009:adverse effects / Q000627:therapeutic use*; D002574:Cervical Vertebrae / Q000601:surgery*; D006801:Humans; D056687:Off-Label Use; D016032:Randomized Controlled Trials as Topic; D011994:Recombinant Proteins / Q000009:adverse effects / Q000627:therapeutic use; D013123:Spinal Fusion / Q000379:methods*; D016212:Transforming Growth Factor beta / Q000009:adverse effects / Q000627:therapeutic use*
C525819:BMP7 protein, human; D055396:Bone Morphogenetic Protein 2; D055419:Bone Morphogenetic Protein 7; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; C499469:recombinant human bone morphogenetic protein-2
Bone morphogenetic proteins; Cervical vertebrae; Intervertebral disc; Spinal fusion