Cihan TOPAN, Erdem KILIÇ, Eser KILIÇ, Saim ÖZDAMAR, Emin KAYMAK

Teriparatidin ilaçlarla ilişkili çene osteonekrozu tedavisindeki etkinliği: hayvan çalışması

Amaç: Bu çalışmanın amacı, bifosfanat uygulamasını takiben diş çekimi sonrasında çene kemiklerinde oluşan osteonekrozun tedavisinde teriparatidin etkinliğinin deneysel olarak araştırılmasıdır. Gereç ve Yöntemler: Wistar Albino ırkı 48 adet dişi rat rastgele 4 gruba ayrıldı: I-Kontrol grubu; II-Zoledronik asit (ZA); III-ZA ve teriparatid; IV-ZA ve antibiyotik. Osteonekroz oluşturmak için kontrol grubu dışındaki tüm gruplara 8 hafta boyunca zoledronik asit enjekte edildi. ZA enjeksiyonlarından bir hafta sonra tüm hayvanların alt çene sol azı dişleri çekildi ve çekim soketlerinde kemik defekti oluşturuldu. Bu işlemden sonra üçüncü gruptaki ratlara 2 ay boyunca subkutan olarak teriparatid, dördüncü gruptaki ratlara 2 hafta boyunca intraperitoneal antibiyotik enjekte edildi. Hayvanlar radyolojik, histolojik, biyokimyasal ve klinik değerlendirmeler için sakrifiye edildi.Bulgular: Teriparatid uygulamasının biyokimyasal ve radyolojik açıdan kemik iyileşmesine istatistiksel olarak anlamlı bir etkisinin olmadığı tespit edilmiştir (p>0,05). Teriparatidin, osteonekroz geliştikten sonra klinik olarak iyileşmeye tam anlamıyla olumlu etkisinin olmadığı ama oluşan osteonekroz tablosunun daha da ilerlemesini engellediği gözlenmiştir. Ayrıca, ilacın histolojik olarak yumuşak doku ve kemik dokusu iyileşmesinde olumlu etkilerinin olduğu tespit edilmiştir. Sonuç: Bifosfanat uygulamasını takiben diş çekimi işleminin osteonekroz gelişimine sebep olduğu gözlenmiştir. Ayrca, teriparatid uygulamasının bu lezyonların tedavisinde kısmen olumlu etkileri olduğu tespit edilmiştir. Bu tedavinin optimum doz ve süresinin belirlenmesi için geniş grupları içeren ileri deneysel ve klinik çalışmalara ihtiyaç vardır. Anahtar Kelimeler: Bifosfonat, osteonekroz, teriparatid

Anahtar Kelimeler:

Bifosfonat, osteonekroz, teriparatid

Teriparatide’s potential role in the treatment of medication-related osteonecrosis of the jaw: an animal study.

Background: We aimed to investigate the efficacy of teriparatide experimentally on rats after the development of osteonecrosis with bisphosphonate usage.Methods: Rats were divided randomly into four groups: I-Control group; II-Zoledronic acid (ZA); III-ZA and teriparatide; IV-ZA and antibiotic. Osteonecrosis was generated by injecting zoledronic acid to all groups except control group for 8 weeks. A week after ZA injections, mandibular left molar extraction was performed and bone defect were created in the same regions of all animals. Afterwards, teriparatide was subcutaneously injected to rats in the third group; antibiotic was intraperitoneally injected to rats in the fourth group. Animals were sacrificed for the radiological, histological, biochemical and clinical evaluations.Results: Teriparatide therapy has not a statistically significant effect on radiological and biochemical aspects of bone healing (p>0.05). Teriparatide has not a positive effect clinically on bone healing after the development of osteonecrosis. However, application of this drug prevents further deterioration of osteonecrosis period clinically. Moreover, teriparatide has positive effects on soft tissue and bone healing histologically. Conclusions: Bisphosphonate uptake that followed by tooth extraction has been identified to induce the development of osteonecrosis. On the other hand teriparatide therapy has partially positive effects in the treatment of these lesions. However, further experimental and clinical studies including large groups are required for the determination optimum dose and duration of this treatment modality. Keywords: Bisphosphonate, osteonecrosis, teriparatide

Keywords:

