title: Development of a Model System to Evaluate Local Recurrence in Osteosarcoma and Assessment of the Effects of Bone Morphogenetic Protein-2.
abstract: OBJECTIVE
  It is increasingly relevant to better define what constitutes an adequate surgical margin in an effort to improve reconstructive longevity and functional outcomes following osteosarcoma surgery. In addition, nonunion remains a challenging problem in some patients following allograft reconstruction. Bone morphogenetic protein-2 (BMP-2) could enhance osseous union, but has been historically avoided due to concerns that it may promote tumor recurrence.
  
  
  METHODS
  An orthotopic xenograft murine model was utilized to describe the natural temporal course of osteosarcoma growth. Tumors were treated either with surgery alone, surgery and single-agent chemotherapy, or surgery and dual-agent chemotherapy to assess the relationship between surgical margin and local recurrence. The effect of BMP-2 on local recurrence was similarly assessed.
  
  
  RESULTS
  Osteosarcoma tumor growth was categorized into reproducible phases. Margins greater than 997 μm resulted in local control following surgery alone. Margins greater than 36 μm resulted in local control following surgery and single-agent chemotherapy. Margins greater than 12 μm resulted in local control following surgery and dual-agent chemotherapy. The application of exogenous BMP-2 does not confer an increased risk of local recurrence.
  
  
  CONCLUSIONS
  This model reliably reproduces the clinical, radiographic, and surgical conditions encountered in human osteosarcoma. It successfully incorporates relevant chemotherapy, further paralleling the human experience. Surgical margins required to achieve local control in osteosarcoma can be reduced using single-agent chemotherapy and further decreased using dual-agent chemotherapy. The application of BMP-2 does not increase local recurrence in this model.
authors.affiliation: Department of Orthopaedic Surgery, Montefiore Medical Center and The Children's Hospital at Montefiore, Bronx, New York. Department of Pediatrics, Montefiore Medical Center and The Children's Hospital at Montefiore, Bronx, New York. Albert Einstein College of Medicine, Bronx, New York. dgeller@montefiore.org.
authors.forename: David S
authors.initials: DS
authors.lastname: Geller
authors.affiliation: Department of Pediatrics, Montefiore Medical Center and The Children's Hospital at Montefiore, Bronx, New York. Albert Einstein College of Medicine, Bronx, New York.
authors.forename: Michael Y
authors.initials: MY
authors.lastname: Singh
authors.affiliation: Department of Pediatrics, Montefiore Medical Center and The Children's Hospital at Montefiore, Bronx, New York. Albert Einstein College of Medicine, Bronx, New York.
authors.forename: Wendong
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Pediatrics, Montefiore Medical Center and The Children's Hospital at Montefiore, Bronx, New York. Albert Einstein College of Medicine, Bronx, New York.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Gill
authors.affiliation: Department of Pediatrics, Montefiore Medical Center and The Children's Hospital at Montefiore, Bronx, New York. Albert Einstein College of Medicine, Bronx, New York.
authors.forename: Michael E
authors.initials: ME
authors.lastname: Roth
authors.affiliation: Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York.
authors.forename: Mimi Y
authors.initials: MY
authors.lastname: Kim
authors.affiliation: Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York.
authors.forename: Xianhong
authors.initials: X
authors.lastname: Xie
authors.affiliation: Department of Orthopaedic Surgery, Montefiore Medical Center and The Children's Hospital at Montefiore, Bronx, New York. Albert Einstein College of Medicine, Bronx, New York.
authors.forename: Christopher K
authors.initials: CK
authors.lastname: Singh
authors.affiliation: Department of Orthopaedic Surgery, Montefiore Medical Center and The Children's Hospital at Montefiore, Bronx, New York. Albert Einstein College of Medicine, Bronx, New York.
authors.forename: Howard D
authors.initials: HD
authors.lastname: Dorfman
authors.affiliation: Albert Einstein College of Medicine, Bronx, New York. Department of Pathology, Montefiore Medical Center, Bronx, New York.
authors.forename: Esperanza
authors.initials: E
authors.lastname: Villanueva-Siles
authors.affiliation: Department of Pediatrics, Montefiore Medical Center and The Children's Hospital at Montefiore, Bronx, New York.
authors.forename: Amy
authors.initials: A
authors.lastname: Park
authors.affiliation: Department of Pediatrics, Montefiore Medical Center and The Children's Hospital at Montefiore, Bronx, New York.
authors.forename: Sajida
authors.initials: S
authors.lastname: Piperdi
authors.affiliation: Department of Pediatrics, Montefiore Medical Center and The Children's Hospital at Montefiore, Bronx, New York. Albert Einstein College of Medicine, Bronx, New York. Department of Molecular Pharmocology, Albert Einstein College of Medicine, Bronx, New York.
authors.forename: Richard
authors.initials: R
authors.lastname: Gorlick
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology* / Q000627:therapeutic use; D055396:Bone Morphogenetic Protein 2 / Q000494:pharmacology* / Q000502:physiology; D001859:Bone Neoplasms / Q000473:pathology* / Q000628:therapy; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D016513:Mice, SCID; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis / Q000517:prevention & control*; D012516:Osteosarcoma / Q000473:pathology* / Q000628:therapy; D012372:ROC Curve; D023041:Xenograft Model Antitumor Assays
chemical_list: D055396:Bone Morphogenetic Protein 2