Advertisement

Oral and Maxillofacial Surgery

, Volume 23, Issue 4, pp 473–479 | Cite as

Imaging and histomorphometric evaluation of mandible and tibia of rats treated with bisphosphonates

  • Stephanie Joana Roman Martelli
  • Melissa Feres Damian
  • André Ribeiro Schinestsck
  • Lauren Frenzel Schuch
  • Andreia Morales Cascaes
  • Ana Carolina Uchoa VasconcelosEmail author
Original Article
  • 38 Downloads

Abstract

Objectives

To evaluate the mandible and tibia of rats treated with bisphosphonates (BPs) by imaging and histomorphometric analysis.

Study design

Thirty-four rat specimens (Rattus norvegicus, Wistar strain) were distributed into 3 groups: (1) 12 rats treated with zoledronic acid; (2) 12 rats treated with clodronate; and (3) the control group, containing 10 rats that received saline. All bones were exposed to cone beam computed tomography (CBCT). The images were analyzed to determine bone density (BD), using the software OsiriX 7.0. Histological slides were prepared from the specimens and the proportion of bone volume (BV) was quantified using the software Adobe Photoshop CC.

Results

There was no statistically significant difference in BD either between the drug groups or between mandible and tibia. BV between BPs and control group did not show a significant difference. However, comparing the two bones, the mandibles in the control group displayed higher BV than did the tibiae in the same group.

Conclusion

According to our results, we conclude that (1) BD was not altered by bone type or by type of BP administered, and (2) treatment with zoledronic acid or clodronate did not affect BV in the mandible or tibia of test groups.

Keywords

Bisphosphonate Cone-beam computed tomography Jaws Bone tissue Bisphosphonate-associated osteonecrosis of the jaw 

Notes

Acknowledgments

This study received financial support from the National Council for Scientific and Technological Development (CNPq), and Center of Diagnosis of Oral Diseases and Federal University of Pelotas for the use of facilities and equipment. LFS was granted with fellowship provided by Coordenação de Aperfeiçoamento de Pessoal de Nível Superior – Brazil (CAPES) – Finance code 001. Dr. A. Leyva (USA) helped with the English editing of the manuscript.

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.

Informed consent

This article does not contain any studies with human participants performed by any of the authors.

