Journal of Periodontal and Implant Science

Korean Academy of Periodontology (대한치주과학회)
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The effects of zoledronic acid on the progression of experimental periodontitis in rats: histological and microtomographic analyses

  • de Marcelos, Priscylla Goncalves Correia Leite (Universidade Federal de Alagoas School of Dentistry) ;
  • da Cruz Perez, Danyel Elias (Department of Clinical and Preventive Dentistry, Oral Pathology and Oral Radiology Sections, Universidade Federal de Pernambuco School of Dentistry) ;
  • Soares, Diego Moura (Department of Clinical and Preventive Dentistry, Oral Pathology and Oral Radiology Sections, Universidade Federal de Pernambuco School of Dentistry) ;
  • de Araujo, Samuel Silva (Department of Clinical and Preventive Dentistry, Oral Pathology and Oral Radiology Sections, Universidade Federal de Pernambuco School of Dentistry) ;
  • Evencio, Liriane Baratella (Department of Histology, Universidade Federal de Pernambuco) ;
  • Pontual, Maria Luiza dos Anjos (Department of Clinical and Preventive Dentistry, Oral Pathology and Oral Radiology Sections, Universidade Federal de Pernambuco School of Dentistry) ;
  • Ramos-Perez, Flavia Maria de Moraes (Department of Clinical and Preventive Dentistry, Oral Pathology and Oral Radiology Sections, Universidade Federal de Pernambuco School of Dentistry)
  • Received : 2020.02.12
  • Accepted : 2021.04.12
  • Published : 2021.08.30
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Abstract

Purpose: Periodontitis is considered a local risk factor for medication-related osteonecrosis of the jaws (MRONJ). However, little is known about the progression of periodontitis in the presence of zoledronic acid (ZOL). The aim of this study was to evaluate the effects of the systemic use of ZOL on the progression of experimental periodontitis (EP) in rats, as ZOL could modulate the progression of periodontitis and concomitantly cause MRONJ in individuals with periodontitis. Methods: Forty-eight male Wistar rats were randomly distributed in 6 groups (n=8 each). To induce EP, ligatures were placed around the right first mandibular molars. Three groups were treated with ZOL (0.15 mg/kg/week, intraperitoneal), and 3 with 0.9% saline solution (controls). In the ZOL/Lig30 and ZOL/Lig 15 groups, after 4 weeks of treatment with ZOL, EP was induced and euthanasia was performed after 30 and 15 days of EP induction, respectively. In both groups, the animals continued to receive ZOL after EP until the end of the experiment. In the Lig/ZOL group, EP was induced first, and 15 days later, ZOL was administered for 8 weeks, with euthanasia 1 week after the last dose. After euthanasia, the mandibles were evaluated using micro-computed microtomography (micro-CT) and histomorphometry. Bone loss was measured, and the presence of osteonecrosis was evaluated histologically. The data were evaluated using the Student t-test and the Mann-Whitney test, with a significance level of 5%. Results: In the Lig/ZOL group, micro-CT revealed less alveolar bone resorption in the distal root (P<0.01) than in the control group (Lig/Con). Histomorphometric analysis confirmed less alveolar bone resorption in the Lig/ZOL group (P=0.001). Histologically, osteonecrosis was more common in the ZOL groups. Conclusion: ZOL decreased alveolar bone resorption in rats with EP. However, it presented a higher risk for MRONJ.

Keywords

Acknowledgement

This study was supported in part by Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES), Finance code 001, and Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq), Brazil. The authors also thank the Computed Tomography Laboratory (LTC) of the Nucleus in Non-Destructive Testing of X-Ray Applications (NENDARX) of the Department of Nuclear Energy, Universidade Federal de Pernambuco, for technical support in obtaining the microtomographic images.

