Turkiye Klinikleri Journal of Dental Sciences

.: ORIGINAL RESEARCH
Nitrojen İçeriği, Bifosfonata Bağlı Çene Kemiği Osteonekrozunun Nedeni mi? Fareler Üzerinde Deneysel Çalışma
Is Nitrogen Containing the Reason of Bisphosphonated Induced Osteonecrosis of Jaws? An Experimental Study on Rats
Sabit DEMİRCANa,b
aBeykent Üniversitesi Meslek Yüksekokulu, Ağız Sağlığı Bölümü, İstanbul, TÜRKİYE
bİstanbul Üniversitesi Diş Hekimliği Fakültesi, Ağız, Diş ve Çene Hastalıkları ve Cerrahisi ABD, İstanbul, TÜRKİYE
Turkiye Klinikleri J Dental Sci. 2020;26(2):153-8
doi: 10.5336/dentalsci.2019-66637
Article Language: TR
Full Text
ÖZET
 Amaç: Bifosfonatlar kemik rezorpsiyonu üzerine inhibe edici etkileri nedeni ile iskelet sistemiyle ilgili rahatsızlıklarda sıklıkla kullanılmaktadır. Bifosfonatların ciddi bir yan etkisi, bifosfonata bağlı gelişen çene kemiği osteonekrozudur. Bu yan etki çoğunlukla nitrojen içeren bisfofonatlar ile görülse de nitrojen içermeyen bifosfonatlarla bildirilen olgular vardır. Çalışmamızda, nitrojen içeren (NBP) ve içermeyen (non-NBPs) bifosfonat kullanımının sıçan çekim yarası ve yumuşak doku iyileşmesine etkilerinin histopatolojik olarak incelenmesini amaçladık. Gereç ve Yöntemler: Bu amaçla 48 adet Sprague-Dawley cinsi sıçan 3 gruba ayrılarak çalışma yapılmıştır. Birinci gruba nitrojen içeren bifosfonat (zoledronik asit), ikinci gruba ise nitrojen içermeyen bifosfonat (etidronik asit) 7, 14 ve 21. günlerde subkutan olarak enjekte edilmiştir. Üçüncü grup ise kontrol grubu olarak tayin edilmiştir. Dördüncü haftanın sonunda tüm sıçanların sağ birinci mandibular molar dişi çekilmiş, palatinal diş etinde 5 mm uzunluğunda, 1 mm derinliğinde kesi gerçekleştirilmiştir. Çalışmaya dâhil edilen tüm denekler 6 hafta sonunda sakrifiye edilmiş ve elde edilen örnekler histopatolojik incelemeye tabi tutulmuştur. Bulgular: Sonuçlarımız, NBP kullanımının çekim soketi ve çevresinde mikroorganizma kolonizasyonunu arttırdığını, osteoklast sayısını ve damarlanmayı baskıladığını, çekim soketi iyileşmesini geciktirdiğini göstermiştir. Çalışmamızda 6 hafta sonunda NBP ile açığa çıkmış nekroze kemik dokusu izlenmiş, ancak non-NBP ile açığa çıkmış kemik veya ülserasyon görülmemiştir. Sonuç: Bu sonuçlar, nitrojen içeren bifosfonatların içermeyenlere kıyasla daha yüksek oranda osteonekroz ve gecikmiş yara iyileşmesine neden olduklarını göstermektedir.

Anahtar Kelimeler: Çenelerin bisfofonat ilişkili osteonekrozu; yara iyileşmesi
ABSTRACT
 Objective: Bisphosphonates that inhibit bone resorption are frequently used to treat skeletal-related events. A severe adverse effect caused by such drugs is bisphosphonate related osteonecrosis of the jaws. Bisphosphonate related osteonecrosis of the jaws mostly reported with nitrogen containing bisphosphonates, but there is reports with non-nitrogen containing bisphosphonates induced osteonecrosis. In this study, our aim is to examine the effects of systemic use of both nitrogen containing (NBP) and non-nitrogen containing bisphosphonates (non-NBPs) on healing of rats extraction sockets and soft tissue wounds histo-pathologically. Material and Methods: Therefore 48 Sprague-Dawley rats are separated into 3 groups. Animals in Group 1 injected with a NBP (zoledronic acid) and animals in Group 2 injected with a non- NBP (etidronic acid) on day 7, 14 and 21. Group 3 assigned as a control group. After 28 days, palatinal gingiva incised 5 mm long, 1 mm depth and left mandibular first molar tooth of rats extracted. After 4 weeks of surgical operations all rats sacrificed and the obtained samples examined histo-pathologically. Results: Our results showed that systemic application of NBP increases the colonization of microorganisms on and near the extraction socket; inhibits vascularization, healing of extraction socket and decreases the amount of osteoclasts. In present study we observed that 6 exposed bone with NBP; however etidronate didn't caused exposed bone or ulceration. Conclusion: These results suggests NBPs have much risk for osteonecrosis and delayed wound healing than non-NBPs.

