Year 2021, Volume 31 , Issue 1, Pages 115 - 123 2021-01-15

İLACA BAĞLI ÇENE KEMİĞİ OSTEONEKROZU: BİR DERLEME

Mehmet Melih ÖMEZLİ [1] , Ferhat AYRANCI [2] , Damla TORUL [3] , Emine ÖRNEK AKDOĞAN [4]


İlaca Bağlı Çene Kemiği Osteonekrozu: Bir Derleme İlaca Bağlı Çene Kemiği Osteonekrozu (MRONJ) bifosfonatlar yanında antiosteoklastik ve antianjiyojenik aktiviteye sahip ilaçların kullanımı sonucu ortaya çıkan, maksilla ve mandibulada nekrotik kemik varlığı ile karakterize bir komplikasyondur. Hem hekimler hem de hastalar için ciddi bir problem oluşturan bu özgün komplikasyonun optimum düzeyde yönetimini sağlayarak hastaların ekonomik ve sosyal mağduriyetlerini önleyecek tedavi protokolü ile ilgili bir fikir birliği bulunmamaktadır. Bu derlemenin amacı ilaca bağlı çene kemiği osteonekrozunun etyopatolojisi ve güncel tedavi stratejilerini literatür ışığında sunmaktır. Anahtar kelimeler: osteonekroz, bifosfonat, denosumab, bevacizumab Medication Related Osteonecrosis of the Jawbones: A Review ABSTRACT Medication Related Osteonecrosis of the Jawbones: A Review Medication Related Osteonecrosis of the Jaws (MRONJ) is a complication characterized by the appearance of necrotic bone in the maxilla and mandible, resulting from the use of bisphosphonates as well as drugs with antiosteoclastic and antiangiogenic activity. No consensus has been reach regarding the treatment protocol that will prevent the economic and social burden of the patients by providing optimum management of this unique complication which constitutes a serious problem for both physicians and patients. The aim of this review is to present the etiopathology and current treatment strategies of Medication Related Osteonecrosis of the Jaws in the light of the literature. Keywords: osteonecrosis, bisphosphonate, denosumab, bevacizumab
osteonekroz, bifosfonat, denosumab
  • 1. Aslan Ö, Vural H, Kömürcü Ş, Özet A. Kemoterapi Alan kanser hastalarina verilen eğitimin kemoterapi semptomlarina etkisi. CÜ Hemsirelik Yüksekokulu Derg 2006;10:15-28.
  • 2. Ribeiro GH, Chrun ES, Dutra KL, Daniel FI, Grando LJ. Osteonecrosis of the jaws: a review and update in etiology and treatment. Braz J Otorhinolaryngol 2018;84:102-8.
  • 3. Manea HC, Urechescu HC, Balica NC, Pricop MO, Baderca F, Poenaru M, Horhat ID, Jifcu EM, Closca RM, Sarau CA. Bisphosphonates-induced osteonecrosis of the jaw - epidemiological, clinical and histopathological aspects. Rom J Morphol Embryol 2018;59:825-31.
  • 4. Marx RE. Pamidronate (Aredia) and zoledronate (Zometa) induced avascular necrosis of the jaws: a growing epidemic. J Oral Maxillofac Surg 2003;61:1115-7.
  • 5. Crepin S, Laroche ML, Sarry B, Merle L. Osteonecrosis of the jaw induced by clodronate, an alkylbiphosphonate: case report and literature review. Eur J Clin Pharmacol 2010;66:547-54.
  • 6. Ruggiero SL, Dodson TB, Assael LA, Landesberg R, Marx RE, Mehrotra B. American Association of Oral and Maxillofacial Surgeons position paper on bisphosphonate-related osteonecrosis of the jaw - 2009 update. Aust Endod J 2009;35:119-30.
  • 7. Estilo CL, Fornier M, Farooki A, Carlson D, Bohle G, 3rd, Huryn JM. Osteonecrosis of the jaw related to bevacizumab. J Clin Oncol 2008;26:4037-8.
