{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T19:49:15Z","timestamp":1791229755396,"version":"4.1.0"},"reference-count":100,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2023,4,21]],"date-time":"2023-04-21T00:00:00Z","timestamp":1682035200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Radiotherapy (RT) or concurrent chemoradiotherapy (CCRT) is the cornerstone of organ-sparing or adjuvant therapy for nearly all head and neck cancers. Unfortunately, aggressive RT or CCRT can result in severe late toxicities, such as osteoradionecrosis of the jaws (ORNJ). The incidence of ORNJ is currently less than 5\u20136% due to advances in dental preventive care programs, RT planning systems, and RT techniques. Although numerous patient-, tumor-, and treatment-related factors may influence the incidence rates of ORNJ, RT modality (equipment), technique, and dose-volume-related factors are three of the most influential factors. This is mainly because different RT equipment and techniques have different levels of success at delivering the prescribed dose to the focal volume of the treatment while keeping the \u201corgan at risk\u201d safe. ORNJ risk is ultimately determined by mandibular dose, despite the RT technique and method being known predictors. Regardless of the photon delivery method, the radiobiological effects will be identical if the total dose, dose per fraction, and dose distribution within the tissue remain constant. Therefore, contemporary RT procedures mitigate this risk by reducing mandibular dosages rather than altering the ionizing radiation behavior in irradiated tissues. In light of the paucity of studies that have examined the impact of RT modality, technique, and dose-volume-related parameters, as well as their radiobiological bases, the present review aims to provide a comprehensive overview of the published literature on these specific issues to establish a common language among related disciplines and provide a more reliable comparison of research results.<\/jats:p>","DOI":"10.3390\/jcm12083025","type":"journal-article","created":{"date-parts":[[2023,4,21]],"date-time":"2023-04-21T06:06:18Z","timestamp":1682057178000},"page":"3025","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":67,"title":["Review of Osteoradionecrosis of the Jaw: Radiotherapy Modality, Technique, and Dose as Risk Factors"],"prefix":"10.3390","volume":"12","author":[{"given":"Erkan","family":"Topkan","sequence":"first","affiliation":[{"name":"Department of Radiation Oncology, Medical Faculty, Baskent University, Adana 01120, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5361-364X","authenticated-orcid":false,"given":"Ahmet","family":"Kucuk","sequence":"additional","affiliation":[{"name":"Clinics of Radiation Oncology, Mersin City Education and Research Hospital, Mersin 33160, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Efsun","family":"Somay","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Baskent University, Ankara 06490, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0633-5648","authenticated-orcid":false,"given":"Busra","family":"Yilmaz","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Radiology, Faculty of Dentistry, Baskent University, Ankara 06490, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Berrin","family":"Pehlivan","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Bahcesehir University, Istanbul 34349, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8087-3140","authenticated-orcid":false,"given":"Ugur","family":"Selek","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, School of Medicine, Koc University, Istanbul 34450, Turkey"},{"name":"Department of Radiation Oncology, MD Anderson Cancer Center, The University of Texas, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"87","DOI":"10.3322\/caac.21262","article-title":"Global cancer statistics, 2012","volume":"65","author":"Torre","year":"2015","journal-title":"CA Cancer J. Clin."