{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T22:49:53Z","timestamp":1785797393021,"version":"3.56.0"},"reference-count":41,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2024,1,17]],"date-time":"2024-01-17T00:00:00Z","timestamp":1705449600000},"content-version":"vor","delay-in-days":85,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,11,1]]},"abstract":"<jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>To identify clinical and local radiographic predictors for medication-related osteonecrosis of the jaws (MRONJ) by the assessment of pre-operative CBCT images of oncologic patients treated with anti-resorptive drugs (ARDs) undergoing tooth extractions.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>This retrospective, longitudinal, case\u2013control study included clinical and imaging data of 97 patients, divided into study and control group. Patients in the study group (n = 47; 87 tooth extractions) had received at least one dose of ARD, undergone tooth extraction(s), and had a pre-operative CBCT. An age-, gender-, and tooth extraction-matched control group (n = 50; 106 tooth extractions) was selected. Three calibrated, blinded, and independent examiners evaluated each tooth extraction site. Statistical analysis used \u03c72\/Fisher\u2019s exact\/Mann\u2013Whitney U test to contrast control and study group, ARD type used, and sites with or without MRONJ development. p-value \u2264 0.05 was considered significant.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>From the study group, 15 patients (32%) and 33 sites (38%) developed MRONJ after tooth extraction. When controls were compared to study sites, the latter showed significantly more thickening of the lamina dura, widened periodontal ligament space, osteosclerosis, osteolysis, and sequestrum formation. In the study group, MRONJ risk significantly increased in patients who had multiple tooth extractions, were smokers, and had shorter drug holidays. Periosteal reaction and sequestrum formation may indicate latent MRONJ lesions. Additionally, patients given bisphosphonates showed considerably more osteosclerosis than those given denosumab.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Periosteal reaction and sequestrum formation are suspected to be pre-clinical MRONJ lesions. Furthermore, ARD induced bony changes and radiographic variations between ARD types were seen.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1259\/dmfr.20230238","type":"journal-article","created":{"date-parts":[[2023,10,24]],"date-time":"2023-10-24T12:38:41Z","timestamp":1698151121000},"source":"Crossref","is-referenced-by-count":10,"title":["Three-dimensional clinical assessment for MRONJ risk in oncologic patients following tooth extractions"],"prefix":"10.1093","volume":"52","author":[{"given":"Catalina","family":"Moreno Rabie","sequence":"first","affiliation":[{"name":"OMFS-IMPATH Research Group, Department of Imaging and Pathology, Faculty of Medicine, University of Leuven , Leuven, Belgium"},{"name":"Department of Oral and Maxillofacial Surgery, University Hospitals Leuven , Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rocharles","family":"Cavalcante Fontenele","sequence":"additional","affiliation":[{"name":"OMFS-IMPATH Research Group, Department of Imaging and Pathology, Faculty of Medicine, University of Leuven , Leuven, Belgium"},{"name":"Department of Oral and Maxillofacial Surgery, University Hospitals Leuven , Leuven, Belgium"},{"name":"Department of Oral Diagnosis, Division of Oral Radiology, Piracicaba Dental School, University of Campinas , Piracicaba, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolly","family":"Oliveira Santos","sequence":"additional","affiliation":[{"name":"OMFS-IMPATH Research Group, Department of Imaging and Pathology, Faculty of Medicine, University of Leuven , Leuven, Belgium"},{"name":"Department of Oral and Maxillofacial Surgery, University Hospitals Leuven , Leuven, Belgium"},{"name":"Department of Oral Diagnosis, Division of Oral Radiology, Piracicaba Dental School, University of Campinas , Piracicaba, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernanda","family":"Nogueira Reis","sequence":"additional","affiliation":[{"name":"OMFS-IMPATH Research Group, Department of Imaging and Pathology, Faculty of Medicine, University of Leuven , Leuven, Belgium"},{"name":"Department of Oral and Maxillofacial Surgery, University Hospitals Leuven , Leuven, Belgium"},{"name":"Department of Oral Diagnosis, Division of Oral Radiology, Piracicaba Dental School, University of Campinas , Piracicaba, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tim","family":"Van den Wyngaert","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, Antwerp University Hospital , Edegem, Belgium"},{"name":"Faculty of Medicine and Health Sciences, University of Antwerp , Antwerp, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reinhilde","family":"Jacobs","sequence":"additional","affiliation":[{"name":"OMFS-IMPATH Research Group, Department of Imaging and Pathology, Faculty of Medicine, University of Leuven , Leuven, Belgium"},{"name":"Department of Oral and Maxillofacial Surgery, University Hospitals Leuven , Leuven, Belgium"},{"name":"Department of Dental Medicine, Karolinska Institutet , Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,10,24]]},"reference":[{"key":"2024011814550562800_b1","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1053\/ctrv.2000.0210","article-title":"Metastatic bone disease: clinical features, pathophysiology and treatment strategies","volume":"27","author":"Coleman","year":"2001","journal-title":"Cancer Treat Rev"},{"key":"2024011814550562800_b2","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1016\/j.ctrv.2015.04.007","article-title":"Drug induced Osteonecrosis of the jaw","volume":"41","author":"Hamadeh","year":"2015","journal-title":"Cancer Treat Rev"},{"key":"2024011814550562800_b3","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1016\/j.bone.2010.11.020","article-title":"Denosumab and Bisphosphonates: different mechanisms of action and effects","volume":"48","author":"Baron","year":"2011","journal-title":"Bone"},{"key":"2024011814550562800_b4","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.bone.2011.04.022","article-title":"Bisphosphonates: the first 40 years","volume":"49","author":"Russell","year":"2011","journal-title":"Bone"},{"key":"2024011814550562800_b5","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1006\/bbrc.1999.1499","article-title":"Farnesyl pyrophosphate synthase is the molecular target of nitrogen-containing Bisphosphonates","volume":"264","author":"van Beek","year":"1999","journal-title":"Biochem Biophys Res Commun"},{"key":"2024011814550562800_b6","doi-asserted-by":"crossref","first-page":"1115","DOI":"10.1016\/S0278-2391(03)00720-1","article-title":"Pamidronate (Aredia) and Zoledronate (Zometa) induced Avascular necrosis of the jaws: a growing epidemic","volume":"61","author":"Marx","year":"2003","journal-title":"J Oral Maxillofac Surg"},{"key":"2024011814550562800_b7","doi-asserted-by":"crossref","first-page":"920","DOI":"10.1016\/j.joms.2022.02.008","article-title":"American Association of oral and Maxillofacial Surgeons' position paper on medication-related Osteonecrosis of the Jaws-2022 update","volume":"80","author":"Ruggiero","year":"2022","journal-title":"J Oral Maxillofac Surg"},{"key":"2024011814550562800_b8","doi-asserted-by":"crossref","DOI":"10.1259\/dmfr.20200417","article-title":"Do various imaging modalities provide potential early detection and diagnosis of medication-related Osteonecrosis of the jaw? A review","volume":"50","author":"Wongratwanich","year":"2021","journal-title":"Dentomaxillofac Radiol"},{"key":"2024011814550562800_b9","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1016\/j.joms.2013.09.008","article-title":"Stage 0 Osteonecrosis of the jaw in a patient on Denosumab","volume":"72","author":"Aghaloo","year":"2014","journal-title":"J Oral Maxillofac Surg"},{"key":"2024011814550562800_b10","doi-asserted-by":"crossref","first-page":"2973","DOI":"10.1007\/s00784-020-03423-0","article-title":"Early imaging signs of the use of Antiresorptive medication and MRONJ: a systematic review","volume":"24","author":"Moreno-Rabi\u00e9","year":"2020","journal-title":"Clin Oral Investig"},{"key":"2024011814550562800_b11","doi-asserted-by":"crossref","DOI":"10.5037\/jomr.2010.1203","article-title":"Bisphosphonate-related Osteonecrosis of the jaw bone: radiological pattern and the potential role of CBCT in early diagnosis","volume":"1","author":"Olutayo","year":"2010","journal-title":"J Oral Maxillofac Res"},{"key":"2024011814550562800_b12","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.1111\/odi.14048","article-title":"Diagnostic accuracy comparing OPT and CBCT in the detection of Non-Vital bone changes before tooth Extractions in patients with Antiresorptive intake","volume":"29","author":"Ristow","year":"2023","journal-title":"Oral Dis"},{"key":"2024011814550562800_b13","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1159\/000151451","article-title":"Bisphosphonate-related Osteonecrosis of the jaw: model and diagnosis with cone beam computerized tomography","volume":"189","author":"Barragan-Adjemian","year":"2009","journal-title":"Cells Tissues Organs"},{"key":"2024011814550562800_b14","doi-asserted-by":"crossref","first-page":"826","DOI":"10.1359\/jbmr.080205","article-title":"Frequency and risk factors associated with Osteonecrosis of the jaw in cancer patients