  • 8. King R, Tanna N, Patel V. Medication-related osteonecrosis of the jaw unrelated to bisphosphonates and denosumab-a review. Oral Surg Oral Med Oral Pathol Oral Radiol 2019;127:289-99.
  • 9. Ruggiero SL, Dodson TB, Fantasia J, Goodday R, Aghaloo T, Mehrotra B, O'Ryan F. 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.
  • 10. Topaloglu G, Koseoglu OT, Karaca C, Kosemehmetoglu K. The effect of chronic dental inflammation on development of Stage 0 medication-related osteonecrosis of the jaw. J Craniomaxillofac Surg 2017;45:1158-64.
  • 11. Kang MH, Lee DK, Kim CW, Song IS, Jun SH. Clinical characteristics and recurrence-related factors of medication-related osteonecrosis of the jaw. J Korean Assoc Oral Maxillofac Surg 2018;44:225-31.
  • 12. Roelofs AJ, Thompson K, Gordon S, Rogers MJ. Molecular mechanisms of action of bisphosphonates: current status. Clin Cancer Res 2006; 12:6222s-30s.
  • 13. Lemound J, Muecke T, Zeller AN, Lichtenstein J, Eckardt A, Gellrich NC. Nasolabial Flap improves healing in medication-related osteonecrosis of the jaw. J Oral Maxillofac Surg 2018;76:877-85.
  • 14. Wood J, Bonjean K, Ruetz S, Bellahcene A, Devy L, Foidart JM, Castronovo V, Green JR. Novel antiangiogenic effects of the bisphosphonate compound zoledronic acid. J Pharmacol Exp Ther 2002;302:1055-61.
  • 15. Santini D, Vincenzi B, Dicuonzo G, Avvisati G, Massacesi C, Battistoni F, Gavasci M, Rocci L, Tirindelli MC, Altomare V, Tocchini M, Bonsignori M, Tonini G. Zoledronic acid induces significant and long-lasting modifications of circulating angiogenic factors in cancer patients. Clin Cancer Res 2003;9:2893-7.
  • 16. Landesberg R, Cozin M, Cremers S, Woo V, Kousteni S, Sinha S, Garrett-Sinha L, Raghavan S. Inhibition of oral mucosal cell wound healing by bisphosphonates. J Oral Maxillofac Surg 2008; 66:839-47.
  • 17. Reid IR, Bolland MJ, Grey AB. Is bisphosphonate-associated osteonecrosis of the jaw caused by soft tissue toxicity? Bone 2007;41:318-20.
  • 18. Aljohani S, Fliefel R, Ihbe J, Kuhnisch J, Ehrenfeld M, Otto S. What is the effect of anti-resorptive drugs (ARDs) on the development of medication-related osteonecrosis of the jaw (MRONJ) in osteoporosis patients: A systematic review. J Craniomaxillofac Surg 2017;45:1493-502.
  • 19. Yazıcı T, Şentürk MF, Koçer G. İlaca bağlı olarak çene kemiklerinde görülen osteonekroz (mronj) medication related osteonecrosis of the jaws (Mronj). SDÜ Saglık Bılım Derg 2017;2:50.
  • 20. Cummings SR, San Martin J, McClung MR, Siris ES, Eastell R, Reid IR, Delmas P, Zoog HB, Austin M, Wang A, Kutilek S, Adami S, Zanchetta J, Libanati C, Siddhanti S, Christiansen C. Denosumab for prevention of fractures in postmenopausal women with osteoporosis. N Engl J Med 2009;361:756-65.
  • 21. Van Poznak CH, Temin S, Yee GC, Janjan NA, Barlow WE, Biermann JS, Bosserman LD, Geoghegan C, Hillner BE, Theriault RL, Zuckerman DS, Von Roenn JH. American Society of Clinical Oncology executive summary of the clinical practice guideline update on the role of bone-modifying agents in metastatic breast cancer. J Clin Oncol 2011;29:1221-7.