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Anderson, G., Ebadi, M., Vo, K., Novak, J., Govindarajan, A., and Amini, A. (2021). An Updated Review on Head and Neck Cancer Treatment with Radiation Therapy. Cancers, 13.","DOI":"10.3390\/cancers13194912"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1053\/j.seminoncol.2019.07.002","article-title":"Modern radiotherapy for head and neck cancer","volume":"46","author":"Alterio","year":"2019","journal-title":"Semin. Oncol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1016\/j.radonc.2017.12.011","article-title":"Palliative radiotherapy for locally advanced non-metastatic head and neck cancer: A systematic review","volume":"126","author":"Kelly","year":"2018","journal-title":"Radiother Oncol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/j.radonc.2021.01.013","article-title":"Meta-analysis of chemotherapy in head and neck cancer (MACH-NC): An update on 107 randomized trials and 19,805 patients, on behalf of MACH-NC Group","volume":"156","author":"Lacas","year":"2021","journal-title":"Radiother. Oncol. J. Eur. Soc. Ther. Radiol. Oncol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.ctrv.2017.07.003","article-title":"Treatment of late sequelae after radiotherapy for head and neck cancer","volume":"59","author":"Strojan","year":"2017","journal-title":"Cancer Treat. Rev."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2918","DOI":"10.1002\/cam4.1221","article-title":"Common oral complications of head and neck cancer radiation therapy: Mucositis, infections, saliva change, fibrosis, sensory dysfunctions, dental caries, periodontal disease, and osteoradionecrosis","volume":"6","author":"Sroussi","year":"2017","journal-title":"Cancer Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1373","DOI":"10.1080\/0284186X.2019.1643037","article-title":"Osteoradionecrosis of the mandible after radiotherapy for head and neck cancer: Risk factors and dose-volume correlations","volume":"58","author":"Hansen","year":"2019","journal-title":"Acta Oncol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1016\/j.ijrobp.2019.02.044","article-title":"HOPON (Hyperbaric Oxygen for the Prevention of Osteoradionecrosis): A randomized controlled trial of hyperbaric oxygen to prevent osteoradionecrosis of the irradiated mandible after dentoalveolar surgery","volume":"104","author":"Shaw","year":"2019","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1016\/j.oraloncology.2012.01.016","article-title":"Effectiveness of intensity-modulated and image-guided radiotherapy to spare the mandible from excessive radiation","volume":"48","author":"Nguyen","year":"2012","journal-title":"Oral Oncol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"3691","DOI":"10.1002\/cncr.30803","article-title":"Osteoradionecrosis of the mandible in patients with oropharyngeal carcinoma treated with intensity-modulated radiotherapy","volume":"123","author":"Caparrotti","year":"2017","journal-title":"Cancer"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/j.radonc.2022.10.011","article-title":"Osteoradionecrosis rate in oropharynx cancer treated with dose volume histogram-based constraints","volume":"176","author":"Lee","year":"2022","journal-title":"Radiother. Oncol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/S0360-3016(03)00405-X","article-title":"Intensity-modulated radiation therapy for head-and-neck cancer: The UCSF experience focusing on target volume delineation","volume":"57","author":"Lee","year":"2003","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1186\/1748-717X-8-279","article-title":"CBCT-based volumetric and dosimetric variation evaluation of volumetric modulated arc radiotherapy in the treatment of nasopharyngeal cancer patients","volume":"8","author":"Jin","year":"2013","journal-title":"Radiat. Oncol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1001\/jamaoto.2022.4165","article-title":"Osteoradionecrosis of the jaw following proton radiation therapy for patients with head and neck cancer","volume":"149","author":"Singh","year":"2023","journal-title":"JAMA Otolaryngol. Head Neck Surg."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1206","DOI":"10.1016\/j.ijrobp.2020.12.043","article-title":"Osteoradionecrosis: Exposing the evidence not the bone","volume":"109","author":"Frankart","year":"2021","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1016\/j.bjoms.2020.10.006","article-title":"Timing of dental extractions in patients undergoing radiotherapy and the incidence of osteoradionecrosis: A systematic review and meta-analysis","volume":"59","author":"Beaumont","year":"2021","journal-title":"Br. J. Oral Maxillofac. Surg."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1595","DOI":"10.1111\/odi.13485","article-title":"Tooth extraction before radiotherapy is a risk factor for developing osteoradionecrosis of the jaws: A systematic review","volume":"27","author":"Lajolo","year":"2021","journal-title":"Oral Dis."