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Investigation of the Effect of Pentoxifylline and Tocopherol on Osseous Healing Following Tooth Extraction in Bisphosphonate-Administered Rats

Year 2021, Volume: 2 Issue: 2, 98 - 106, 05.05.2021
https://doi.org/10.47482/acmr.2021.22

Abstract

Background: The incidence of medication-related osteonecrosis of the jaw has increased with the widespread use of bisphosphonates. Present study aimed to evaluate the effect of pentoxifylline and/or tocopherol alone or in combination, on bisphosphonate-induced osteonecrosis in tooth extracted rat jaw.

Methods: 24 rats were randomly assigned to 4 groups and each animal received intraperitoneal zoledronic acid injection 0.06 mg/ kg/week for 3 weeks. Following the zoledronic acid application, the lower right first molars of the rats were extracted on day 22. Starting from the day of tooth extraction animals received intraperitoneal pentoxifylline and/or tocopherol injections. Fourteen days later all rats were sacrificed. RANKL and osteoprotegerin (OPG) in blood were measured, and mandibles were examined histologically. When the inter-group differences were evaluated, the Kruskal Wallis-H Test and the Chi-square analysis were used.

Results: Each groups’ serum RANKL, OPG and RANKL/OPG levels did not reveal any statistically significant differences. There were no statistically significant differences in terms of bone necrosis, abscess formation, inflammation, osteoblastic/osteoclastic activity, bone cellularity and epithelial integrity.

Conclusions: Pentoxifylline and/or tocopherol injections alone or in combination did not have any statistically significant effect on the jaw following tooth extraction in bisphosphonate-induced rat animal model.

References

  • 1. Morishita K, Yamada SI, Kawakita A, Hashidume M, Tachibana A, Takeuchi N, et al. Treatment outcomes of adjunctive teriparatide therapy for medication-related osteonecrosis of the jaw (MRONJ): A multicenter retrospective analysis in Japan. J Orthop Sci. 2020;25(6):1079-1083.
  • 2. 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(10):1938-56.
  • 3. Marx RE. Pamidronate (Aredia) and zoledronate (Zometa) induced avascular necrosis of the jaws: a growing epidemic. J Oral Maxillofac Surg. 2003;61(9):1115-7.
  • 4. Voss PJ, Poxleitner P, Schmelzeisen R, Stricker A, Semper-Hogg W. Update MRONJ and perspectives of its treatment. J Stomatol Oral Maxillofac Surg. 2017;118(4):232-235.
  • 5. Nicolatou-Galitis O, Schiodt M, Mendes RA, Ripamonti C, Hope S, Drudge-Coates L, et al. Medication-related osteonecrosis of the jaw: definition and best practice for prevention, diagnosis, and treatment. Oral Surg Oral Med Oral Pathol Oral Radiol. 2019;127(2):117-135.
  • 6. Hirshberg A, Lib M, Kozlovsky A, Kaplan I. The influence of inflammation on the polarization colors of collagen fibers in the wall of odontogenic keratocyst. Oral Oncol. 2007;43(3):278-82.
  • 7. Kalra S, Jain V. Dental complications and management of patients on bisphosphonate therapy: A review article. J Oral Biol Craniofac Res. 2013;3(1):25-30.
  • 8. Holtmann H, Lommen J, Kubler NR, Sproll C, Rana M, Karschuck P, et al. Pathogenesis of medication-related osteonecrosis of the jaw: a comparative study of in vivo and in vitro trials. J Int Med Res. 2018;46(10):4277-4296.
