RATLARDA DENEYSEL OLARAK BİFOSFONATA BAĞLI ÇENE OSTEONEKROZU OLUŞTURULMASI

Abstract

Bifosfonat türevi ilaçlar, kemik metabolizması bozukluğu ile ilişkili birçok hastalıkta kullanılmaktadır. Bu ilaçların kullanımı sonrası gelişen ciddi yan etkilerden biri de bifosfonata bağlı çene osteonekrozudur. Bu çalışmada, ratlara bifosfonat uygulaması ve diş çekimi sonrası çene kemiklerinde osteonekroz oluşturulan hayvan modeli sunulmuştur. Çalışmamızda Wistar Albino ırkı 24 adet dişi rat 2 gruba ayrılmıştır. 1. gruptaki ratların (n=12) alt çene sol birinci ve ikinci molar dişleri çekildikten sonra alveol kemiğinde defekt oluşturulmuştur. 2. gruptaki ratlara (n=12) 0.1mg/kg zoledronat 8 hafta boyunca haftada 3 kez intraperitonel olarak uygulanmış ve bu sürenin sonunda ilk gruba uygulanan aynı cerrahi işlemler gerçekleştirilmiştir. Hayvanlar sakrifiye edilerek diş çekim bölgesi klinik, histolojik ve radyolojik olarak değerlendirilmiştir. Bu çalışmanın sonuçlarında, radyolojik açıdan 2. grubun defekt hacmi değeri ortalamasının 1. grubunkinden istatistiksel olarak anlamlı derecede daha geniş olduğu tespit edilmiştir. (p<0,05). 1. gruptaki hiçbir hayvanda klinik olarak nekrotik kemik oluşumu gözlenmemiştir. Ancak, 2. gruptaki deneklerin %45 ‘inde nekrotik kemik varlığı izlenmiştir. Sonuç olarak, ratlara zoledronik asitin uygulanması sonrası diş çekimi ile osteonekroz gelişen hayvan modeli oluşturulabilir

Keywords

• Bifosfonat, alveol defekti, osteonekroz.

Experimental Development of Bisphosphonate Induced Osteonecrosis of The Jaws in Rats

Abstract

Bisphosphonates are used for the treatment of diseases associated with bone metabolism disorders. One of the serious side effects due to the usage of this kind of drugs is the bisphosphonate related osteonecrosis of the jaws. In this study, we present an animal model in rats which were treated with bisphosphonate and developed osteonecrosis of jaw bones after dental extraction. 24 Wistar Albino female rats were divided randomly into 2 groups. In group 1 (n=12), mandibular left molars extraction and alveolar bone defects were established in the same region. In group 2 (n=12), 0.1mg/kg zoledronate, during a-8-week period for 3-times in a week was intraperitoneally injected, afterwards rats were underwent the same surgical procedure as in group 1. At the end of this period, animals were sacrificed for radiological, histological and clinical evaluations. As a result, the mean value of volume defects in group 2 was found significantly larger than the values of group 2 in radiologic aspect (p<0,05). Clinically, necrotic bone formation was not observed in any of the animals in group 1, whereas necrotic bone formation was observed in 45% of the animals in group 2. In conclusion, an animal model can be developed by administering zoledronic acid with dental extraction in rats.

Keywords

• Bisphosphonates, alveolar defect, osteonecrosis.

References

1. 1. Ertaş ET, Atıcı MY. Bifosfonatlar ve çene kemiğinde görülen osteonekroz. Selcuk Dental Journal 2016; 2 (2):91-100.
2. 2. Marx RE. Pamidronate (Aredia) and zoledronate (Zometa) induced avascular necrosis of the jaws: a growing epidemic. J Oral Maxillofac Surg 2003; 61 (9):1115-1117.
3. 3. Ruggiero SL, Dodson TB, Fantasia J, 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): 1938-1956.
4. 4. Reid IR, editor Anti-resorptive therapies for osteoporosis. Semin Cell Dev Biol 2008; 19(5):473- 478.
5. 5. Akarslan ZZ, Kahraman SA. Kemik metastazı yapmış prostat kanseri tedavisinde kullanılan bifosfonata bağlı olarak çene kemiklerinde gelişen osteonekroz: vaka raporu ve literatür derlemesi. Atatürk Üniv Diş Hek Fak Derg 2008; 18(3): 105-110.
6. 6. Şalvarcı A, Altınay S. Mandibular osteonecrosis due to bisphosphonate use. Turkish Journal of Urology 2015;41(1) 43-47.
7. 7. Keskinrüzgar A, Yanık S, Aras MH, Çetiner S. Teriparatid ve diş hekimliği. Acta Odontol Turca 2015; 32(13):165-170.
8. 8. Barba-Recreo P, García-Arranz M, Yébenes L, Burgueño M, Del Castillo Pardo De Vera JL. Zoledronic acid–related osteonecrosis of the jaws. Experimental model with dental extractions in rats. J Craniomaxillofac Surg 2014;42(6):744-750.

9. 9. Conte Neto N, Spolidorio LC, Andrade CR, et al. Experimental development of bisphosphonate related osteonecrosis of the jaws in rodents. Int J Exp Pathol 2013;94(1): 65-73.
10. 10. Biasotto M, Chiandussi S, Zacchigna S, et al. A novel animal model to study non- spontaneous bisphosphonates osteonecrosis of jaw. J Oral Pathol Med 2010;39(5):390-396.
11. 11. Maahs MP, Azambuja AA, Campos MM, Salum FG, Cherubini K. Association between bisphosphonates and jaw osteonecrosis: a study in Wistar rats. Head Neck. 2011; 33(2):199-207.
12. 12. Khosla S, Burr D, Cauley J, et al. Bisphosphonate associated osteonecrosis of the jaw: report of a task force of the American Society for Bone and Mineral Research. J Bone Miner Res 2007; 22(10):1479- 1491.
13. 13. Gibbs RA, Weinstock GM, Metzker ML, et al. Genome sequence of the Brown Norway rat yields insights into mammalian evolution. Nature 2004; 428 (6982):493-521.
14. 14. Sharma D, Hamlet S, Petcu E, Ivanovski S. Animal models for bisphosphonate related osteonecrosis of the jaws an appraisal. Oral Dis 2013; 19(8):747- 754.
15. 15. Li EC, Davis LE. Zoledronic acid: a new parenteral bisphosphonate. Clin Ther 2003; 25(11):2669- 2708.
16. 16. Uyanne J, Calhoun CC, Le AD. Antiresorptive Drug– Related Osteonecrosis of the Jaw. Dent Clin North Am 2014; 58(2):369-384.
17. 17. 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):1567-1575.
18. 18. Van den Wyngaert T, Huizing MT, Vermorken JB. Osteonecrosis of the jaw related to the use of bisphosphonates. Curr Opin Oncol 2007; 19(4):315 -322.
19. 19. Melo MD, Obeid G. Osteonecrosis of the jaws in patients with a history of receiving bisphosphonate therapy: strategies for prevention and early recognition. J Am Dent Assoc 2005; 136(12):1675- 1681.