  • 22. Fizazi K, Carducci M, Smith M, Damiao R, Brown J, Karsh L, Milecki P, Shore N, Rader M, Wang H, Jiang Q, Tadros S, Dansey R, Goessl C. Denosumab versus zoledronic acid for treatment of bone metastases in men with castration-resistant prostate cancer: a randomised, double-blind study. Lancet 2011;377:813-22.
  • 23. Whyte MP. The long and the short of bone therapy. N Engl J Med 2006;354:860-3.
  • 24. Egloff-Juras C, Gallois A, Salleron J, Massard V, Dolivet G, Guillet J, Phulpin B. Denosumab-related osteonecrosis of the jaw: A retrospective study. J Oral Pathol Med 2018;47:66-70.
  • 25. Kerbel R, Folkman J. Clinical translation of angiogenesis inhibitors. Nature Reviews Cancer 2002;2:727-39.
  • 26. Bernold DM, Sinicrope FA. Advances in chemotherapy for colorectal cancer. Clin Gastroenterol Hepatol 2006;4:808-21.
  • 27. Li M, Kroetz DL. Bevacizumab-induced hypertension: Clinical presentation and molecular understanding. Pharmacol Ther 2018;182:152-160.
  • 28. Fleissig Y, Regev E, Lehman H. Sunitinib related osteonecrosis of jaw: a case report. Oral Surg Oral Med Oral Pathol Oral Radiol 2012;113:e1-3.
  • 29. Demlova R, Turjap M, Pes O, Kostolanska K, Jurica J. Therapeutic Drug monitoring of sunitinib in gastrointestinal stromal tumors and metastatic renal carcinoma in adults - a review. Ther Drug Monit 2020;42:20-32.
  • 30. Paech F, Abegg VF, Duthaler U, Terracciano L, Bouitbir J, Krahenbuhl S. Sunitinib induces hepatocyte mitochondrial damage and apoptosis in mice. Toxicology 2018;409:13-23.
  • 31. Hoefert S, Eufinger H. Sunitinib may raise the risk of bisphosphonate-related osteonecrosis of the jaw: presentation of three cases. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2010;110:463-9.
  • 32. Otto S, Pautke C, Van den Wyngaert T, Niepel D, Schiodt M. Medication-related osteonecrosis of the jaw: Prevention, diagnosis and management in patients with cancer and bone metastases. Cancer Treat Rev 2018;69:177-87.
  • 33. Cardoso CL, Barros CA, Curra C, Fernandes LM, Franzolin SO, Junior JS, De Antoni CC, Curi MM. Radiographic findings in patients with medication-related osteonecrosis of the jaw. Int J Dent 2017;2017:3190301.
  • 34. Stockmann P, Hinkmann FM, Lell MM, Fenner M, Vairaktaris E, Neukam FW, Nkenke E. Panoramic radiograph, computed tomography or magnetic resonance imaging. Which imaging technique should be preferred in bisphosphonate-associated osteonecrosis of the jaw? A prospective clinical study. Clin Oral Investig 2010;14:311-7.
  • 35. Treister N, Sheehy N, Bae EH, Friedland B, Lerman M, Woo S. Dental panoramic radiographic evaluation in bisphosphonate-associated osteonecrosis of the jaws. Oral Dis 2009;15:88-92.
  • 36. Ogura I, Sasaki Y, Kameta A, Sue M, Oda T. Characteristic Multimodal imaging of medication-related osteonecrosis of the jaw: comparison between oral and parenteral routes of medication administration. pol J Radiol 2017;82:551-60.
  • 37. Zirk M, Buller J, Zoller JE, Heneweer C, Kubler N, Lentzen MP. Volumetric analysis of MRONJ lesions by semiautomatic segmentation of CBCT images. Oral Maxillofac Surg 2019;23:465-72.
