Retrospective Study
Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Orthop. Jan 18, 2017; 8(1): 36-41
Published online Jan 18, 2017. doi: 10.5312/wjo.v8.i1.36
Heterotopic ossification after the use of recombinant human bone morphogenetic protein-7
Marianthi Papanagiotou, Zoe H Dailiana, Theophilos Karachalios, Sokratis Varitimidis, Michael Hantes, Georgios Dimakopoulos, Marianna Vlychou, Konstantinos N Malizos
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
Georgios Dimakopoulos, Medical Statistics, Epirus Science and Technology Park, University of Ioannina Campus, 45500 Ioannina, Greece
Marianna Vlychou, Department of Radiology and Medical Imaging, Faculty of Medicine, University of Thessalia, 41500 Larissa, Greece
Author contributions: All the authors contributed to the manuscript.
Supported by The European Union (European Social Fund - ESF) and Greek national funds through the Operational Program “Education and Lifelong Learning” of the National Strategic Reference Framework (NSRF)-Research Funding Program: Heracleitus II.
Institutional review board statement: This study was reviewed and approved by the Educational Board of the University Hospital of Larissa, Greece.
Informed consent statement: Patients provided informed consent to receive the specific treatment. In the present study the analysis used anonymous clinical data that were obtained after each patient agreed to treatment by written consent.
Conflict-of-interest statement: We have no financial relationships to disclose.
Data sharing statement: No additional data on this topic are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Zoe H Dailiana, MD, PhD, Associate Professor, Department of Orthopaedic Surgery, Faculty of Medicine, University of Thessalia, 3 Panepistimiou St, Biopolis, 41500 Larissa, Greece. dailiana@med.uth.gr
Telephone: +30-24-13502722 Fax: +30-24-13501011
Received: June 13, 2016
Peer-review started: June 20, 2016
First decision: July 29, 2016
Revised: August 29, 2016
Accepted: October 25, 2016
Article in press: October 27, 2016
Published online: January 18, 2017
Abstract
AIM

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 χ2 test 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).

CONCLUSION

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.

Keywords: Nonunion, Bone morphogenetic protein, Recombinant human bone morphogenetic protein-7, Heterotopic ossification, Long bone, Bone graft, Osteoinduction

Core tip: Bone morphogenetic proteins are identified as factors promoting osteogenesis. In this study an attempt was made to estimate the rate of heterotopic bone formation in patients with long bone nonunions treated with recombinant human bone morphogenetic protein-7 (rhBMP-7), and to identify predisposing factors, related to the patient, the nonunion characteristics, and the surgical procedure. Eighteen percent of the patients developed heterotopic ossification on the radiographs, without functional limitations. All patients that developed heterotopic ossification were male. This rate of heterotopic ossification after rhBMP-7 use for the treatment of long bone nonunions is higher than the rates reported in literature.