treated with intravenous Bisphosphonates","volume":"23","author":"Hoff","year":"2008","journal-title":"J Bone Miner Res"},{"key":"2024011814550562800_b15","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1016\/j.bjoms.2009.08.030","article-title":"Osteonecrosis of the jaws induced by anti-RANK ligand therapy","volume":"48","author":"Taylor","year":"2010","journal-title":"Br J Oral Maxillofac Surg"},{"key":"2024011814550562800_b16","doi-asserted-by":"crossref","DOI":"10.1111\/odi.14496","article-title":"Local radiographic risk factors for MRONJ in Osteoporotic patients undergoing tooth extraction","author":"Moreno-Rabi\u00e9","year":"2023","journal-title":"Oral Dis"},{"key":"2024011814550562800_b17","doi-asserted-by":"crossref","DOI":"10.1038\/s41598-022-15254-y","article-title":"Radiographic predictors for MRONJ in oncologic patients undergoing tooth extraction","volume":"12","author":"Moreno-Rabi\u00e9","year":"2022","journal-title":"Sci Rep"},{"key":"2024011814550562800_b18","first-page":"87","article-title":"Why do some extraction sites develop medication-related Osteonecrosis of the jaw and others do not? A within-patient study assessing radiographic predictors","volume":"14","author":"Ga\u00eata-Araujo","year":"2021","journal-title":"Int J Oral Implantol (Berl)"},{"key":"2024011814550562800_b19","doi-asserted-by":"crossref","first-page":"1500","DOI":"10.1016\/j.ijsu.2014.07.014","article-title":"Strengthening the reporting of observational studies in epidemiology (STROBE): explanation and elaboration","volume":"12","author":"Vandenbroucke","year":"2014","journal-title":"Int J Surg"},{"key":"2024011814550562800_b20","unstructured":"Center for Disease Control and Prevention. NHIS - Adult Tobacco Use - Glossary\n          \n.\nAdult Tobacco use Information\n\u00a02017\n.\nAvailable from\n:\nhttps:\/\/www.cdc.gov\/nchs\/nhis\/tobacco\/tobacco_glossary.htm\n(\naccessed\n\u00a013 Jul 2023\n)"},{"key":"2024011814550562800_b21","doi-asserted-by":"crossref","first-page":"1410","DOI":"10.1111\/iej.13158","article-title":"Root canal configuration and its relation with Endodontic technical errors in Premolar teeth: a CBCT analysis","volume":"52","author":"Nascimento","year":"2019","journal-title":"Int Endod J"},{"key":"2024011814550562800_b22","doi-asserted-by":"crossref","DOI":"10.5395\/rde.2021.46.e43","article-title":"Which factors related to apical Radiolucency may influence its radiographic detection? A study using CBCT as reference standard","volume":"46","author":"Fontenele","year":"2021","journal-title":"Restor Dent Endod"},{"key":"2024011814550562800_b23","doi-asserted-by":"crossref","DOI":"10.1259\/dmfr.20180128","article-title":"Medication related Osteonecrosis of the jaw in Osteoporotic vs oncologic patients\u2014Quantifying radiographic appearance and relationship to clinical findings","volume":"48","author":"Walton","year":"2019","journal-title":"Dentomaxillofac Radiol"},{"key":"2024011814550562800_b24","doi-asserted-by":"crossref","first-page":"3193","DOI":"10.1007\/s00784-019-03193-4","article-title":"A new cone-beam computed tomography-driven index for osteoporosis prediction","volume":"24","author":"de Castro","year":"2020","journal-title":"Clin Oral Investig"},{"key":"2024011814550562800_b25","first-page":"360","article-title":"Understanding Interobserver agreement: the Kappa Statistic","volume":"37","author":"Viera","year":"2005","journal-title":"Fam Med"},{"key":"2024011814550562800_b26","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1016\/j.tripleo.2009.12.005","article-title":"Use of cone-beam computerized tomography for evaluation of Bisphosphonate-associated Osteonecrosis of the jaws","volume":"109","author":"Treister","year":"2010","journal-title":"Oral Surg Oral Med Oral Pathol Oral Radiol Endod"},{"key":"2024011814550562800_b27","doi-asserted-by":"crossref","first-page":"2232","DOI":"10.1016\/j.joms.2010.05.003","article-title":"Radiographic findings in Bisphosphonate-treated patients with stage 0 disease in the absence of bone exposure","volume":"68","author":"Hutchinson","year":"2010","journal-title":"J Oral Maxillofac Surg"},{"key":"2024011814550562800_b28","doi-asserted-by":"crossref","DOI":"10.1259\/dmfr.20160065","article-title":"Can dental panoramic radiographic findings serve as indicators for the development of medication-related Osteonecrosis of the jaw","volume":"45","author":"Klingelh\u00f6ffer","year":"2016","journal-title":"Dentomaxillofac Radiol"},{"key":"2024011814550562800_b29","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/8756-3282(95)00445-9","article-title":"Bisphosphonates: A review of their pharmacokinetic properties","volume":"18","author":"Lin","year":"1996","journal-title":"Bone"},{"key":"2024011814550562800_b30","doi-asserted-by":"crossref","first-page":"247","DOI":"10.2165\/11598090-000000000-00000","article-title":"Population