  • 38. Shuster A, Reiser V, Trejo L, Ianculovici C, Kleinman S, Kaplan I. Comparison of the histopathological characteristics of osteomyelitis, medication-related osteonecrosis of the jaw, and osteoradionecrosis. Int J Oral Maxillofac Surg 2019;48:17-22.
  • 39. Troeltzsch M, Woodlock T, Kriegelstein S, Steiner T, Messlinger K, Troeltzsch M. Physiology and pharmacology of nonbisphosphonate drugs implicated in osteonecrosis of the jaw. J Can Dent Assoc 2012;78:c85.
  • 40. Hansen T, Kunkel M, Weber A, James Kirkpatrick C. Osteonecrosis of the jaws in patients treated with bisphosphonates - histomorphologic analysis in comparison with infected osteoradionecrosis. J Oral Pathol Med 2006;35:155-60.
  • 41. Çapar Gd, Cabbar F, Yalçin M, Tomruk CÖ. İlaçlara bağli çene kemiği osteonekrozu: derleme. Atatürk Üniversitesi Diş Hekimliği Fakültesi Dergisi 2015;13:118-129.
  • 42. Maluf G, Caldas RJ, Silva Santos PS. Use of leukocyte- and platelet-rich fibrin in the treatment of medication-related osteonecrosis of the jaws. J Oral Maxillofac Surg 2018;76:88-96.
  • 43. Wazzan T, Kashtwari D, Almaden WF, Gong Y, Chen Y, Moreb J, Katz J. Radiographic bone loss and the risk of medication-related osteonecrosis of the jaw (MRONJ) in multiple myeloma patients-A retrospective case control study. Spec Care Dentist 2018;38:356-61.
  • 44. Saad F, Brown JE, Van Poznak C, Ibrahim T, Stemmer SM, Stopeck AT, Diel IJ, Takahashi S, Shore N, Henry DH, Barrios CH, Facon T, Senecal F, Fizazi K, Zhou L, Daniels A, Carriere P, Dansey R. 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.
  • 45. Filleul O, Crompot E, Saussez S. Bisphosphonate-induced osteonecrosis of the jaw: a review of 2,400 patient cases. J Cancer Res Clin Oncol 2010;136:1117-24.
  • 46. Scagliotti GV, Hirsh V, Siena S, Henry DH, Woll PJ, Manegold C, Solal-Celigny P, Rodriguez G, Krzakowski M, Mehta ND, Lipton L, Garcia-Saenz JA, Pereira JR, Prabhash K, Ciuleanu TE, Kanarev V, Wang H, Balakumaran A, Jacobs I. Overall survival improvement in patients with lung cancer and bone metastases treated with denosumab versus zoledronic acid: subgroup analysis from a randomized phase 3 study. J Thorac Oncol 2012;7:1823-9.
  • 47. Henry DH, Costa L, Goldwasser F, Hirsh V, Hungria V, Prausova J, Scagliotti GV, Sleeboom H, Spencer A, Vadhan-Raj S, von Moos R, Willenbacher W, Woll PJ, Wang J, Jiang Q, Jun S, Dansey R, Yeh H. Randomized, double-blind study of denosumab versus zoledronic acid in the treatment of bone metastases in patients with advanced cancer (excluding breast and prostate cancer) or multiple myeloma. J Clin Oncol 2011;29:1125-32.
  • 48. Rao NJ, Yu RQ, Wang JY, Helm A, Zheng LW. Effect of Periapical Diseases in Development of MRONJ in Immunocompromised Mouse Model. Biomed Res Int 2019;2019:1271492.
  • 49. Katz J, Gong Y, Salmasinia D, Hou W, Burkley B, Ferreira P, Casanova O, Langaee TY, Moreb JS. Genetic polymorphisms and other risk factors associated with bisphosphonate induced osteonecrosis of the jaw. Int J Oral Maxillofac Surg 2011;40:605-11.
  • 50. Nicoletti P, Cartsos VM, Palaska PK, Shen Y, Floratos A, Zavras AI. Genomewide pharmacogenetics of bisphosphonate-induced osteonecrosis of the jaw: the role of RBMS3. Oncologist 2012;17:279-87.