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"672","DOI":"10.1016\/j.oooo.2016.07.020","article-title":"Preradiotherapy dental extractions and health-related quality of life","volume":"122","author":"Beech","year":"2016","journal-title":"Oral Surg. Oral Med. Oral Pathol. Oral Radiol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1016\/j.ijrobp.2005.10.021","article-title":"Osteoradionecrosis prevention myths","volume":"64","author":"Wahl","year":"2006","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1002\/hed.2890060404","article-title":"Osteoradionecrosis: Predisposing factors and outcomes of therapy","volume":"6","author":"Beumer","year":"1984","journal-title":"Head Neck Surg."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1038\/sj.bdj.2015.29","article-title":"A review of dental treatment of head and neck cancer patients before, during and after radiotherapy: Part 2","volume":"218","author":"Jawad","year":"2015","journal-title":"Br. Dent. J."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1016\/j.clon.2016.03.002","article-title":"Current concepts in osteoradionecrosis after head and neck radiotherapy","volume":"28","author":"Dhanda","year":"2016","journal-title":"Clin. Oncol. (R Coll. Radiol.)."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1007\/0-387-25354-8_8","article-title":"Radiation-induced skeletal injury","volume":"128","author":"Engleman","year":"2006","journal-title":"Cancer Treat Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"560257","DOI":"10.1155\/2011\/560257","article-title":"Feasibility of treating irradiated bone with intramedullary delivered autologous mesenchymal stem cells","volume":"2011","author":"Phulpin","year":"2011","journal-title":"J. Biomed. Biotechnol."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Sergi, C.M. (2022). Advancements in Cancer Research, Brisbane (AU) Exon Publications.","DOI":"10.36255\/advancements-in-cancer-research"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1295","DOI":"10.1152\/physrev.00036.2016","article-title":"Osteoimmunology: The conceptual framework unifying the immune and skeletal systems","volume":"97","author":"Okamoto","year":"2017","journal-title":"Physiol Rev."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1177\/154405910608500703","article-title":"Bone remodeling in post-menopausal osteoporosis","volume":"85","author":"Lerner","year":"2006","journal-title":"J. Dent. Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1111\/j.1600-0757.2011.00400.x","article-title":"Decreased bone mineral density and periodontal management","volume":"61","author":"Reddy","year":"2013","journal-title":"Periodontol. 2000."},{"key":"ref_30","first-page":"23","article-title":"Bone mass of mandibles. In vitro and in vivo analyses","volume":"33","year":"1986","journal-title":"Dan. Med. Bull."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1137","DOI":"10.1002\/jbmr.5650090802","article-title":"The diagnosis of osteoporosis","volume":"9","author":"Kanis","year":"1994","journal-title":"J. Bone Miner. Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"95","DOI":"10.2147\/CCIDE.S92774","article-title":"Alveolar bone loss in osteoporosis: A loaded and cellular affair?","volume":"8","author":"Jonasson","year":"2016","journal-title":"Clin. Cosmet. Investig. Dent."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1243","DOI":"10.1002\/ar.a.20396","article-title":"Remodeling dynamics in the alveolar process in skeletally mature dogs","volume":"288","author":"Huja","year":"2006","journal-title":"Anat. Rec. Discov. Mol. Cell Evol Biol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2397","DOI":"10.1016\/j.joms.2007.08.003","article-title":"Oral bisphosphonate-induced osteonecrosis: Risk factors, prediction of risk using serum CTX testing, prevention, and treatment","volume":"65","author":"Marx","year":"2007","journal-title":"J. Oral Maxillofac. Surg."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1016\/j.semradonc.2017.04.001","article-title":"Mechanisms of normal tissue injury from irradiation","volume":"27","author":"Citrin","year":"2017","journal-title":"Semin. Radiat. Oncol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/S0167-8140(02)00325-0","article-title":"Partial volume rat lung irradiation; assessment of early DNA damage in different lung regions and effect of radical scavengers","volume":"66","author":"Khan","year":"2003","journal-title":"Radiother. Oncol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"4135","DOI":"10.3892\/mmr.2016.5090","article-title":"Effects of NOX1 on fibroblastic changes of endothelial cells in radiation-induced pulmonary fibrosis","volume":"13","author":"Choi","year":"2016","journal-title":"Mol. Med. Rep."