References

  1. 1.
    Allen MR (2015) Medication-related osteonecrosis of the jaw: basic and translational science updates. Oral Maxillofac Surg Clin North Am 27:497–508.  https://doi.org/10.1016/j.coms.2015.06.002 CrossRefGoogle Scholar
  2. 2.
    Oyhanart SR, Escudero ND, Mandalunis PM (2015) Effect of alendronate on the mandible and long bones: an experimental study in vivo. Pediatr Res 78:618–625.  https://doi.org/10.1038/pr.2015.163 CrossRefPubMedGoogle Scholar
  3. 3.
    Rezende E, Bradaschia-Correa V, Siviero F, Ambrosio LMB, Arana-Chavez VE (2017) Effects of bisphosphonates on osteogenesis and osteoclastogenesis signaling during the endochondral ossification of growing rats. Cell Tissue Res 368:287–300.  https://doi.org/10.1007/s00441-017-2574-3 CrossRefPubMedGoogle Scholar
  4. 4.
    Vasconcelos AC, Berti-Couto SA, Azambuja AA et al (2012) Comparison of effects of clodronate and zoledronic acid on the repair of maxilla surgical wounds - histomorphometric, receptor activator of nuclear factor-kB ligand, osteoprotegerin, von Willebrand factor, and caspase-3 evaluation. J Oral Pathol Med 41:702–712.  https://doi.org/10.1111/j.1600-0714.2012.01140.x CrossRefPubMedGoogle Scholar
  5. 5.
    Sigua-Rodriguez EA, da Costa Ribeiro R, de Brito AC, Alvarez-Pinzon N, de Albergaria-Barbosa JR (2014) Bisphosphonate-related osteonecrosis of the jaw: a review of the literature. Int J Dent 2014:192320.  https://doi.org/10.1155/2014/192320 CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Fleisher K, Kontio R, Otto S (2016) Antiresorptive drug-related osteonecrosis of the jaw (ARONJ) – a guide to research, 1st edn. AOCMFGoogle Scholar
  7. 7.
    Russell RG (2007) Bisphosphonates: mode of action and pharmacology. Pediatrics 119:S150–S162CrossRefGoogle Scholar
  8. 8.
    Marx RE (2003) Pamidronate (Aredia) and zoledronate (Zometa) induced avascular necrosis of the jaws: a growing epidemic. J Oral Maxillofac Surg 61:1115–1117CrossRefGoogle Scholar
  9. 9.
    Ruggiero SL, Dodson TB, Fantasia J, Goodday R, Aghaloo T, Mehrotra B, O’Ryan F, American Association of Oral and Maxillofacial Surgeons (2014) American Association of Oral and Maxillofacial Surgeons position paper on medication-related osteonecrosis of the jaw--2014 update. J Oral Maxillofac Surg 72:1938–1956.  https://doi.org/10.1016/j.joms.2014.04.031 CrossRefPubMedGoogle Scholar
  10. 10.
    Khan AA, Morrison A, Hanley DA, Hashem W, Compston J (2016) Diagnosis and management of osteonecrosis of the jaw: a systematic review and international consensus. Osteoporos Int 27:853–859.  https://doi.org/10.1007/s00198-015-3335-3 CrossRefPubMedGoogle Scholar
  11. 11.
    Ruggiero SL (2015) Diagnosis and staging of medication-related osteonecrosis of the jaw. Oral Maxillofac Surg Clin North Am 27:479–487.  https://doi.org/10.1016/j.coms.2015.06.008 CrossRefPubMedGoogle Scholar
  12. 12.
    Hamada H, Matsuo A, Koizumi T, Satomi T, Chikazu D (2014) A simple evaluation method for early detection of bisphosphonate-related osteonecrosis of the mandible using computed tomography. J Craniomaxillofac Surg 42:924–929.  https://doi.org/10.1016/j.jcms.2014.01.012 CrossRefPubMedGoogle Scholar
  13. 13.
    Eleutherakis-Papaiakovou E, Bamias A (2017) Antiresorptive treatment-associated ONJ. Eur J Cancer Care 26(6):e12787.  https://doi.org/10.1111/ecc.12787 CrossRefGoogle Scholar
  14. 14.
    Anderson PJ, Yong R, Surman TL, Rajion ZA, Ranjitkar S (2014) Application of three-dimensional computed tomography in craniofacial clinical practice and research. Aust Dent J 59:174–185.  https://doi.org/10.1111/adj.12154 CrossRefPubMedGoogle Scholar
  15. 15.
    Cankaya AB, Erdem MA, Isler SC, Demircan S, Soluk M, Kasapoglu C, Oral CK (2011) Use of cone-beam computerized tomography for evaluation of bisphosphonate-associated osteonecrosis of the jaws in an experimental rat model. Int J Med Sci 8:667–672CrossRefGoogle Scholar
  16. 16.
    Maahs MP, Azambuja AA, Campos MM, Salum FG, Cherubini K (2011) Association between bisphosphonates and jaw osteonecrosis: a study in Wistar rats. Head Neck 33:199–207.  https://doi.org/10.1002/hed.21422 CrossRefPubMedGoogle Scholar
