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BMC Musculoskeletal Disorders
Published in: BMC Musculoskeletal Disorders 1/2018

Open Access 01-12-2018 | Research article

Bone morphogenetic proteins − 7 and − 2 in the treatment of delayed osseous union secondary to bacterial osteitis in a rat model

Authors: Lars Helbig, Georg W. Omlor, Adriana Ivanova, Thorsten Guehring, Robert Sonntag, J. Philippe Kretzer, Susann Minkwitz, Britt Wildemann, Gerhard Schmidmaier

Published in: BMC Musculoskeletal Disorders | Issue 1/2018

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Abstract

Background

Bone infections due to trauma and subsequent delayed or impaired fracture healing represent a great challenge in orthopedics and trauma surgery. The prevalence of such bacterial infection-related types of delayed non-union is high in complex fractures, particularly in open fractures with additional extensive soft-tissue damage. The aim of this study was to establish a rat model of delayed osseous union secondary to bacterial osteitis and investigate the impact of rhBMP-7 and rhBMP-2 on fracture healing in the situation of an ongoing infection.

Methods

After randomization to four groups 72 Sprague-Dawley rats underwent a transverse fracture of the midshaft tibia stabilized by intramedullary titanium K-wires. Three groups received an intramedullary inoculation with Staphylococcus aureus (103 colony-forming units) before stabilization and the group without bacteria inoculation served as healing control. After 5 weeks, a second surgery was performed with irrigation of the medullary canal and local rhBMP-7 and rhBMP-2 treatment whereas control group and infected control group received sterile saline. After further 5 weeks rats were sacrificed and underwent biomechanical testing to assess the mechanical stability of the fractured bone. Additional micro-CT analysis, histological, and histomorphometric analysis were done to evaluate bone consolidation or delayed union, respectively, and to quantify callus formation and the mineralized area of the callus.

Results

Biomechanical testing showed a significantly higher fracture torque in the non-infected control group and the infected rhBMP-7- and rhBMP-2 group compared with the infected control group (p < 0.001). RhBMP-7 and rhBMP-2 groups did not show statistically significant differences (p = 0.57). Histological findings supported improved bone-healing after rhBMP treatment but quantitative micro-CT and histomorphometric results still showed significantly more hypertrophic callus tissue in all three infected groups compared to the non-infected group. Results from a semiquantitative bone-healing-score revealed best bone-healing in the non-infected control group. The expected chronic infection was confirmed in all infected groups.

Conclusions

In delayed bone healing secondary to infection rhBMP treatment promotes bone healing with no significant differences in the healing efficacy of rhBMP-2 and rhBMP-7 being noted. Further new therapeutic bone substitutes should be analyzed with the present rat model for delayed osseous union secondary to bacterial osteitis.
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Metadata
Title
Bone morphogenetic proteins − 7 and − 2 in the treatment of delayed osseous union secondary to bacterial osteitis in a rat model
Authors
Lars Helbig
Georg W. Omlor
Adriana Ivanova
Thorsten Guehring
Robert Sonntag
J. Philippe Kretzer
Susann Minkwitz
Britt Wildemann
Gerhard Schmidmaier
Publication date
01-12-2018
Publisher
BioMed Central
Published in
BMC Musculoskeletal Disorders / Issue 1/2018
Electronic ISSN: 1471-2474
DOI
https://doi.org/10.1186/s12891-018-2203-7

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