title: Complications related to osteobiologics use in spine surgery: a systematic review.
abstract: METHODS
  Systematic review.
  
  
  OBJECTIVE
  The objectives of this systematic review were to identify the character and rates of complications in patients after the use of BMP in spine fusion surgery and to determine whether there is a dose-response relationship of BMP with complications.
  
  
  BACKGROUND
  BMP is used on-label for ALIF with LT-CAGE and off-label for various spine fusion applications in the cervical, thoracic, and lumbar spines because of its effectiveness in promoting arthrodesis. Multiple studies published over the past several years have highlighted complications associated with BMP in a variety of clinical fusion scenarios. There are no systematic reviews on this topic, and thus, the complication profile of off-label use or physician directed use of BMP in spinal fusion surgery is not well characterized. Some of the reported complications are unique to BMP, which underscores the need for this thorough literature review.
  
  
  METHODS
  A systematic review of the English language literature was performed for articles published between 1990 and June 2009. Electronic databases and reference lists of key articles were searched to identify articles examining the use of BMP in spine surgery. Two independent reviewers assessed the level of evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria and disagreements were resolved by consensus.
  
  
  RESULTS
  Two hundred forty-' articles that assessed outcomes after BMP use in spinal surgery were identified from the literature; of these, 31 articles were selected for inclusion. We determined that multiple complications are associated after the use of rhBMP-2 in both cervical and lumbar spine fusion surgery. There is a mean incidence of 44%, 25%, and 27% of resorption, subsidence, and interbody cage migration reported for lumbar spine interbody fusion surgery although reoperation or long-term detrimental effect was rare. Cervical studies report a mean 5.8% of postoperative soft tissue problems, including dysphagia, when rhBMP-2 is used for ventral cervical fusion. It was determined that the strength of evidence of the peer-reviewed literature that report on types of complications is high for the lumbar and low for the cervical spine, respectively, and that the current strength of evidence on rates of complications with BMP is moderate and low, respectively.
  
  
  CONCLUSIONS
  The complication profile of BMP-2 for ALIF with LT-CAGE is well characterized. Because of the lack of substantive data, the same is not true for other types of lumbar fusions, or for cervical or thoracic fusion applications. BMP has been associated with a variety of unique complications in the ventral cervical and lumbar spines. The published data on BMP fail to precisely profile this product's use in fusion surgery; hence, it should be used only after a careful consideration of the relevant data. Well-designed and executed studies are necessary to completely define the incidence of various complications relative to type of BMP, type and region of fusion, surgical technique, dose, and carrier, and importantly, to define the natural history and management of associated complications.
authors.affiliation: Neurological Institute, Center for Spine Health, Departments of Orthopaedic and Neurological Surgery, The Cleveland Clinic, Cleveland, OH 44195, USA. mrozt@ccf.org
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Mroz
authors.forename: Jeffrey C
authors.initials: JC
authors.lastname: Wang
authors.forename: Robin
authors.initials: R
authors.lastname: Hashimoto
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Norvell
mesh_terms: D019485:Bone Morphogenetic Proteins / Q000009:adverse effects*; D001861:Bone Regeneration / Q000187:drug effects / Q000502:physiology; D004868:Equipment Failure / Q000706:statistics & numerical data; D006801:Humans; D015994:Incidence; D016268:Internal Fixators / Q000009:adverse effects; D011183:Postoperative Complications / Q000139:chemically induced* / Q000453:epidemiology* / Q000503:physiopathology; D011993:Recombinant Fusion Proteins / Q000009:adverse effects; D013122:Spinal Diseases / Q000601:surgery*; D013123:Spinal Fusion / Q000009:adverse effects* / Q000379:methods; D013131:Spine / Q000187:drug effects / Q000473:pathology / Q000601:surgery
chemical_list: D019485:Bone Morphogenetic Proteins; D011993:Recombinant Fusion Proteins