THE EFFECT OF SYSTEMIC ZOLEDRONIC ACID ON THE HEALING POTENTIAL OF RATS WITH EXPERIMENTAL PERIODONTITIS

Yıl 2023, Cilt: 6 Sayı: 2, 153 - 159, 26.06.2023

Arzu Morçiçek , Ali Çekici , Vakur Olgaç

https://doi.org/10.26650/JARHS2023-1233253

Öz

Objective: In this study, our goal was to observe the effect of zoledronic acid histopathologically, which is used without removing the periodontitis agent, on the healing potential of the tissue after the experimental periodontitis formation in an animal model.
Material and Method: 30 adult male Sprague-Dawley rats were divided into 2 groups as bisphosphonate users and non-users. At the beginning of the experiment, all rats were put under anesthesia, and 5.0 silk sutures were placed around their right upper first molars. No suture was placed around the left upper first molar teeth. It was waited for 3 weeks after the
placement of the sutures. After experimental periodontitis was observed in the animals on the 21st day, 7.5uq/kg zoledronic acid was injected intramuscularly for 6 weeks in the animals in the experimental group. After intramuscular drug administration once a week for 6 weeks, weekly weight monitoring was performed on days 0, 7, 14, 21, 28, and 35 and noted in the experimental group rats. At the end of 6 weeks, the sutures were removed under the anesthesia from the experimental group animals whose last drug injections were completed and the control group animals that were administered 0.9% saline on the same days. A recovery period of two weeks was expected after which all animals were sacrificed.
Results: Zoledronic acid was used in the histological evaluation results, and experimental inflammation, necrosis, periodontal space and epithelial proliferation in the group with periodontitis statistically significant p<0.05 was found to be higher.
Conclusion: When evaluated clinically, positive effects on wound healing were observed in rats treated with bisphosphonate-derived drugs by treating existing periodontitis prior to drug administration.

Anahtar Kelimeler

Zoledronic acid, rat, experimental periodontitis, osteonecrosis, histology

SİSTEMİK OLARAK KULLANILAN ZOLEDRONİK ASİTİN, DENEYSEL PERİODONTİTİS OLUŞTURULAN SIÇANLARDA İYİLEŞME POTANSİYELİ ÜZERİNE ETKİSİNİN İNCELENMESİ

Öz

Amaç: Bu çalışmada amacımız hayvan modelinde deneysel periodontitis oluşumundan sonra, periodontitis etkeni kaldırılmadan kullandırılan zoledronik asidin, periodontitis etkeni ortadan kaldırıldıktan sonra dokunun iyileşme potansiyeli üzerindeki etkisini histopatolojik olarak gözlemlemeyi hedeflemektir.
Gereç ve Yöntem: Sprague-Dawley cinsi 30 adet yetişkin erkek sıçan bifosfanat kullanan ve kullanmayan olarak 2 gruba ayrılmıştır. Deney başlangıcında tüm sıçanlara, anestezi altında, sağ üst 1.molar dişlerinin etrafına 5.0 ipek dikiş yerleştirilmiştir. Sol üst 1. molar dişlere ise herhangi bir uygulama yapılmamıştır. Dikişlerin yerleştirilmesinden sonra 3 hafta beklenilmiştir. 21. günde hayvanlarda deneysel periodontitis gözlendikten sonra deney grubundaki hayvanlara kas içi 6 hafta boyunca 7,5uq/kg zoledronik asit enjekte edilmiştir. 0., 7., 14., 21., 28., ve 35.günlerde; 6 hafta boyunca, haftada bir, kas içi ilaç verilmesinden sonra deney grubu sıçanlarında, haftalık ağırlık takibi yapılmıştır ve not edilmiştir. Son ilaç enjeksiyonları tamamlanan deney grubu hayvanlarının ve aynı günlerde %0,9 serum fizyolojik uygulanan kontrol grubu hayvanlarının 6 hafta sonunda, anestezi altında yerleştirilen dikişleri kaldırılmıştır. İki haftalık iyileşme süresi için beklenilmiş ve bu iki hafta içinde de deney grubundaki hayvanlara zoledronik asit enjekte edilmiştir.
Bulgular: Histolojik değerlendirme sonuçlarında zoledronik asit kullanılmış ve deneysel periodontitis oluşturulan grupta iltihap, nekroz, periodontal aralık ve epitel proliferasyonu istatiksel anlamlı p<0,05 olarak daha fazla bulunmuştur
Sonuç: Klinik açıdan değerlendirildiğinde, bifosfanat türev ilaç kullandırılmış sıçanlarda, ilaç kullanımı öncesinde, var olan periodontitisin tedavi edilmesinin yara iyileşmesi üzerinde olumlu etkileri gözlenmiştir.