  • 9. Voss P, Poxleitner P, Schmelzeisen R, Stricker A, Semper-Hogg W. Update MRONJ and perspectives of its treatment. J Stomatol Oral Maxillofac Surg. 2017;118(4):232-235.
  • 10. Senel FC, Kadioglu Duman M, Muci E, Cankaya M, Pampu AA, Ersoz S, et al. Jaw bone changes in rats after treatment with zoledronate and pamidronate. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2010;109(3):385-91.
  • 11. Barba-Recreo P, Del Castillo Pardo de Vera JL, Garcia-Arranz M, Yebenes L, Burgueno M. Zoledronic acid - related osteonecrosis of the jaws. Experimental model with dental extractions in rats. J Craniomaxillofac Surg. 2014;42(6):744-50.
  • 12. Marino KL, Zakhary I, Abdelsayed RA, Carter JA, O’Neill JC, Khashaba RM, et al. Development of a rat model of bisphosphonaterelated osteonecrosis of the jaw (BRONJ). J Oral Implantol. 2012;38 Spec No:511-8.
  • 13. Marx RE, Sawatari Y, Fortin M, Broumand V. Bisphosphonate-induced exposed bone (osteonecrosis/osteopetrosis) of the jaws: risk factors, recognition, prevention, and treatment. J Oral Maxillofac Surg. 2005;63(11):1567-75.
  • 14. Takami M, Cho ES, Lee SY, Kamijo R, Yim M. Phosphodiesterase inhibitors stimulate osteoclast formation via TRANCE/RANKL expression in osteoblasts: possible involvement of ERK and p38MAPK pathways. FEBS Lett. 2005;579(3):832-8.
  • 15. Horiuchi H, Saito N, Kinoshita T, Wakabayashi S, Tsutsumimoto T, Otsuru S, et al. Enhancement of recombinant human bone morphogenetic protein-2 (rhBMP-2)-induced new bone formation by concurrent treatment with parathyroid hormone and a phosphodiesterase inhibitor, pentoxifylline. J Bone Miner Metab. 2004;22(4):329-34.
  • 16. Aydin K, Sahin V, Gursu S, Mercan AS, Demir B, Yildirim T. Effect of pentoxifylline on fracture healing: an experimental study. Eklem Hastalik Cerrahisi. 2011;22(3):160-5.
  • 17. Sen CK, Khanna S, Roy S. Tocotrienols: Vitamin E beyond tocopherols. Life Sci. 2006;78(18):2088-98.
  • 18. Turk C, Halici M, Guney A, Akgun H, Sahin V, Muhtaroglu S. Promotion of fracture healing by vitamin E in rats. J Int Med Res. 2004;32(5):507-12.
  • 19. Bohn JC, Schussel JL, Stramandinoli-Zanicotti RT, Sassi LM. Tissue repair in osteoradionecrosis using pentoxifylline and tocopherol-- report of three cases. Oral Maxillofac Surg. 2016;20(1):97-101.
  • 20. Magremanne M, Reychler H. Pentoxifylline and tocopherol in the treatment of yearly zoledronic acid-related osteonecrosis of the jaw in a corticosteroid-induced osteoporosis. J Oral Maxillofac Surg. 2014;72(2):334-7.
  • 21. Blair JM, Zheng Y, Dunstan CR. RANK ligand. Int J Biochem Cell Biol. 2007;39(6):1077-81.22. Wang F, Chen W, Chen H, Mo L, Jin H, Yu Z, et al. Comparison between zoledronic acid and clodronate in the treatment of prostate cancer patients with bone metastases. Med Oncol. 2013;30(3):657.
  • 23. Huja SS, Fernandez SA, Phillips C, Li Y. Zoledronic acid decreases bone formation without causing osteocyte death in mice. Arch Oral Biol. 2009;54(9):851-6.
  • 24. Yang H, Pan H, Yu F, Chen K, Shang G, Xu Y. A novel model of bisphosphonate-related osteonecrosis of the jaw in rats. Int J Clin Exp Pathol. 2015;8(5):5161-7.
  • 25. Mercatali L, Ricci M, Scarpi E, Serra P, Fabbri F, Ricci R, et al. RANK/ RANK-L/OPG in patients with bone metastases treated with anticancer agents and zoledronic acid: a prospective study. Int J Mol Sci. 2013;14(6):10683-93.
Year 2021, Volume: 2 Issue: 2, 98 - 106, 05.05.2021
https://doi.org/10.47482/acmr.2021.22

