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

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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.

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References

  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

    Article  Google Scholar 

  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

    Article  CAS  PubMed  Google Scholar 

  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

    Article  CAS  PubMed  Google Scholar 

  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

    Article  CAS  PubMed  Google Scholar 

  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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Fleisher K, Kontio R, Otto S (2016) Antiresorptive drug-related osteonecrosis of the jaw (ARONJ) – a guide to research, 1st edn. AOCMF

  7. Russell RG (2007) Bisphosphonates: mode of action and pharmacology. Pediatrics 119:S150–S162

    Article  Google Scholar 

  8. Marx RE (2003) Pamidronate (Aredia) and zoledronate (Zometa) induced avascular necrosis of the jaws: a growing epidemic. J Oral Maxillofac Surg 61:1115–1117

    Article  Google Scholar 

  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

    Article  PubMed  Google Scholar 

  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

    Article  CAS  PubMed  Google Scholar 

  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

    Article  PubMed  Google Scholar 

  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

    Article  PubMed  Google Scholar 

  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

    Article  Google Scholar 

  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

    Article  PubMed  Google Scholar 

  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 8:667–672

    Article  Google Scholar 

  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

    Article  PubMed  Google Scholar 

  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

    Article  PubMed  Google Scholar 

  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

    Article  CAS  Google Scholar 

  19. Macerata R (2002) Zometa (zoledronic acid)—intravenous formulation. Investigator’s brochure for consultation. 8th ed.

  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 50:600–613

    CAS  PubMed  PubMed Central  Google Scholar 

  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 50:16–19

    Google Scholar 

  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

    Article  PubMed  Google Scholar 

  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

    Article  PubMed  Google Scholar 

  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

    Article  Google Scholar 

  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

    Article  PubMed  Google Scholar 

  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

    Article  CAS  PubMed  Google Scholar 

  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 69:350–355

    Article  CAS  Google Scholar 

  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 408:268–278

    Article  Google Scholar 

  29. Lepola VT, Hannuniemi R, Kippo K, Lauren L, Jalovaara P, Vaananen HK (1996) Long-term effects of clodronate on growing rat bone. Bone. 18:191–196

    Article  CAS  Google Scholar 

  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

    Article  CAS  PubMed  Google Scholar 

Download references

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.

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Correspondence to Ana Carolina Uchoa Vasconcelos.

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Martelli, S.J.R., Damian, M.F., Schinestsck, A.R. et al. Imaging and histomorphometric evaluation of mandible and tibia of rats treated with bisphosphonates. Oral Maxillofac Surg 23, 473–479 (2019). https://doi.org/10.1007/s10006-019-00807-9

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