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"5299","DOI":"10.1021\/bi00695a011","article-title":"The interaction of bovine erythrocyte superoxide dismutase with hydrogen peroxide: Chemiluminescence and peroxidation","volume":"14","author":"Hodgson","year":"1975","journal-title":"Biochemistry"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"3029","DOI":"10.1021\/acs.chemrev.5b00407","article-title":"Superoxide Ion: Generation and Chemical Implications","volume":"116","author":"Hayyan","year":"2016","journal-title":"Chem. Rev."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/S0360-3016(00)00435-1","article-title":"TGF-beta1 and radiation fibrosis: A master switch and a specific therapeutic target?","volume":"47","author":"Martin","year":"2000","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1016\/j.joms.2015.07.009","article-title":"Histopathologic and histomorphometric analysis of irradiation injury in bone and the surrounding soft tissues of the jaws","volume":"74","author":"Curi","year":"2016","journal-title":"J. Oral Maxillofac. Surg."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.radonc.2004.08.021","article-title":"The radiation-induced fibroatrophic process: Therapeutic perspective via the antioxidant pathway","volume":"73","author":"Delanian","year":"2004","journal-title":"Radiother. Oncol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1016\/j.bone.2018.12.006","article-title":"Potential role of senescence in radiation-induced damage of the aged skeleton","volume":"120","author":"Chandra","year":"2019","journal-title":"Bone"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"3212","DOI":"10.1089\/ten.tea.2013.0663","article-title":"Total body irradiation is permissive for mesenchymal stem cell-mediated new bone formation following local transplantation","volume":"20","author":"Herberg","year":"2013","journal-title":"Tissue Eng. Part A"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/s13018-015-0339-9","article-title":"Bone marrow stem cell dysfunction in radiation-induced abscopal bone loss","volume":"1","author":"Zou","year":"2016","journal-title":"J. Orthop. Surg. Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1002\/jbmr.1505","article-title":"Devastation of adult stem cell pools by irradiation precedes collapse of trabecular bone quality and quantity","volume":"27","author":"Green","year":"2012","journal-title":"J. Bone Miner. Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1016\/j.bbmt.2017.11.007","article-title":"Mesenchymal stromal cell irradiation interferes with the adipogenic\/osteogenic differentiation balance and improves their hematopoietic-supporting ability","volume":"24","author":"Preciado","year":"2018","journal-title":"Biol. Blood Marrow Transplant."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1478","DOI":"10.1002\/cre2.662","article-title":"Dental management before radiotherapy of the head and neck region: 4-year single-center experience","volume":"8","author":"Hoffmann","year":"2022","journal-title":"Clin. Exp. Dent. Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1016\/0030-4220(87)90136-8","article-title":"Studies in the radiobiology of osteoradionecrosis and their clinical significance","volume":"64","author":"Marx","year":"1987","journal-title":"Oral Surg. Oral Med. Oral Pathol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1016\/j.cmet.2013.06.016","article-title":"Fibrosis and adipose tissue dysfunction","volume":"18","author":"Sun","year":"2013","journal-title":"Cell Metab."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1667\/RR1816.1","article-title":"Hypoxia inducible factor 1alpha signaling in fractionated radiation-induced lung injury: Role of oxidative stress and tissue hypoxia","volume":"73","author":"Rabbani","year":"2010","journal-title":"Radiat. Res."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1016\/S0360-3016(01)01593-0","article-title":"Radiation-induced hypoxia may perpetuate late normal tissue injury","volume":"50","author":"Vujaskovic","year":"2001","journal-title":"Int. J. Radiat. Oncol Biol. Phys."},{"key":"ref_53","first-page":"1077","article-title":"Redox-mediated activation of latent transforming growth factor-beta 1","volume":"10","author":"Dix","year":"1996","journal-title":"Mol. Endocrinol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1101\/gad.14.2.163","article-title":"Cell surface-localized matrix metalloproteinase-9 proteolytically activates TGF-beta and promotes tumor invasion and angiogenesis","volume":"14","author":"Yu","year":"2000","journal-title":"Genes Dev."