Keywords: Biphosphonate-associated osteonecrosis of jaw; wound healing
REFERENCES:
  1. Liberman UA, Weiss SR, Bröll J, Minne HW, Quan H, Bell NH, et al. Effect of oral alendronate on bone mineral density and the incidence of fractures in postmenopausal osteoporosis. The Alendronate Phase III Osteoporosis Treatment Study Group. N Engl J Med. 1995;333(22):1437-44. [Crossref]  [PubMed] 
  2. Ruggiero S, Dodson TB, Fantasia J, Goodday R, Aghaloo T, Mehrotra B, et al; American Association of Oral and Maxillofacial Surgeons. 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. [Crossref]  [PubMed] 
  3. Marx RE. Pamidronate (Aredia) and zoledronate (Zometa) induced avascular necrosis of the jaws: a growing epidemic. J Oral Maxillofac Surg. 2003;61:115-7. [Crossref] 
  4. Vescovi P, Campisi G, Fusco V, Mergoni G, Manfredi M, Merigo E, et al. Surgery-triggered and non surgery-triggered Bisphosphonate-related Osteonecrosis of the Jaws (BRONJ): A retrospective analysis of 567 cases in an Italian multicenter study. Oral Oncol. 2011;47(3):191-4. [Crossref]  [PubMed] 
  5. Ruggiero SL, Mehrotra B, Rosenberg TJ, Engroff SL. Osteonecrosis of the jaws associated with the use of bisphosphonates: a review of 63 cases. J Oral Maxillofac Surg. 2004;62(5): 527-34. [Crossref]  [PubMed] 
  6. Soundia A, Hadaya D, Esfandi N, Gkouveris I, Christensen R, Dry SM, et al. Zoledronate impairs socket healing after extraction of teeth with experimental periodontitis. J Dent Res. 2018;97(3):312-20. [Crossref]  [PubMed]  [PMC] 
  7. Mashiba T, Hirano T, Turner CH, Forwood MR, Johnston CC, Burr DB. Suppressed bone turnover by bisphosphonates increases microdamage accumulation and reduces some biomechanical properties in dog rib. J Bone Miner Res. 2000;15(4):613-20. [Crossref]  [PubMed] 
  8. Zaki AE, Vanhuysen G. Histology of the periodontium following tooth movement. J Dent Res. 1963;42:1373-9. [Crossref]  [PubMed] 
  9. Rygh P. Ultrastructural changes in pressure zones of human periodontium incident to orthodontic tooth movement. Acta Odontol Scand. 1973;31(2):109-22. [Crossref]  [PubMed] 
  10. Yamaguchi K, Oizumi T, Funayama H, Kawamura H, Sugawara S, Endo Y. Osteonecrosis of the jawbones in 2 osteoporosis patients treated with nitrogen-containing bisphosphonates: osteonecrosis reduction replacing NBP with non-NBP (etidronate) and rationale. J Oral Maxillofac Surg. 2010;68(4): 889-97. [Crossref]  [PubMed] 
  11. Tanaka Y, Nagai Y, Dohdoh M, Oizumi T, Ohki A, Kuroishi T, et al. In vitro cytotoxicity of zoledronate (nitrogen-containing bisphosphonate: NBP) and/or etidronate (non-NBP) in tumour cells and periodontal cells. Arch Oral Biol. 2013;58(6):628-37. [Crossref]  [PubMed] 
  12. Ali-Erdem M, Burak-Cankaya A, Cemil-Isler S, Demircan S, Soluk M, Kasapoglu C, et al. Extraction socket healing in rats treated with bisphosphonate: animal model for bisphosphonate related osteonecrosis of jaws in multiple myeloma patients. Med Oral Patol Oral Cir Bucal. 2011;16(7):879-83. [Crossref]  [PubMed] 
  13. Khan AA, Morrison A, Kendler DL, Rizzoli R, Hanley DA, Felsenberg D, et al.; International Task Force on Osteonecrosis of the Jaw. Case-Based Review of Osteonecrosis of the Jaw (ONJ) and Application of the International Recommendations for Management from the International Task Force on ONJ. J Clin Densitom. 2017;20(1):8-24. [Crossref]  [PubMed] 
  14. Pietrokovski J, Massler M. Ridge remodeling after tooth extrac¬tion in rats. J Dent Res. 1967;46(1):222-31. [Crossref] 