Anahtar Kelimeler

Zoledronik asit, sıçan, deneysel periodontitis, osteonekroz, histoloji

Destekleyen Kurum

kendim

Kaynakça

• Ficarra G, Beninati F, Rubino I, Vannucchi A, Longo, Tonelli P. GOsteonecrosis of the jaws in periodontal patients with a history of bisphosphonates treatment J Clin Periodontol 2005;32(11):1123-8. google scholar
• Saad F, Brown JE, Van Poznak C, Ibrahim T, Stemmer SM, Stopeck AT et al. Incidence, risk factors, and outcomes of osteonecrosis of the jaw: integrated analysis from three blinded active-controlled phase III trials in cancer patients with bone metastases. Ann Oncol 2012;(23):1341-7. google scholar
• Vahtsevanos K, Kyrgidis A, Verrou E, Katodritou E, Triaridis S, Andreadis CG et al. Longitudinal cohort study of risk factors in cancer patients of bisphosphonate-related osteonecrosis of the jaw. J Clin Oncol 2009;(27):5356-62 google scholar
• Sonis ST, Watkins BA, Lyng GD, Lerman MA, Anderson KC. Bony changes in the jaws of rats treated with zoledronic acid and dexamethasone before dental extractions mimic bisphosphonate-related osteonecrosis in cancer patients Oral Oncol 2009;45(2):164-72. google scholar
• Kim RH, Lee RS, Williams D, Bae S, Woo J, Lieberman M et.al. Bisphosphonates induce senescence in normal human oral keratinocytes. J Dent Res 2011;90(6):810-6. google scholar
• Landesberg R, Cozin M, Cremers S, Woo V, Kousteni S, Sinha S et al. Inhibition of oral mucosal cell wound healing by bisphosphonates. J Maxillofac Surg 2008;66(5):839-47. google scholar
• Li CL, Lu WW, Seneviratne CJ, Leung WK, Zwahlen RA, Zheng LW et al. Role of periodontal disease in bisphosphonates-related osteonecrosis of the jaws in ovariectomized rats. Clin Oral Implants Res 2016;27(1):1-6. google scholar
• 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(8):1871-81 google scholar
• Page RC, Shroeder HE. Pathogenesis of inflammatory periodontal disease. A summary of current work. Lab Invest 1976;34(3):235-49. google scholar
• Seymour GJ, Taylor JJ. Shouts and whispers: an introduction to immunoregulation in periodontal disease. J Clin Periodontol 2004;35(3):9-13. google scholar
• Leira Y, Iglesias-Rey R, Gomez-Lado N, Aguiar P , Sobrino T, D'Aiuto F et al. Periodontitis and vascular inflammatory biomarkers: an experimental in vivo study in rats. Odotonlogy 2020;108(2):202-12. google scholar
• Rusell RGG. Bisphonates from bench to bedside. Ann NY Acad Sci 2006;1068:367-401. google scholar
• Fleisch H. Development of bisphosphonates. Breast Cancer Res 2002;4(1):30-4. google scholar
• Russell RGG, Watts NB, Ebetino FH, Rogers MJ. Mechanisms of action of bisphosphonates: Similarities and differences and their potential influence on clinical efficacy. Osteoporos Int 2008;(19):733-59. google scholar
• Cheng A, Mavrokokki T, Carter G, Stein B, Fazzalari N, Wilson D, et al. The dental implications of bisphosphpnates and bone disease. Aust Dent J 2005;50(4 Suppl 2):S4-13. google scholar
• Russell RGG. Bisphosphonates: The first 40 years. Bone 2011;49(1):2-19. google scholar
• Marx RE, Cillo JE, Ulloa JJ. Oral bishosphonate-induced osteonecrosis: risk factors, prediction of risk using serum CTX testing, prevention and treatment. J Oral Maxillofac Surg 2009;(67):2-12. google scholar
• Russell RGG. Bishosphonates: Mode of action and pharmocology. Am Acad J Pediatr 2007;119 Suppl 2:150-62. google scholar
• Chen T, Berenson J, Vescio R, Swift R, Gilchick A, Goodin S et al. Pharmacokinetics and pharmacodynamics of zoledronic acid in cancer patients with bone metastases. J Clin Pharmacol 2002;42(11):1228-36 google scholar
• Nobuyuki H, Hiraga T, Williams PJ, Niewolna M, Shimizu N, Mundy GR, et al. The bisphosphonate zoledronic acid inhibits metastases to bone and liver with suppression of osteopontin production in mouse mammary tumor. J Bone Miner Res 2001;16(Suppl 1):S191. google scholar
• Senaratne SG, Mansi JL, Colston KW. The bisphosphonate zoledronic acid impairs membrane localisation and induce cytochrome c release in breast cancer cells. Br J Cancer 2002;86(9):1479-86. google scholar
• Vaycan HS. Sistemik kullanılan zoledronik asitin var olan deneysel periodontitis üzerine etkisinin histomorfometrik olarak incelenmesi. İstanbul Üniversitesi Sağlık Bilimleri Enstitüsü. Doktora Tezi. İstanbul 2020. google scholar