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.1016\/S0360-3016(00)00482-X","article-title":"Dose-dependent induction of transforming growth factor beta (TGF-beta) in the lung tissue of fibrosis-prone mice after thoracic irradiation","volume":"47","author":"Rube","year":"2000","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.mrfmmm.2010.01.011","article-title":"Medium-mediated DNA repair response after ionizing radiation is correlated with the increase of specific cytokines in human fibroblasts","volume":"687","author":"Dieriks","year":"2010","journal-title":"Mutat. Res."},{"key":"ref_57","first-page":"re5","article-title":"New tricks for an old fox: Impact of TGF\u03b2 on the DNA damage response and genomic stability","volume":"7","author":"Cucinotta","year":"2014","journal-title":"Signal Sci."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1016\/j.bjoms.2008.04.006","article-title":"Osteoradionecrosis of the jaws: Current understanding of its pathophysiology and treatment","volume":"46","author":"Lyons","year":"2008","journal-title":"Br. J. Oral Maxillofac. Surg."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1016\/0196-0709(90)90084-9","article-title":"Osteoradionecrosis of the mandible: Pathogenesis","volume":"11","author":"Bras","year":"1990","journal-title":"Am. J. Otolaryngol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"794","DOI":"10.1002\/hed.26065","article-title":"Post implantation radiation therapy in head and neck cancer patients: Literature review","volume":"42","author":"Koudougou","year":"2020","journal-title":"Head Neck."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"7085","DOI":"10.1038\/sj.onc.1204903","article-title":"Inflammation-type responses after exposure to ionizing radiation in vivo: A mechanism for radiation-induced bystander effects?","volume":"20","author":"Lorimore","year":"2001","journal-title":"Oncogene"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1667\/RR1388.1","article-title":"Early increase in osteoclast number in mice after whole-body irradiation with 2 Gy X rays","volume":"170","author":"Willey","year":"2008","journal-title":"Radiat. Res."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1177\/0022034512448661","article-title":"Early-stage pathogenic sequence of jaw osteoradionecrosis in vivo","volume":"91","author":"Xu","year":"2012","journal-title":"J. Dent. Res."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1016\/j.oraloncology.2018.10.030","article-title":"The irradiated human mandible: A quantitative study on bone vascularity","volume":"87","author":"Dekker","year":"2018","journal-title":"Oral Oncol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"5579","DOI":"10.1007\/s00784-021-04065-6","article-title":"Survival of dental implants and occurrence of osteoradionecrosis in irradiated head and neck cancer patients: A systematic review and meta-analysis","volume":"25","author":"Toneatti","year":"2021","journal-title":"Clin. Oral Investig."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"967","DOI":"10.1111\/clr.13976","article-title":"Dental implants in patients with head and neck cancer-A systematic review and meta-analysis of the influence of radiotherapy on implant survival","volume":"33","author":"Schiegnitz","year":"2022","journal-title":"Clin. Oral Implant Res."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1053\/joms.2001.20998","article-title":"A histomorphometric study of the tissue reaction around hydroxyapatite implants irradiated after placement","volume":"59","author":"Kudo","year":"2001","journal-title":"J. Oral Maxillofac. Surg."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"2575","DOI":"10.1007\/s00405-023-07864-7","article-title":"Pre-chemoradiotherapy low hemoglobin levels indicate increased osteoradionecrosis risk in locally advanced nasopharyngeal cancer patients","volume":"280","author":"Yilmaz","year":"2023","journal-title":"Eur. Arch. Otorhinolaryngol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1695","DOI":"10.1002\/hed.24505","article-title":"Comparison of the incidence of osteoradionecrosis with conventional radiotherapy and intensity-modulated radiotherapy","volume":"38","author":"Maesschalck","year":"2016","journal-title":"Head Neck"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1016\/j.oraloncology.2017.07.014","article-title":"Incidence of and risk factors for mandibular osteoradionecrosis in patients with oral cavity and oropharynx cancers","volume":"72","author":"Moon","year":"2017","journal-title":"Oral Oncol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1007\/s00066-021-01896-w","article-title":"Dental extraction, intensity-modulated radiotherapy of head and neck