  17. 17.
    Barba-Recreo P, Del Castillo Pardo de Vera JL, Garcia-Arranz M, Yebenes L, Burgueno M (2014) Zoledronic acid - related osteonecrosis of the jaws. Experimental model with dental extractions in rats. J Craniomaxillofac Surg 42:744–750.  https://doi.org/10.1016/j.jcms.2013.11.005 CrossRefPubMedGoogle Scholar
  18. 18.
    Gong X, Yu W, Zhao H, Su J, Sheng Q (2017) Skeletal site-specific effects of zoledronate on in vivo bone remodeling and in vitro BMSCs osteogenic activity. Sci Rep 31:36129.  https://doi.org/10.1038/srep36129 CrossRefGoogle Scholar
  19. 19.
    Macerata R (2002) Zometa (zoledronic acid)—intravenous formulation. Investigator’s brochure for consultation. 8th ed.Google Scholar
  20. 20.
    Turner PV, Brabb T, Pekow C, Vasbinder MA (2011) Administration of substances to laboratory animals: routes of administration and factors to consider. J Am Assoc Lab Anim Sci 50:600–613PubMedPubMedCentralGoogle Scholar
  21. 21.
    Mahl C, Fontoura F, Borelli P, Silva I, Fontanella V (2009) Mandible’s radiographic and histomorphometric assessment in female rats medicated with glucocorticoid and biphosphonate. Rev Facul Odontol Porto Alegre 50:16–19Google Scholar
  22. 22.
    Taniguchi T, Ariji Y, Nozawa M, Naitoh M, Kuroiwa Y, Kurita K, Ariji E (2016) Computed tomographic assessment of early changes of the mandible in bisphosphonate-treated patients. Oral Surg Oral Med Oral Pathol Oral Radiol 122:362–372.  https://doi.org/10.1016/j.oooo.2016.06.002 CrossRefPubMedGoogle Scholar
  23. 23.
    Gönen ZB, Yillmaz Asan C, Zararsiz G, Kilic E, Alkan A (2018) Osseous changes in patients with medication-related osteonecrosis of the jaws. Dentomaxillofac Radiol 47:20170172.  https://doi.org/10.1259/dmfr.20170172 CrossRefPubMedGoogle Scholar
  24. 24.
    Torres SR, Chen CS, Leroux BG et al (2012) Mandibular cortical bone evaluation on cone beam computed tomography images of patients with bisphosphonate-related osteonecrosis of the jaw. Oral Surg Oral Med Oral Pathol Oral Radiol 113:695–703.  https://doi.org/10.1016/j.oooo.2011.11.011 CrossRefGoogle Scholar
  25. 25.
    Vermeer J, Renders G, van Duin MA, Jansen IDC, Bakker LF, Kroon SA, de Vries TJ, Everts V (2017) Bone-site-specific responses to zoledronic acid. Oral Dis 23:126–133.  https://doi.org/10.1111/odi.12587 CrossRefPubMedGoogle Scholar
  26. 26.
    Vermeer JA, Jansen ID, Marthi M et al (2013) Jaw bone marrow-derived osteoclast precursors internalize more bisphosphonate than long-bone marrow precursors. Bone. 57:242–251.  https://doi.org/10.1016/j.bone.2013.08.007 CrossRefPubMedGoogle Scholar
  27. 27.
    Koivukangas A, Tuukkanen J, Hannuniemi R, Jamsa T, Kippo K, Jalovaara P (2001) Effects of long-term administration of clodronate on growing rat bone. Calcif Tissue Int 69:350–355CrossRefGoogle Scholar
  28. 28.
    Koivukangas A, Tuukkanen J, Kippo K, Jämsä T, Hannuniemi R, Pasanen I, Väänänen K, Jalovaara P (2003) Long-term administration of clodronate does not prevent fracture healing in rats. Clin Orthop Relat Res 408:268–278CrossRefGoogle Scholar
  29. 29.
    Lepola VT, Hannuniemi R, Kippo K, Lauren L, Jalovaara P, Vaananen HK (1996) Long-term effects of clodronate on growing rat bone. Bone. 18:191–196CrossRefGoogle Scholar
  30. 30.
    Martelli SJR, Damian MF, Gomes APN, Schinestsck AR, Silva AER, Vasconcelos ACU (2017) Comparison of effects of zoledronic acid and clodronate on the bone structure: imaginological and histomorphometrical study in vivo. J Oral Pathol Med 46:632–636.  https://doi.org/10.1111/jop.12546 CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Stephanie Joana Roman Martelli
    • 1
  • Melissa Feres Damian
    • 1
  • André Ribeiro Schinestsck
    • 1
  • Lauren Frenzel Schuch
    • 2
  • Andreia Morales Cascaes
    • 1
  • Ana Carolina Uchoa Vasconcelos
    • 1
    • 3
    Email author
  1. 1.Graduate Program in DentistryUniversidade Federal de PelotasPelotasBrazil
  2. 2.Graduate Program in DentistryUniversidade Federal de Minas GeraisBelo HorizonteBrazil
  3. 3.Serviço de Patologia Bucal, Faculdade de OdontologiaUniversidade Federal de PelotasPelotasBrazil

Personalised recommendations