Journal of Bone and Mineral Metabolism

, Volume 33, Issue 5, pp 496–506 | Cite as

What is the role of bosentan in healing of femur fractures in a rat model?

  • Ali Aydin
  • Zekai HaliciEmail author
  • Erol Akpinar
  • A. Murat Aksakal
  • Murat Saritemur
  • Muhammed Yayla
  • C. Semih Kunak
  • Elif Cadirci
  • H. Tarik Atmaca
  • S. Sena Karcioglu
Original Article


The purpose of this study was to examine the effects bosentan (which is a strong vasoconstrictor) on bone fracture pathophysiology, and investigate the roles of the nonselective endothelin 1 receptor blocker bosentan on the bone fractures formed in rats through radiographic, histopathologic, and immunohistochemical methods. The rats were divided into three groups (six rats in each group): a femoral fracture control group, a femoral fracture plus bosentan at 50 mg/kg group, and a femoral fracture plus bosentan at 100 mg/kg group. The femoral fracture model was established by transversely cutting the femur at the midsection. After manual reduction, the fractured femur was fixed with intramedullary Kirschner wires. The radiographic healing scores of the bosentan 100 and 50 mg/kg groups were significantly better that those of the fracture control group. The fracture callus percent of new bone in the bosentan 100 mg/kg group was significantly greater than that in the control group. Also, semiquantitative analysis showed higher positive vascular endothelial growth factor and osteocalcin staining and lower positive endothelin receptor type A staining in the treatment groups than in the control group. Bosentan treatment also decreased tissue endothelin 1 expression relative to that in the fracture control group. As a result of our study, the protective effect of bosentan was shown in experimental femoral fracture healing in rats by radiographic, histopathologic, and molecular analyses.


Bosentan Endothelin 1 Bone fracture Rat Femur 



We thank Marc Iglarz and Actelion Pharmaceuticals Ltd for providing us with bosentan. This work was supported by the Ataturk University Medical Research Council (grant number 2012/03).

Conflict of interest

None of the authors has a commercial interest, financial interest, and/or other relationship with the manufacturers of pharmaceuticals, laboratory supplies, and/or medical devices, or with commercial providers of medically related services.


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Copyright information

© The Japanese Society for Bone and Mineral Research and Springer Japan 2014

Authors and Affiliations

  • Ali Aydin
    • 1
  • Zekai Halici
    • 2
    Email author
  • Erol Akpinar
    • 2
  • A. Murat Aksakal
    • 3
  • Murat Saritemur
    • 4
  • Muhammed Yayla
    • 2
  • C. Semih Kunak
    • 5
  • Elif Cadirci
    • 6
  • H. Tarik Atmaca
    • 7
  • S. Sena Karcioglu
    • 2
  1. 1.Department of Orthopedics and TraumatologyAtaturk University Faculty of MedicineErzurumTurkey
  2. 2.Department of PharmacologyAtaturk University Faculty of MedicineErzurumTurkey
  3. 3.Department of Orthopedics and TraumathologySevket Yilmaz Education and Research HospitalBursaTurkey
  4. 4.Department of Emergency MedicineAtaturk University Faculty of PharmacyErzurumTurkey
  5. 5.Department of PharmacologyOrdu University Faculty of MedicineOrduTurkey
  6. 6.Department of PharmacologyAtaturk University Faculty of PharmacyErzurumTurkey
  7. 7.Department of PathologyKırıkkale University Faculty of VeterinaryKırıkkaleTurkey

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