cancer, and osteoradionecrosis: A systematic review and meta-analysis","volume":"98","author":"Balermpas","year":"2022","journal-title":"Strahlenther. Onkol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1016\/j.radonc.2017.05.006","article-title":"Intensity-modulated proton therapy and osteoradionecrosis in oropharyngeal cancer","volume":"123","author":"Zhang","year":"2017","journal-title":"Radiother. Oncol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/j.radonc.2021.06.022","article-title":"Clinical features and dosimetric evaluation of carbon ion radiation-induced osteoradionecrosis of mandible in head and neck tumors","volume":"61","author":"Musha","year":"2021","journal-title":"Radiother. Oncol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13014-020-01701-5","article-title":"Risk factors for osteoradionecrosis of the jaw in patients with head and neck squamous cell carcinoma","volume":"16","author":"Kubota","year":"2021","journal-title":"Radiat. Oncol."},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"MD Anderson Head and Neck Cancer Symptom Working Group (2017). Dose-volume correlates of mandibular osteoradionecrosis in oropharynx cancer patients receiving intensity-modulated radiotherapy: Results from a case-matched comparison. Radiother. Oncol., 124, 232\u2013239.","DOI":"10.1016\/j.radonc.2017.06.026"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.oooo.2016.01.007","article-title":"Osteoradionecrosis following treatment for head and neck cancer and the effect of radiotherapy dosimetry: The Guy\u2019s and St Thomas\u2019 Head and Neck Cancer Unit experience","volume":"122","author":"Thomas","year":"2016","journal-title":"Oral Surg. Oral Med. Oral Pathol. Oral Radiol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1016\/j.ijrobp.2021.04.042","article-title":"Normal Tissue Complication Probability (NTCP) prediction model for osteoradionecrosis of the mandible in patients with head and neck cancer after radiation therapy: Large-scale observational cohort","volume":"111","author":"Abusaif","year":"2021","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1016\/j.ijrobp.2012.05.032","article-title":"Osteoradionecrosis and radiation dose to the mandible in patients with oropharyngeal cancer","volume":"85","author":"Tsai","year":"2013","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1186\/s13005-022-00311-8","article-title":"Frequency of osteoradionecrosis of the lower jaw after radiotherapy of oral cancer patients correlated with dosimetric parameters and other risk factors","volume":"18","author":"Lang","year":"2022","journal-title":"Head Face Med."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1557","DOI":"10.1016\/j.joms.2022.04.009","article-title":"Is dose volume a better predictor of osteoradionecrosis risk than total dose for patients who have received head and neck radiation?","volume":"80","author":"DeLuke","year":"2022","journal-title":"J. Oral Maxillofac. Surg."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"854","DOI":"10.1016\/j.bjoms.2015.07.008","article-title":"Longitudinal evaluation of health-related quality of life after osteoradionecrosis of the mandible","volume":"53","author":"Rogers","year":"2015","journal-title":"Br. J. Oral Maxillofac Surg."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"e276","DOI":"10.1016\/j.bjoms.2020.07.031","article-title":"Preoperative status and treatment of osteoradionecrosis of the jaw: A retrospective study of 252 cases","volume":"58","author":"Jin","year":"2020","journal-title":"Br. J. Oral Maxillofac. Surg."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1002\/hed.10171","article-title":"Management of mandibular osteoradionecrosis corresponding to the severity of osteoradionecrosis and the method of radiotherapy","volume":"25","author":"Notani","year":"2003","journal-title":"Head Neck"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.1016\/j.ijom.2013.03.022","article-title":"Quality of life after management of advanced osteoradionecrosis of the mandible","volume":"42","author":"Jacobson","year":"2013","journal-title":"Int. J. Oral Maxillofac. Surg."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.1016\/j.bjoms.2021.02.011","article-title":"Health related quality of life and patient concerns in patients with osteoradionecrosis","volume":"59","author":"Chieng","year":"2021","journal-title":"Br. J. Oral Maxillofac. Surg."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1457","DOI":"10.1097\/00000539-200006000-00044","article-title":"Jaw thrust maneuver for endotracheal intubation using a fiberoptic stylet","volume":"90","author":"Aoyama","year":"2000","journal-title":"Anesth. Analg."