Bisphosphonate, osteonecrosis, teriparatide,

PDF

___

Referanslar
1. Soydan S, Veziroğlu Şenel F, Araz K. Pathogenesis and Treatment of Bisphosphonate Induced Osteonecrosis of the Jaws. Clin Dent Res 2009;33:61-8.
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;72:1938-56.
3. Dayisoylu E, Şenel F, Üngör C, Tosun E, Çankaya M, Ersöz S, et al. The effects of adjunctive parathyroid hormone injection on bisphosphonate-related osteonecrosis of the jaws: an animal study. Int J Oral Maxillofac Surg 2013;42:1475-80.
4. Kakehashi H, Ando T, Minamizato T, Nakatani Y, Kawasaki T, Ikeda H, et al. Administration of teriparatide improves the symptoms of advanced bisphosphonate-related osteonecrosis of the jaw: preliminary findings. Int J Oral Maxillofac Surg 2015;44:1558-64.
5. Shen V, Dempster D, Mellish R, Birchman WE, Horbert W, Lindsay R. Effects of combined and separate intermittent administration of low-dose human parathyroid hormone fragment (1–34) and 17β-estradiol on bone histomorphometry in ovariectomized rats with established osteopenia. Calcif Tissue Int 1992;50:214-20.
6. Jiang Y, Zhao JJ, Mitlak BH, Wang O, Genant HK, Eriksen EF. Recombinant human parathyroid hormone (1–34)[teriparatide] improves both cortical and cancellous bone structure. J Bone Miner Res 2003;18:1932-41.
7. Harper RP, Fung E. Resolution of bisphosphonate-associated osteonecrosis of the mandible: possible application for intermittent low-dose parathyroid hormone [rhPTH (1-34)]. J Oral Maxillofacial Surg 2007;65:573-80.
8. Yao M, Shimo T, Ono Y, Obata K, Yoshioka N, Sasaki A. Successful treatment of osteonecrosis-induced fractured mandible with teriparatide therapy: A case report. Int J Surg Case Rep 2016;21:151-53.
9. Barba-Recreo P, García-Arranz M, Yébenes L, Burgueno M. Zoledronic acid–related osteonecrosis of the jaws. Experimental model with dental extractions in rats. J Craniomaxillofac Surg 2014;42:744-50.
10. Biasotto M, Chiandussi S, Zacchigna S, Moimas S, Dore F, Pozatto G, et al. A novel animal model to study non‐spontaneous bisphosphonates osteonecrosis of jaw. J Oral Pathol Med 2010;39:390-96.
11. Keskinruzgar A, Bozdag Z, Aras MH, Demir T, Yolcu U, Cetiner S. Histopathological effects of teriparatide in medication-related osteonecrosis of the jaw: an animal study. J Oral Maxillofac Surg 2016;74:68-78.
12. Lee JJ, Cheng SJ, Jeng JH, Chiang CP, Lau HP, Kok SH. Successful treatment of advanced bisphosphonate‐related osteonecrosis of the mandible with adjunctive teriparatide therapy. Head Neck 2011;33:1366-71.
13. Subramanian G, Cohen HV, Quek SY. A model for the pathogenesis of bisphosphonate-associated osteonecrosis of the jaw and teriparatide's potential role in its resolution. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2011;112:744-53.
14. Khan AA, Morrison A, Hanley DA, Felsenberg D, McCauley LK, O’Ryan F, et al. Diagnosis and management of osteonecrosis of the jaw: a systematic review and international consensus. J Bone Miner Res 2015;30:3-23.
15. Agaçayak K, Yuksel H, Atilgan S, Koparal M, Uçan MC, Özgöz M, et al. Experimental investigation of relationship between trauma and bisphosphonate-related osteonecrosis. Niger J Clin Pract 2014;17:559-64.
16. Keskinrüzgar A, Yanık S, Aras MH, Çetiner S. Teriparatide [parathyroid hormone (1-34)] and dentistry. Acta Odontol Turca 2015;32:165-70.
17. Conte Neto N, Spolidorio LC, Andrade CR, S Bastos A, Guimaraes M, Marcantonio E. Experimental development of bisphosphonate‐related osteonecrosis of the jaws in rodents. Int J Exp Pathol 2013;94:65-73.
18. Ersan N, Van Ruijven LJ, Bronckers AL, Olgaç V, İlgüy D, Everts V. Teriparatide and the treatment of bisphosphonate-related osteonecrosis of the jaw: a rat model. Dentomaxillofac Radiol 2014;43:20130144.
19. Ertaş ET, Atıcı MY. Bisphosphonates and osteonecrosis of the jaws. Selcuk Dent J 2015; 2:91-100.
20. Bianchi SD, Scoletta M, Cassione FB, Migliaretti G, Mozatti M. Computerized tomographic findings in bisphosphonate-associated osteonecrosis of the jaw in patients with cancer. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2007;104:249-58.
21. Bisdas S, Pinho NC, Smolarz A, Sader R, Vogl TJ, Mack MG. Biphosphonate-induced osteonecrosis of the jaws: CT and MRI spectrum of findings in 32 patients. Clin Radiol 2008;63:71-7.
22. Ali EM, Burak CA, Cemil IS, Demircan S, Soluk M, Kasapoğlu 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: 879-83.