Bone repair in craniofacial defects treated with different doses of alendronate: a histological, histomorphometric, and immunohistochemical study
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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.
Prescription of sodium alendronate at 1 mg/kg for improvement of bone neoformation in bone graft procedures.
KeywordsAlendronate Wnt3a protein Matrix metalloproteinase 2 Bone regeneration
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
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.
- 3.Migliorati CA, Casiglia J, Epstein J, Jacobsen PL, Siegel MA, Woo SB. Managing the care of patients with bisphosphonate-associated osteonecrosis: an American Academy of Oral Medicine position paper. J Am Dent Assoc. 2005 Dec;136(12):1658–68. Review. Erratum in: J Am Dent Assoc. 2006 Jan;137(1):26CrossRefPubMedGoogle Scholar
- 5.Toker H, Ozdemir H, Ozer H, Eren K (2012) A comparative evaluation of the systemic and local alendronate treatment in synthetic bone graft: a histologic and histomorphometric study in a rat calvarial defect model. Oral Surg Oral Med Oral Pathol Oral Radiol 114(5 Suppl):S146–S152CrossRefPubMedGoogle Scholar
- 7.Burch J, Rice S, Yang H, Neilson A, Stirk L, Francis R et al. Systematic review of the use of bone turnover markers for monitoring the response to osteoporosis treatment: the secondary prevention of fractures, and primary prevention of fractures in high-risk groups. Health Technology Assessment 2014; 18 (11)Google Scholar
- 11.De Boer J, Wang HJ, Van Blitterswijk C. Effects of Wnt signaling on proliferation and differentiation of human mesenchymal stem cells. Tissue Eng 2004; 10(3–4):393–401Google Scholar
- 14.Nagase H, Woessner JF (1999) Matrix metalloproteinases. J Oral Chem 274:21491–21494Google Scholar
- 16.Zhao H, Bernardo MM, Osenkowski P, Sohail A, Pei D, Nagase H, Kashiwagi M, Soloway PD, DeClerck YA, Fridman R (2004) Differential inhibition of membrane type 3 (MT3)-matrix metalloproteinase (MMP) and MT1-MMP by tissue inhibitor of metalloproteinase (TIMP)-2 and TIMP-3 rgulates pro-MMP-2 activation. J Biol Chem 279(10):8592–8601 Epub 2003 Dec 16CrossRefPubMedGoogle Scholar
- 19.Buzza JA III, Einhorn T (2016) Bone healing in 2016. Clin Cases Miner Bone Metab 13(2):101–105Google Scholar
- 22.WHO technical report series, No. 843: (1994) Assessment of fracture risk and its application to screening for postmenopausal osteoporosis. Report of a WHO study group. Geneva: World Health OrganizationGoogle Scholar
- 23.Toker H, Ozdemir H, Ozer H, Eren K (2012) Alendronate enhances osseous healing in a rat calvarial defect model. Elsevier 57:1545–1550Google Scholar
- 24.Siebelt M, Waarsing JH, Groen HC, Müller C, Koelewijn SJ, de Blois E, Verhaar JAN, de Jong M, Weinans H (2014) Inhibited osteoclastic bone resorption through alendronate treatment in rats reduces severe osteoarthritis progression. Bone 66:163–170. https://doi.org/10.1016/j.bone.2014.06.009 CrossRefPubMedGoogle Scholar
- 29.De Simone E, Caggiano N, Polli M, Rolando J, Lastra Y, Gullace F et al (2013) Efecto del alendronato sobre el perfil de citoquinas y metaloproteinasas 2 y 9 en un modelo múrido de artritis experimental. Rev Colomb Reumatol 20(4):202–210Google Scholar