  • 51. Park W, Kim NK, Kim MY, Rhee YM, Kim HJ. Osteonecrosis of the jaw induced by oral administ- ration of bisphosphonates in Asian population: five cases. Osteoporos Int 2010;21: 527-33.
  • 52. Barrett-Connor E, Siris ES, Wehren LE, Miller PD, Abbott TA, Berger ML, Santora AC, Sherwood LM. Osteoporosis and fracture risk in women of different ethnic groups. J Bone Miner Res 2005;20:185-94.
  • 53. Dimopoulos MA, Kastritis E, Bamia C, Melakopoulos I, Gika D, Roussou M, Migkou M, Eleftherakis-Papaiakovou E, Christoulas D, Terpos E, Bamias A. Reduction of osteonecrosis of the jaw (ONJ) after implementation of preventive measures in patients with multiple myeloma treated with zoledronic acid. Ann Oncol 2009;20:117-20.
  • 54. Heufelder MJ, Hendricks J, Remmerbach T, Frerich B, Hemprich A, Wilde F. Principles of oral surgery for prevention of bisphosphonate-related osteonecrosis of the jaw. Oral Surg Oral Med Oral Pathol Oral Radiol 2014;117:e429-35.
  • 55. Abt E. The Risk of Medication-Related Osteonecrosis of the jaw after dental extraction is higher for patients on intravenous as compared with oral antiresorptive drugs. J Evid Based Dent Pract 2017;17:105-6.
  • 56. Ripamonti CI, Cislaghi E, Mariani L, Maniezzo M. Efficacy and safety of medical ozone (O(3)) delivered in oil suspension applications for the treatment of osteonecrosis of the jaw in patients with bone metastases treated with bisphosphonates: Preliminary results of a phase I-II study. Oral Oncol 2011;47:185-90.
  • 57. Laimer J, Steinmassl O, Hechenberger M, Rasse M, Pikula R, Bruckmoser E. Intraoral Vacuum-Assisted Closure Therapy-A Pilot Study in Medication-Related Osteonecrosis of the Jaw. J Oral Maxillofac Surg 2017;75:2154-61.
  • 58. Nisi M, Karapetsa D, Gennai S, Ramaglia L, Graziani F, Gabriele M. Conservative surgical treatment of medication related osteonecrosis of the jaw (MRONJ) lesions in patients affected by osteoporosis exposed to oral bisphosphonates: 24 months follow-up. J Craniomaxillofac Surg 2018;46:1153-8.
  • 59. Cano-Duran JA, Pena-Cardelles JF, Ortega-Concepcion D, Paredes-Rodriguez VM, Garcia-Riart M, Lopez-Quiles J. The role of Leucocyte-rich and platelet-rich fibrin (L-PRF) in the treatment of the medication-related osteonecrosis of the jaws (MRONJ). J Clin Exp Dent 2017;9:e1051-9.
  • 60. Assaf AT, Zrnc TA, Riecke B, Wikner J, Zustin J, Friedrich RE, Heiland M, Smeets R, Grobe A. Intraoperative efficiency of fluorescence imaging by Visually Enhanced Lesion Scope (VELscope) in patients with bisphosphonate related osteonecrosis of the jaw (BRONJ). J Craniomaxillofac Surg 2014;42:e157-64.
  • 61. Otto S, Baumann S, Ehrenfeld M, Pautke C. Successful surgical management of osteonecrosis of the jaw due to RANK-ligand inhibitor treatment using fluorescence guided bone resection. J Craniomaxillofac Surg 2013;41:694-8.
  • 62. Giudice A, Bennardo F, Barone S, Antonelli A, Figliuzzi MM, Fortunato L. Can Autofluorescence Guide Surgeons in the Treatment of Medication-Related Osteonecrosis of the Jaw? A Prospective Feasibility Study. J Oral Maxillofac Surg 2018;76:982-95.
Primary Language tr
Subjects Dentistry, Oral Surgery and Medicine
Journal Section Derleme
Authors

