title: Bone substitutes and expanders in Spine Surgery: A review of their fusion efficacies.
abstract: METHODS
  A narrative review of literature.
  
  
  OBJECTIVE
  This manuscript intends to provide a review of clinically relevant bone substitutes and bone expanders for spinal surgery in terms of efficacy and associated clinical outcomes, as reported in contemporary spine literature.
  
  
  BACKGROUND
  Ever since the introduction of allograft as a substitute for autologous bone in spinal surgery, a sea of literature has surfaced, evaluating both established and newly emerging fusion alternatives. An understanding of the available fusion options and an organized evidence-based approach to their use in spine surgery is essential for achieving optimal results.
  
  
  METHODS
  A Medline search of English language literature published through March 2016 discussing bone graft substitutes and fusion extenders was performed. All clinical studies reporting radiological and/or patient outcomes following the use of bone substitutes were reviewed under the broad categories of Allografts, Demineralized Bone Matrices (DBM), Ceramics, Bone Morphogenic proteins (BMPs), Autologous growth factors (AGFs), Stem cell products and Synthetic Peptides. These were further grouped depending on their application in lumbar and cervical spine surgeries, deformity correction or other miscellaneous procedures viz. trauma, infection or tumors; wherever data was forthcoming. Studies in animal populations and experimentalin vitrostudies were excluded. Primary endpoints were radiological fusion rates and successful clinical outcomes.
  
  
  RESULTS
  A total of 181 clinical studies were found suitable to be included in the review. More than a third of the published articles (62 studies, 34.25%) focused on BMP. Ceramics (40 studies) and Allografts (39 studies) were the other two highly published groups of bone substitutes. Highest radiographic fusion rates were observed with BMPs, followed by allograft and DBM. There were no significant differences in the reported clinical outcomes across all classes of bone substitutes.
  
  
  CONCLUSIONS
  There is a clear publication bias in the literature, mostly favoring BMP. Based on the available data, BMP is however associated with the highest radiographic fusion rate. Allograft is also very well corroborated in the literature. The use of DBM as a bone expander to augment autograft is supported, especially in the lumbar spine. Ceramics are also utilized as bone graft extenders and results are generally supportive, although limited. The use of autologous growth factors is not substantiated at this time. Cell matrix or stem cell-based products and the synthetic peptides have inadequate data. More comparative studies are needed to evaluate the efficacy of bone graft substitutes overall.
authors.affiliation: Pennsylvania Hospital of the University of Pennsylvania Health System, Philadelphia, PA.
authors.forename: Abhijeet
authors.initials: A
authors.lastname: Kadam
authors.affiliation: Rothman Institute, Philadelphia, PA.
authors.forename: Paul W
authors.initials: PW
authors.lastname: Millhouse
authors.affiliation: Rothman Institute, Philadelphia, PA.
authors.forename: Christopher K
authors.initials: CK
authors.lastname: Kepler
authors.affiliation: Rothman Institute, Philadelphia, PA.
authors.forename: Kris E
authors.initials: KE
authors.lastname: Radcliff
authors.affiliation: Toronto Western Hospital, Toronto, Canada.
authors.forename: Michael G
authors.initials: MG
authors.lastname: Fehlings
authors.affiliation: Center for Spine & Orthopaedics, Denver, CO.
authors.forename: Michael E
authors.initials: ME
authors.lastname: Janssen
authors.affiliation: Indiana Spine Group, Indianapolis, IN.
authors.forename: Rick C
authors.initials: RC
authors.lastname: Sasso
authors.affiliation: Cerapedics, Westminster, CO.
authors.forename: James J
authors.initials: JJ
authors.lastname: Benedict
authors.affiliation: Rothman Institute, Philadelphia, PA.
authors.forename: Alexander R
authors.initials: AR
authors.lastname: Vaccaro
keywords: allografts; autologous growth factors; bone substitutes; ceramics; demineralized bone matrix (dbm); hydroxyapatite; i-factor; osteogenic protein-1 (op-1); rhbmp-2; spine fusion; synthetic peptides; β tricalcium phosphate (β-tcp)