pharmacokinetic analysis of Denosumab in patients with bone metastases from solid tumours","volume":"51","author":"Gibiansky","year":"2012","journal-title":"Clin Pharmacokinet"},{"key":"2024011814550562800_b31","doi-asserted-by":"crossref","first-page":"4171","DOI":"10.1007\/s00520-021-06129-5","article-title":"Differences between Bisphosphonate-related and Denosumab-related Osteonecrosis of the jaws: a systematic review","volume":"29","author":"Querrer","year":"2021","journal-title":"Support Care Cancer"},{"key":"2024011814550562800_b32","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1016\/j.oooo.2019.09.010","article-title":"A comparison of the cone beam computed tomography findings in medication-related Osteonecrosis of the jaws related to Denosumab versus Bisphosphonates: an observational pilot study","volume":"129","author":"Pichardo","year":"2020","journal-title":"Oral Surg Oral Med Oral Pathol Oral Radiol"},{"key":"2024011814550562800_b33","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1016\/j.coms.2015.06.001","article-title":"Pathophysiology of Osteonecrosis of the jaws","volume":"27","author":"Aghaloo","year":"2015","journal-title":"Oral Maxillofac Surg Clin North Am"},{"key":"2024011814550562800_b34","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.bjoms.2014.09.001","article-title":"Up to a quarter of patients with Osteonecrosis of the jaw associated with Antiresorptive agents remain Undiagnosed","volume":"53","author":"Fedele","year":"2015","journal-title":"Br J Oral Maxillofac Surg"},{"key":"2024011814550562800_b35","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1016\/j.bjoms.2014.04.009","article-title":"Staging of Osteonecrosis of the jaw requires computed tomography for accurate definition of the extent of bony disease","volume":"52","author":"Bedogni","year":"2014","journal-title":"Br J Oral Maxillofac Surg"},{"key":"2024011814550562800_b36","doi-asserted-by":"crossref","first-page":"922","DOI":"10.1111\/jcpe.12455","article-title":"Occurrence and risk indicators of medication-related Osteonecrosis of the jaw after dental extraction: a systematic review and meta-analysis","volume":"42","author":"Gaudin","year":"2015","journal-title":"J Clin Periodontol"},{"key":"2024011814550562800_b37","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/0030-4220(69)90357-0","article-title":"The time sequence of tissue regeneration in human extraction wounds","volume":"27","author":"Amler","year":"1969","journal-title":"Oral Surg Oral Med Oral Pathol"},{"key":"2024011814550562800_b38","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1111\/prd.12082","article-title":"Alveolar socket healing: what can we learn?","volume":"68","author":"Ara\u00fajo","year":"2015","journal-title":"Periodontol 2000"},{"key":"2024011814550562800_b39","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1016\/j.joms.2009.10.026","article-title":"Occurrence of Bisphosphonate-related Osteonecrosis of the jaw after surgical tooth extraction","volume":"68","author":"Saia","year":"2010","journal-title":"J Oral Maxillofac Surg"},{"key":"2024011814550562800_b40","doi-asserted-by":"crossref","first-page":"406","DOI":"10.14219\/jada.archive.2013.0134","article-title":"Assessing the association between Bisphosphonate exposure and delayed Mucosal healing after tooth extraction","volume":"144","author":"Migliorati","year":"2013","journal-title":"J Am Dent Assoc"},{"key":"2024011814550562800_b41","doi-asserted-by":"crossref","DOI":"10.3390\/jcm12010239","article-title":"Management of tooth extraction in patients taking Antiresorptive drugs: an evidence mapping review and meta-analysis","volume":"12","author":"Liu","year":"2022","journal-title":"J Clin Med"}],"container-title":["Dentomaxillofacial Radiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/dmfr\/article-pdf\/52\/8\/20230238\/56206574\/dmfr.20230238.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/dmfr\/article-pdf\/52\/8\/20230238\/56206574\/dmfr.20230238.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,18]],"date-time":"2024-01-18T14:55:35Z","timestamp":1705589735000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/dmfr\/article\/doi\/10.1259\/dmfr.20230238\/7491447"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,10,24]]},"references-count":41,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2023,11,1]]}},"URL":"https:\/\/doi.org\/10.1259\/dmfr.20230238","relation":{},"ISSN":["0250-832X","1476-542X"],"issn-type":[{"value":"0250-832X","type":"print"},{"value":"1476-542X","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2023,11,1]]},"published":{"date-parts":[[2023,10,24]]},"article-number":"20230238"}}