},{"key":"ref_87","first-page":"90","article-title":"Letter to the Editor: To extract or not extract teeth prior to head and neck radiotherapy?","volume":"28","author":"Yilmaz","year":"2022","journal-title":"Support Care Cancer"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.joms.2022.08.023","article-title":"RE: Is dose volume a better predictor of osteoradionecrosis risk than total dose for patients who have received head and neck radiation?","volume":"81","author":"Topkan","year":"2023","journal-title":"J. Oral Maxillofac. Surg."},{"key":"ref_89","unstructured":"Topkan, E., Somay, E., and Yilmaz, B. (2022). In reply to Shih YJ et.al. (doi: 10.1111\/odi.14349). Oral. Dis."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1038\/s41415-022-4401-9","article-title":"Further analysis desirable","volume":"232","author":"Topkan","year":"2022","journal-title":"Br. Dent. J."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"106098","DOI":"10.1016\/j.oraloncology.2022.106098","article-title":"Comment on: Osteoradionecrosis after postoperative radiotherapy for oral cavity cancer: A retrospective cohort study","volume":"134","author":"Topkan","year":"2022","journal-title":"Oral Oncol."},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Topkan, E., Somay, E., and Yilmaz, B. (2022). In regard to recent published study of Lombardi et al. titled \u2018Pentoxifylline and tocopherol for prevention of osteoradionecrosis in patients who underwent oral surgery: A clinical audit\u2019. (Spec Care Dentist. 2022;10.1111\/scd.12759. https:\/\/doi.org\/10.1111\/scd.12759). Spec. Care Dentist.","DOI":"10.1111\/scd.12778"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1016\/j.ajoms.2014.03.010","article-title":"Incidence of osteoradionecrosis in patients who have undergone dental extraction prior to radiotherapy: A systematic review and meta-analysis","volume":"26","author":"Jiang","year":"2014","journal-title":"J. Oral Maxillofac. Surg. Med. Pathol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.tripleo.2011.07.042","article-title":"Risk factors for osteoradionecrosis after head and neck radiation: A systematic review","volume":"113","author":"Nabil","year":"2012","journal-title":"Oral Surg. Oral Med. Oral Pathol. Oral Radiol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/0360-3016(91)90171-Y","article-title":"Tolerance of normal tissue to therapeutic irradiation","volume":"21","author":"Emami","year":"1990","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1148\/119.3.665","article-title":"Osteonecrosis in patients treated with definitive radiotherapy for squamous cell carcinomas of the oral cavity and naso-and oropharynx","volume":"119","author":"Bedwinek","year":"1976","journal-title":"Radiology"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/S0140-6736(18)32779-X","article-title":"Radiotherapy plus cetuximab or cisplatin in human papillomavirus-positive oropharyngeal cancer (NRG Oncology RTOG 1016): A randomised, multicentre, non-inferiority trial","volume":"393","author":"Gillison","year":"2019","journal-title":"Lancet"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1016\/S1470-2045(11)70303-5","article-title":"Addition of bevacizumab to standard chemoradiation for locoregionally advanced nasopharyngeal carcinoma (RTOG 0615): A phase 2 multi-institutional trial","volume":"13","author":"Lee","year":"2012","journal-title":"Lancet Oncol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1016\/0360-3016(80)90380-6","article-title":"Radiation necrosis of the mandible: A 10-year study. Part I. Factors influencing the onset of necrosis","volume":"6","author":"Murray","year":"1980","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1054\/ijom.2002.0332","article-title":"Osteoradionecrosis of the jaws as a side effect of radiotherapy of head and neck tumour patients-a report of a thirty-year retrospective review","volume":"32","author":"Reuther","year":"2003","journal-title":"Int. J. Oral Maxillofac. Surg."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/12\/8\/3025\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:20:35Z","timestamp":1760124035000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/12\/8\/3025"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4,21]]},"references-count":100,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2023,4]]}},"alternative-id":["jcm12083025"],"URL":"https:\/\/doi.org\/10.3390\/jcm12083025","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,4,21]]}}}