Orcid: 0000-0002-6606-6593
Author: Mehmet Melih ÖMEZLİ
Institution: ORDU ÜNİVERSİTESİ, DİŞ HEKİMLİĞİ FAKÜLTESİ
Country: Andorra


Orcid: 0000-0001-7126-5696
Author: Ferhat AYRANCI
Institution: ORDU ÜNİVERSİTESİ, DİŞ HEKİMLİĞİ FAKÜLTESİ
Country: Andorra


Orcid: 0000-0003-2323-606X
Author: Damla TORUL
Institution: ORDU ÜNİVERSİTESİ, DİŞ HEKİMLİĞİ FAKÜLTESİ
Country: Andorra


Orcid: 0000-0002-0701-1103
Author: Emine ÖRNEK AKDOĞAN
Institution: ORDU ÜNİVERSİTESİ, DİŞ HEKİMLİĞİ FAKÜLTESİ
Country: Andorra


Dates

Publication Date : January 15, 2021

Bibtex @review { ataunidfd706825, journal = {Atatürk Üniversitesi Diş Hekimliği Fakültesi Dergisi}, issn = {1300-9044}, eissn = {2667-5161}, address = {}, publisher = {Ataturk University}, year = {2021}, volume = {31}, pages = {115 - 123}, doi = {10.17567/ataunidfd.706825}, title = {İLACA BAĞLI ÇENE KEMİĞİ OSTEONEKROZU: BİR DERLEME}, key = {cite}, author = {Ömezli, Mehmet Melih and Ayrancı, Ferhat and Torul, Damla and Örnek Akdoğan, Emine} }
APA Ömezli, M , Ayrancı, F , Torul, D , Örnek Akdoğan, E . (2021). İLACA BAĞLI ÇENE KEMİĞİ OSTEONEKROZU: BİR DERLEME . Atatürk Üniversitesi Diş Hekimliği Fakültesi Dergisi , 31 (1) , 115-123 . DOI: 10.17567/ataunidfd.706825
MLA Ömezli, M , Ayrancı, F , Torul, D , Örnek Akdoğan, E . "İLACA BAĞLI ÇENE KEMİĞİ OSTEONEKROZU: BİR DERLEME" . Atatürk Üniversitesi Diş Hekimliği Fakültesi Dergisi 31 (2021 ): 115-123 <https://dergipark.org.tr/en/pub/ataunidfd/issue/60082/706825>
Chicago Ömezli, M , Ayrancı, F , Torul, D , Örnek Akdoğan, E . "İLACA BAĞLI ÇENE KEMİĞİ OSTEONEKROZU: BİR DERLEME". Atatürk Üniversitesi Diş Hekimliği Fakültesi Dergisi 31 (2021 ): 115-123
RIS TY - JOUR T1 - İLACA BAĞLI ÇENE KEMİĞİ OSTEONEKROZU: BİR DERLEME AU - Mehmet Melih Ömezli , Ferhat Ayrancı , Damla Torul , Emine Örnek Akdoğan Y1 - 2021 PY - 2021 N1 - doi: 10.17567/ataunidfd.706825 DO - 10.17567/ataunidfd.706825 T2 - Atatürk Üniversitesi Diş Hekimliği Fakültesi Dergisi JF - Journal JO - JOR SP - 115 EP - 123 VL - 31 IS - 1 SN - 1300-9044-2667-5161 M3 - doi: 10.17567/ataunidfd.706825 UR - https://doi.org/10.17567/ataunidfd.706825 Y2 - 2020 ER -
EndNote %0 Atatürk Üniversitesi Diş Hekimliği Fakültesi Dergisi İLACA BAĞLI ÇENE KEMİĞİ OSTEONEKROZU: BİR DERLEME %A Mehmet Melih Ömezli , Ferhat Ayrancı , Damla Torul , Emine Örnek Akdoğan %T İLACA BAĞLI ÇENE KEMİĞİ OSTEONEKROZU: BİR DERLEME %D 2021 %J Atatürk Üniversitesi Diş Hekimliği Fakültesi Dergisi %P 1300-9044-2667-5161 %V 31 %N 1 %R doi: 10.17567/ataunidfd.706825 %U 10.17567/ataunidfd.706825
ISNAD Ömezli, Mehmet Melih , Ayrancı, Ferhat , Torul, Damla , Örnek Akdoğan, Emine . "İLACA BAĞLI ÇENE KEMİĞİ OSTEONEKROZU: BİR DERLEME". Atatürk Üniversitesi Diş Hekimliği Fakültesi Dergisi 31 / 1 (January 2021): 115-123 . https://doi.org/10.17567/ataunidfd.706825
AMA Ömezli M , Ayrancı F , Torul D , Örnek Akdoğan E . İLACA BAĞLI ÇENE KEMİĞİ OSTEONEKROZU: BİR DERLEME. Ata Diş Hek Fak Derg. 2021; 31(1): 115-123.
Vancouver Ömezli M , Ayrancı F , Torul D , Örnek Akdoğan E . İLACA BAĞLI ÇENE KEMİĞİ OSTEONEKROZU: BİR DERLEME. Atatürk Üniversitesi Diş Hekimliği Fakültesi Dergisi. 2021; 31(1): 115-123.
IEEE M. Ömezli , F. Ayrancı , D. Torul and E. Örnek Akdoğan , "İLACA BAĞLI ÇENE KEMİĞİ OSTEONEKROZU: BİR DERLEME", Atatürk Üniversitesi Diş Hekimliği Fakültesi Dergisi, vol. 31, no. 1, pp. 115-123, Jan. 2021, doi:10.17567/ataunidfd.706825

Authors of the Article
Mehmet Melih ÖMEZLİ [1]
Ferhat AYRANCI [2]
Damla TORUL [3]
Emine ÖRNEK AKDOĞAN [4]