Bone repair in craniofacial defects treated with different doses of alendronate: a histological, histomorphometric, and immunohistochemical study

  • Naylin de Oliveira
  • Jefferson Oliveira
  • Letícia de Souza Moraes
  • Suyany Gabriely Weiss
  • Luís Henrique Chaves
  • Thais Costa Casagrande
  • Tatiana Miranda Deliberador
  • Allan Fernando Giovanini
  • João César Zielak
  • Rafaela ScariotEmail author
Original Article



The objective of the study is to evaluate bone repair in rats treated with different alendronate doses.

Matherials and methods

Sixty female rats ovariectomized were randomly divided in three groups: group C (control group), group A1 (ALN/1 mg/kg), and A2 (ALN/ 3 mg/kg). Each animal received subcutaneous applications of sodium alendronate at a dose correspondent to group A1 or A2 three times a week, while the control group received 0.9% saline solution. After 4 weeks of application, a critical defect was created in the calvaria of animals of all groups. The defect was filled by particulate autogenous bone. The applications were maintained until euthanasia, which occurred 15 and 60 days after the surgical procedure. The pieces were sent for histological, histomorphometric and immunohistochemical analysis. The data were submitted to statistical analysis with significance level of 0.05.


The descriptive histological analysis demonstrated an increase in bone neoformation in both groups treated with alendronate when compared to the control group. The histomorphometric analysis showed an increase in the amount of neoformed bone in A1 and A2 groups when compared to group C, both at 15 days (p = 0.0002) and at 60 days (p = 0.001). In the immunohistochemical analysis, it was possible to observe a difference in immunolabeling just for Mmp2 at the time of 60 days in A1 (p = 0.001) and A2 (p = 0.023) when compared to the control group.


Systemic delivery of alendronate, regardless of the dose, increased the amount of bone neoformation.

Clinical relevance

Prescription of sodium alendronate at 1 mg/kg for improvement of bone neoformation in bone graft procedures.


Alendronate Wnt3a protein Matrix metalloproteinase 2 Bone regeneration 


Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. All procedures performed in studies involving animals were in accordance with the ethical standards of the institution or practice at which the studies were conducted.

Informed consent

Not applicable.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Naylin de Oliveira
    • 1
  • Jefferson Oliveira
    • 1
  • Letícia de Souza Moraes
    • 1
  • Suyany Gabriely Weiss
    • 1
  • Luís Henrique Chaves
    • 1
  • Thais Costa Casagrande
    • 2
  • Tatiana Miranda Deliberador
    • 3
  • Allan Fernando Giovanini
    • 3
  • João César Zielak
    • 3
  • Rafaela Scariot
    • 3
    Email author
  1. 1.School of Health Sciences, Department of DentistryPositivo UniversityParanáBrazil
  2. 2.Master Program in BiotecnologyPositivo UniversityParanáBrazil
  3. 3.School of Health Sciences, Department of DentistryPositivo UniversityCuritibaBrazil

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