References

  1. Yarom N, Shapiro CL, Peterson DE, Van Poznak CH, Bohlke K, Ruggiero SL, et al. Medication-related osteonecrosis of the jaw: MASCC/ISOO/ASCO clinical practice guideline. J Clin Oncol 2019;37:2270-90. https://doi.org/10.1200/JCO.19.01186
  2. Aghaloo T, Hazboun R, Tetradis S. Pathophysiology of osteonecrosis of the jaws. Oral Maxillofac Surg Clin North Am 2015;27:489-96. https://doi.org/10.1016/j.coms.2015.06.001
  3. Ruggiero SL, Dodson TB, Fantasia J, Goodday R, Aghaloo T, Mehrotra B, et al. American Association of Oral and Maxillofacial Surgeons position paper on medication-related osteonecrosis of the jaw--2014 update. J Oral Maxillofac Surg 2014;72:1938-56. https://doi.org/10.1016/j.joms.2014.04.031
  4. Kang B, Cheong S, Chaichanasakul T, Bezouglaia O, Atti E, Dry SM, et al. Periapical disease and bisphosphonates induce osteonecrosis of the jaws in mice. J Bone Miner Res 2013;28:1631-40. https://doi.org/10.1002/jbmr.1894
  5. Aghaloo TL, Kang B, Sung EC, Shoff M, Ronconi M, Gotcher JE, et al. Periodontal disease and bisphosphonates induce osteonecrosis of the jaws in the rat. J Bone Miner Res 2011;26:1871-82. https://doi.org/10.1002/jbmr.379
  6. Cekici A, Kantarci A, Hasturk H, Van Dyke TE. Inflammatory and immune pathways in the pathogenesis of periodontal disease. Periodontol 2000 2014;64:57-80. https://doi.org/10.1111/prd.12002
  7. Giannobile WV. Host-response therapeutics for periodontal diseases. J Periodontol 2008;79:1592-600. https://doi.org/10.1902/jop.2008.080174
  8. Akram Z, Abduljabbar T, Kellesarian SV, Abu Hassan MI, Javed F, Vohra F. Efficacy of bisphosphonate as an adjunct to nonsurgical periodontal therapy in the management of periodontal disease: a systematic review. Br J Clin Pharmacol 2017;83:444-54. https://doi.org/10.1111/bcp.13147
  9. De Almeida J, Ervolino E, Bonfietti LH, Novaes VC, Theodoro LH, Fernandes LA, et al. Adjuvant therapy with sodium alendronate for the treatment of experimental periodontitis in rats. J Periodontol 2015;86:1166-75. https://doi.org/10.1902/jop.2015.150166
  10. Kanoriya D, Pradeep AR, Singhal S, Garg V, Guruprasad CN. Synergistic approach using platelet-rich fibrin and 1% alendronate for intrabony defect treatment in chronic periodontitis: a randomized clinical trial. J Periodontol 2016;87:1427-35. https://doi.org/10.1902/jop.2016.150698
  11. Duarte PM, de Vasconcelos Gurgel BC, Sallum AW, Filho GR, Sallum EA, Nociti FH Jr. Alendronate therapy may be effective in the prevention of bone loss around titanium implants inserted in estrogendeficient rats. J Periodontol 2005;76:107-14. https://doi.org/10.1902/jop.2005.76.1.107
  12. Doku HC, Shklar G, Bugbee B. The effect of epsilon aminocaproic acid on the healing of extraction wounds in hamsters. Oral Surg Oral Med Oral Pathol 1966;22:569-77. https://doi.org/10.1016/0030-4220(66)90159-9
  13. Soares DM, Ramos-Perez F, Araujo SS, Correia Leite de Marcelos PG, Pontual AA, Perez D. Sildenafil citrate on experimental periodontitis in rats: microtomographic and histological analyses. Oral Dis 2018;24:1073-82. https://doi.org/10.1111/odi.12846
  14. Silva PG, Ferreira Junior AE, Teofilo CR, Barbosa MC, Lima Junior RC, Sousa FB, et al. Effect of different doses of zoledronic acid in establishing of bisphosphonate-related osteonecrosis. Arch Oral Biol 2015;60:1237-45. https://doi.org/10.1016/j.archoralbio.2015.05.015
  15. Yamamoto-Silva FP, Bradaschia-Correa V, Lima LA, Arana-Chavez VE. Ultrastructural and immunohistochemical study of early repair of alveolar sockets after the extraction of molars from alendronate-treated rats. Microsc Res Tech 2013;76:633-40. https://doi.org/10.1002/jemt.22210
  16. Li CL, Lu WW, Seneviratne CJ, Leung WK, Zwahlen RA, Zheng LW. Role of periodontal disease in bisphosphonate-related osteonecrosis of the jaws in ovariectomized rats. Clin Oral Implants Res 2016;27:1-6.
  17. McClung MR. Bisphosphonate therapy: how long is long enough? Osteoporos Int 2015;26:1455-7. https://doi.org/10.1007/s00198-014-3019-4
  18. Dannemann C, Zwahlen R, Gratz KW. Clinical experiences with bisphopsphonate induced osteochemonecrosis of the jaws. Swiss Med Wkly 2006;136:504-9.
  19. Viereck V, Emons G, Lauck V, Frosch KH, Blaschke S, Grundker C, et al. Bisphosphonates pamidronate and zoledronic acid stimulate osteoprotegerin production by primary human osteoblasts. Biochem Biophys Res Commun 2002;291:680-6. https://doi.org/10.1006/bbrc.2002.6510
  20. Moreira MM, Bradaschia-Correa V, Marques ND, Ferreira LB, Arana-Chavez VE. Ultrastructural and immunohistochemical study of the effect of sodium alendronate in the progression of experimental periodontitis in rats. Microsc Res Tech 2014;77:902-9. https://doi.org/10.1002/jemt.22413
  21. Franca TRT, Ramos-Perez FMM, Pontual ADA, Castro JFL, Bonan PRF, Perez DEDC. Effects of zoledronic acid in experimental periapical lesions in rats: an imaging and histological analysis. Braz Dent J 2017;28:566-72. https://doi.org/10.1590/0103-6440201601558
  22. Bonnet N, Lesclous P, Saffar JL, Ferrari S. Zoledronate effects on systemic and jaw osteopenias in ovariectomized periostin-deficient mice. PLoS One 2013;8:e58726. https://doi.org/10.1371/journal.pone.0058726
  23. Messer JG, Mendieta Calle JL, Jiron JM, Castillo EJ, Van Poznak C, Bhattacharyya N, et al. Zoledronic acid increases the prevalence of medication-related osteonecrosis of the jaw in a dose dependent manner in rice rats (Oryzomys palustris) with localized periodontitis. Bone 2018;108:79-88. https://doi.org/10.1016/j.bone.2017.12.025
  24. Yamashita J, Koi K, Yang DY, McCauley LK. Effect of zoledronate on oral wound healing in rats. Clin Cancer Res 2011;17:1405-14. https://doi.org/10.1158/1078-0432.CCR-10-1614