Abstract

References

  • 1. Morishita K, Yamada SI, Kawakita A, Hashidume M, Tachibana A, Takeuchi N, et al. Treatment outcomes of adjunctive teriparatide therapy for medication-related osteonecrosis of the jaw (MRONJ): A multicenter retrospective analysis in Japan. J Orthop Sci. 2020;25(6):1079-1083.
  • 2. 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(10):1938-56.
  • 3. Marx RE. Pamidronate (Aredia) and zoledronate (Zometa) induced avascular necrosis of the jaws: a growing epidemic. J Oral Maxillofac Surg. 2003;61(9):1115-7.
  • 4. Voss PJ, Poxleitner P, Schmelzeisen R, Stricker A, Semper-Hogg W. Update MRONJ and perspectives of its treatment. J Stomatol Oral Maxillofac Surg. 2017;118(4):232-235.
  • 5. Nicolatou-Galitis O, Schiodt M, Mendes RA, Ripamonti C, Hope S, Drudge-Coates L, et al. Medication-related osteonecrosis of the jaw: definition and best practice for prevention, diagnosis, and treatment. Oral Surg Oral Med Oral Pathol Oral Radiol. 2019;127(2):117-135.
  • 6. Hirshberg A, Lib M, Kozlovsky A, Kaplan I. The influence of inflammation on the polarization colors of collagen fibers in the wall of odontogenic keratocyst. Oral Oncol. 2007;43(3):278-82.
  • 7. Kalra S, Jain V. Dental complications and management of patients on bisphosphonate therapy: A review article. J Oral Biol Craniofac Res. 2013;3(1):25-30.
  • 8. Holtmann H, Lommen J, Kubler NR, Sproll C, Rana M, Karschuck P, et al. Pathogenesis of medication-related osteonecrosis of the jaw: a comparative study of in vivo and in vitro trials. J Int Med Res. 2018;46(10):4277-4296.
  • 9. Voss P, Poxleitner P, Schmelzeisen R, Stricker A, Semper-Hogg W. Update MRONJ and perspectives of its treatment. J Stomatol Oral Maxillofac Surg. 2017;118(4):232-235.
  • 10. Senel FC, Kadioglu Duman M, Muci E, Cankaya M, Pampu AA, Ersoz S, et al. Jaw bone changes in rats after treatment with zoledronate and pamidronate. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2010;109(3):385-91.
  • 11. Barba-Recreo P, Del Castillo Pardo de Vera JL, Garcia-Arranz M, Yebenes L, Burgueno M. Zoledronic acid - related osteonecrosis of the jaws. Experimental model with dental extractions in rats. J Craniomaxillofac Surg. 2014;42(6):744-50.
  • 12. Marino KL, Zakhary I, Abdelsayed RA, Carter JA, O’Neill JC, Khashaba RM, et al. Development of a rat model of bisphosphonaterelated osteonecrosis of the jaw (BRONJ). J Oral Implantol. 2012;38 Spec No:511-8.
  • 13. Marx RE, Sawatari Y, Fortin M, Broumand V. Bisphosphonate-induced exposed bone (osteonecrosis/osteopetrosis) of the jaws: risk factors, recognition, prevention, and treatment. J Oral Maxillofac Surg. 2005;63(11):1567-75.
  • 14. Takami M, Cho ES, Lee SY, Kamijo R, Yim M. Phosphodiesterase inhibitors stimulate osteoclast formation via TRANCE/RANKL expression in osteoblasts: possible involvement of ERK and p38MAPK pathways. FEBS Lett. 2005;579(3):832-8.
  • 15. Horiuchi H, Saito N, Kinoshita T, Wakabayashi S, Tsutsumimoto T, Otsuru S, et al. Enhancement of recombinant human bone morphogenetic protein-2 (rhBMP-2)-induced new bone formation by concurrent treatment with parathyroid hormone and a phosphodiesterase inhibitor, pentoxifylline. J Bone Miner Metab. 2004;22(4):329-34.
  • 16. Aydin K, Sahin V, Gursu S, Mercan AS, Demir B, Yildirim T. Effect of pentoxifylline on fracture healing: an experimental study. Eklem Hastalik Cerrahisi. 2011;22(3):160-5.
  • 17. Sen CK, Khanna S, Roy S. Tocotrienols: Vitamin E beyond tocopherols. Life Sci. 2006;78(18):2088-98.
  • 18. Turk C, Halici M, Guney A, Akgun H, Sahin V, Muhtaroglu S. Promotion of fracture healing by vitamin E in rats. J Int Med Res. 2004;32(5):507-12.
  • 19. Bohn JC, Schussel JL, Stramandinoli-Zanicotti RT, Sassi LM. Tissue repair in osteoradionecrosis using pentoxifylline and tocopherol-- report of three cases. Oral Maxillofac Surg. 2016;20(1):97-101.
  • 20. Magremanne M, Reychler H. Pentoxifylline and tocopherol in the treatment of yearly zoledronic acid-related osteonecrosis of the jaw in a corticosteroid-induced osteoporosis. J Oral Maxillofac Surg. 2014;72(2):334-7.
  • 21. Blair JM, Zheng Y, Dunstan CR. RANK ligand. Int J Biochem Cell Biol. 2007;39(6):1077-81.22. Wang F, Chen W, Chen H, Mo L, Jin H, Yu Z, et al. Comparison between zoledronic acid and clodronate in the treatment of prostate cancer patients with bone metastases. Med Oncol. 2013;30(3):657.
  • 23. Huja SS, Fernandez SA, Phillips C, Li Y. Zoledronic acid decreases bone formation without causing osteocyte death in mice. Arch Oral Biol. 2009;54(9):851-6.
  • 24. Yang H, Pan H, Yu F, Chen K, Shang G, Xu Y. A novel model of bisphosphonate-related osteonecrosis of the jaw in rats. Int J Clin Exp Pathol. 2015;8(5):5161-7.
  • 25. Mercatali L, Ricci M, Scarpi E, Serra P, Fabbri F, Ricci R, et al. RANK/ RANK-L/OPG in patients with bone metastases treated with anticancer agents and zoledronic acid: a prospective study. Int J Mol Sci. 2013;14(6):10683-93.
There are 24 citations in total.

Details

Primary Language English
Subjects Clinical Sciences
Journal Section ORIGINAL ARTICLE
Authors

Ezgi Tuncay 0000-0003-0387-956X

Mustafa Öztürk 0000-0003-3269-8880

Ayşenur Nergiz Tanıdır 0000-0002-9097-8904

Burcu Sengüven Toközlü 0000-0003-1507-4662

Özge Paşaoğlu 0000-0002-5221-9034

Publication Date May 5, 2021
Submission Date January 14, 2021
Published in Issue Year 2021 Volume: 2 Issue: 2

Cite

APA Tuncay, E., Öztürk, M., Tanıdır, A. N., Sengüven Toközlü, B., et al. (2021). Investigation of the Effect of Pentoxifylline and Tocopherol on Osseous Healing Following Tooth Extraction in Bisphosphonate-Administered Rats. Archives of Current Medical Research, 2(2), 98-106. https://doi.org/10.47482/acmr.2021.22

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