  15. Johansen JR. Repair of the post-extraction alveolus in the Wistar rat. A histologic and autoradiographic study. Acta Odontol Scand. 1970;28(4): 441-61. [Crossref]  [PubMed] 
  16. Mada EY, Santos AC, Fonseca AC, Biguetti CC, Neves FT, Saraiva PP, et al. Effects of green tea and bisphosphonate association on dental socket repair of rats. Arch Oral Biol. 2017;75:1-7. [Crossref]  [PubMed] 
  17. Silva PG, Ferreira Junior AE, Teófilo CR, Barbosa MC, Lima Júnior RC, Sousa FB, et al. Effect of different doses of zoledronic acid in establishing of bisphosphonate related osteonecrosis. Arch Oral Biol. 2015;60(9):1237-45. [Crossref]  [PubMed] 
  18. Barba-Recreo P, Del Castillo Pardo de Vera JL, García-Arranz M, Yébenes L, Burgue-o M. Zoledronic acid-related osteonecrosis of the jaws. Experimental model with dental extractions in rats. J Craniomaxillofac Surg. 2013;42(6):744-50. [Crossref]  [PubMed] 
  19. Williams DW, Lee C, Kim T, Yagita H, Wu H, Park S, et al. Impaired bone resorption and woven bone formation are associated with development of osteonecrosis of the jaw-like lesions by bisphosphonate and anti-receptor activator of NF-kB ligand antibody in mice. Am J Pathol. 2014;184(11):3084-93. [Crossref]  [PubMed]  [PMC] 
  20. Hikita H, Miyazawa K, Tabuchi M, Kimura M, Goto S. Bisphos¬phonate administration prior to tooth extraction delays initial healing of the extraction socket in rats. J Bone Miner Metab. 2009;27(6):663-72. [Crossref]  [PubMed] 
  21. Oizumi T, Funayama H, Yamaguchi K, Yokoyama M, Takahashi H, Yamamoto M, et al. Inhibition of necrotic actions of nitrogen-containing bisphosphonates (NBPs) and their elimination from bone by etidronate (a non-NBP): a proposal for possible utilization of etidronate as a substitution drug for NBPs. J Oral Maxillofac Surg. 2010;68(5):1043-54. [Crossref]  [PubMed] 
  22. Parfitt AM, Drezner MK, Glorieux FH, Kanis JA, Malluche H, Meunier PJ, et al. Bone histomorphometry: standardization of nomenclature, symbols and units. Reports of the ASBMR Histomorhphometry Nomenclature Committee. J Bone Miner Res. 1987;2(6):595-610. [Crossref]  [PubMed] 
  23. Weinstein RS, Roberson PK, Manolagas SC. Giant osteoclast formation and long-term oral bisphosphonate therapy. N Engl J Med. 2009;360(1):53-62. [Crossref]  [PubMed]  [PMC] 
  24. Pabst AM, Ziebart T, Ackermann M, Konerding MA, Walter C. Bisphosphonates' antiangiogenic potency in the development of bisphosphonate-associated osteonecrosis of the jaws: influence on microvessel sprouting in an in vivo 3D Matrigel assay. Clin Oral Investig. 2014;18(3):1015-22. [Crossref]  [PubMed] 
  25. Frith J, Mönkkönen J, Blackburn G, Russell R, Rogers M. Clodronate and liposome-encapsulated clodronate are metabolized to a toxic ATP analog, adenosine 5′-(beta, gamma-dichloromethylene) triphosphate, by mammalian cells in vitro. J Bone Miner Res. 1997;12(9):1358-67. [Crossref]  [PubMed] 
  26. van Beek ER, Cohen LH, Leroy IM, Ebetino FH, Löwik CW, Papapoulos SE. Differentiating the mechanisms of antiresorptive action of nitrogen containing bisphosphonates. Bone. 2003;33(5):805-11. [Crossref]  [PubMed] 
  27. Allam E, Allen M, Chu TM, Ghoneima A, Jack Windsor L. In vivo effects of zoledronic acid on oral mucosal epithelial cells. Oral Dis. 2011;17(3): 291-7. [Crossref]  [PubMed]  [PMC] 
  28. Sonis ST, Watkins BA, Lyng GD, Lerman MA, Anderson KC. Bony changes in the jaws of treated with zoledronic acid and dexamethasone before dental extractions mimic bisphosphonate-related osteonecrosis in cancer patients. Oral Oncol. 2009;45(2):164-72. [Crossref]  [PubMed] 

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