title: Heterotopic ossification after the use of recombinant human bone morphogenetic protein-7.
abstract: OBJECTIVE
  To present the incidence of heterotopic ossification after the use of recombinant human bone morphogenetic protein-7 (rhBMP-7) for the treatment of nonunions.
  
  
  METHODS
  Bone morphogenetic proteins (BMPs) promote bone formation by auto-induction. Recombinant human BMP-7 in combination with bone grafts was used in 84 patients for the treatment of long bone nonunions. All patients were evaluated radiographicaly for the development of heterotopic ossification during the standard assessment for the nonunion healing. In all patients (80.9%) with radiographic signs of heterotopic ossification, a CT scan was performed. Nonunion site palpation and ROM evaluation of the adjacent joints were also carried out. Factors related to the patient (age, gender), the nonunion (location, size, chronicity, number of previous procedures, infection, surrounding tissues condition) and the surgical procedure (graft and fixation type, amount of rhBMP-7) were correlated with the development of heterotopic ossification and statistical analysis with Pearsons χ2test was performed.
  
  
  RESULTS
  Eighty point nine percent of the nonunions treated with rhBMP-7, healed with no need for further procedures. Heterotopic bone formation occurred in 15 of 84 patients (17.8%) and it was apparent in the routine radiological evaluation of the nonunion site, in a mean time of 5.5 mo after the rhBMP-7 application (range 3-12). The heterotopic ossification was located at the femur in 8 cases, at the tibia in 6, and at the humerus in οne patient. In 4 patients a palpable mass was present and only in one patient, with a para-articular knee nonunion treated with rhBMP-7, the size of heterotopic ossification affected the knee range of motion. All the patients with heterotopic ossification were male. Statistical analysis proved that patient's gender was the only important factor for the development of heterotopic ossification (P= 0.007).
  
  
  CONCLUSIONS
  Heterotopic ossification after the use of rhBMP-7 in nonunions was common but it did not compromise the final clinical outcome in most cases, and affected only male patients.
authors.affiliation: Marianthi Papanagiotou, Zoe H Dailiana, Theophilos Karachalios, Sokratis Varitimidis, Michael Hantes, Konstantinos N Malizos, Department of Orthopaedic Surgery, Faculty of Medicine, University of Thessalia, 41500 Larissa, Greece.
authors.forename: Marianthi
authors.initials: M
authors.lastname: Papanagiotou
authors.affiliation: Marianthi Papanagiotou, Zoe H Dailiana, Theophilos Karachalios, Sokratis Varitimidis, Michael Hantes, Konstantinos N Malizos, Department of Orthopaedic Surgery, Faculty of Medicine, University of Thessalia, 41500 Larissa, Greece.
authors.forename: Zoe H
authors.initials: ZH
authors.lastname: Dailiana
authors.affiliation: Marianthi Papanagiotou, Zoe H Dailiana, Theophilos Karachalios, Sokratis Varitimidis, Michael Hantes, Konstantinos N Malizos, Department of Orthopaedic Surgery, Faculty of Medicine, University of Thessalia, 41500 Larissa, Greece.
authors.forename: Theophilos
authors.initials: T
authors.lastname: Karachalios
authors.affiliation: Marianthi Papanagiotou, Zoe H Dailiana, Theophilos Karachalios, Sokratis Varitimidis, Michael Hantes, Konstantinos N Malizos, Department of Orthopaedic Surgery, Faculty of Medicine, University of Thessalia, 41500 Larissa, Greece.
authors.forename: Sokratis
authors.initials: S
authors.lastname: Varitimidis
authors.affiliation: Marianthi Papanagiotou, Zoe H Dailiana, Theophilos Karachalios, Sokratis Varitimidis, Michael Hantes, Konstantinos N Malizos, Department of Orthopaedic Surgery, Faculty of Medicine, University of Thessalia, 41500 Larissa, Greece.
authors.forename: Michael
authors.initials: M
authors.lastname: Hantes
authors.affiliation: Marianthi Papanagiotou, Zoe H Dailiana, Theophilos Karachalios, Sokratis Varitimidis, Michael Hantes, Konstantinos N Malizos, Department of Orthopaedic Surgery, Faculty of Medicine, University of Thessalia, 41500 Larissa, Greece.
authors.forename: Georgios
authors.initials: G
authors.lastname: Dimakopoulos
authors.affiliation: Marianthi Papanagiotou, Zoe H Dailiana, Theophilos Karachalios, Sokratis Varitimidis, Michael Hantes, Konstantinos N Malizos, Department of Orthopaedic Surgery, Faculty of Medicine, University of Thessalia, 41500 Larissa, Greece.
authors.forename: Marianna
authors.initials: M
authors.lastname: Vlychou
authors.affiliation: Marianthi Papanagiotou, Zoe H Dailiana, Theophilos Karachalios, Sokratis Varitimidis, Michael Hantes, Konstantinos N Malizos, Department of Orthopaedic Surgery, Faculty of Medicine, University of Thessalia, 41500 Larissa, Greece.
authors.forename: Konstantinos N
authors.initials: KN
authors.lastname: Malizos
keywords: Bone graft; Bone morphogenetic protein; Heterotopic ossification; Long bone; Nonunion; Osteoinduction; Recombinant human bone morphogenetic protein-7