{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T15:38:11Z","timestamp":1773934691647,"version":"3.50.1"},"reference-count":49,"publisher":"Elsevier BV","issue":"3","license":[{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"funder":[{"DOI":"10.13039\/501100002322","name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.jp","jendodon.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Journal of Endodontics"],"published-print":{"date-parts":[[2026,3]]},"DOI":"10.1016\/j.joen.2025.12.002","type":"journal-article","created":{"date-parts":[[2025,12,11]],"date-time":"2025-12-11T08:01:12Z","timestamp":1765440072000},"page":"359-375","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":1,"title":["Untreated Apical Periodontitis and the Risk of Medication-related Osteonecrosis of the Jaws (MRONJ): A Systematic Review with Mechanistic Insights from Preclinical Studies"],"prefix":"10.1016","volume":"52","author":[{"given":"Maria Em\u00edlia","family":"Mota","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nelise Alexandre","family":"Silva Lascane","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thais","family":"Gimenez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"F\u00e1bio Abreu","family":"Alves","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4533-4544","authenticated-orcid":false,"given":"Maria Stella","family":"Moreira","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"78","reference":[{"key":"10.1016\/j.joen.2025.12.002_bib1","doi-asserted-by":"crossref","first-page":"920","DOI":"10.1016\/j.joms.2022.02.008","article-title":"American Association of Oral and Maxillofacial Surgeons\u2019 position paper on medication-related osteonecrosis of the jaws\u20142022 update","volume":"80","author":"Ruggiero","year":"2022","journal-title":"J Oral Maxillofac Sug"},{"key":"10.1016\/j.joen.2025.12.002_bib2","doi-asserted-by":"crossref","first-page":"3679","DOI":"10.1111\/odi.14887","article-title":"Italian position paper SIPMO-SICMF on medication-related osteonecrosis of the jaw (MRONJ)","volume":"30","author":"Bedogni","year":"2024","journal-title":"Oral Dis"},{"key":"10.1016\/j.joen.2025.12.002_bib3","doi-asserted-by":"crossref","first-page":"95","DOI":"10.3390\/biomedicines8040095","article-title":"Does medication-related osteonecrosis of the jaw influence the quality of life of cancer patients?","volume":"8","author":"Tenore","year":"2020","journal-title":"Biomedicines"},{"key":"10.1016\/j.joen.2025.12.002_bib4","doi-asserted-by":"crossref","first-page":"712","DOI":"10.1111\/iej.13467","article-title":"The global prevalence of apical periodontitis: a systematic review and meta-analysis","volume":"54","author":"Tib\u00farcio-Machado","year":"2021","journal-title":"Int Endod J"},{"key":"10.1016\/j.joen.2025.12.002_bib5","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1111\/iej.12507","article-title":"Endodontic medicine: connections between apical periodontitis and systemic diseases","volume":"48","author":"Segura-Egea","year":"2015","journal-title":"Int Endod J"},{"key":"10.1016\/j.joen.2025.12.002_bib6","doi-asserted-by":"crossref","first-page":"272","DOI":"10.3390\/dj12080272","article-title":"Osteoporosis and apical periodontitis prevalence: a systematic review","volume":"12","author":"Pestana de Vasconcelos","year":"2024","journal-title":"Dent J (Basel)"},{"key":"10.1016\/j.joen.2025.12.002_bib7","doi-asserted-by":"crossref","first-page":"e711","DOI":"10.4317\/medoral.26697","article-title":"Apical periodontitis in osteoporotic postmenopausal women: systematic review and meta-analysis","volume":"29","author":"Areal-Quecuty","year":"2024","journal-title":"Med Oral Patol Oral Cir Bucal"},{"key":"10.1016\/j.joen.2025.12.002_bib8","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.joen.2024.10.014","article-title":"Endodontic treatment in patients undergoing hematopoietic stem cell transplantation: a retrospective cohort study","volume":"51","author":"Mota","year":"2025","journal-title":"J Endod"},{"key":"10.1016\/j.joen.2025.12.002_bib9","doi-asserted-by":"crossref","first-page":"e383","DOI":"10.4317\/medoral.23416","article-title":"Prevalence of apical periodontitis in patients with multiple myeloma","volume":"25","author":"O\u00f1ate-S\u00e1nchez","year":"2020","journal-title":"Med Oral Patol Oral Cir Bucal"},{"key":"10.1016\/j.joen.2025.12.002_bib10","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1111\/j.1365-2591.2010.01703.x","article-title":"Effect of alendronate on alveolar bone resorption and angiogenesis in rats with experimental periapical lesions","volume":"43","author":"Xiong","year":"2010","journal-title":"Int Endod J"},{"key":"10.1016\/j.joen.2025.12.002_bib11","doi-asserted-by":"crossref","first-page":"1631","DOI":"10.1002\/jbmr.1894","article-title":"Periapical disease and bisphosphonates induce osteonecrosis of the jaws in mice","volume":"28","author":"Kang","year":"2013","journal-title":"J Bone Mineral Res"},{"key":"10.1016\/j.joen.2025.12.002_bib12","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1002\/jbmr.2097","article-title":"RANKL inhibitors induce osteonecrosis of the jaw in mice with periapical disease","volume":"29","author":"Aghaloo","year":"2014","journal-title":"J Bone Mineral Res"},{"key":"10.1016\/j.joen.2025.12.002_bib13","doi-asserted-by":"crossref","first-page":"1641","DOI":"10.1016\/j.joen.2016.07.020","article-title":"Preexisting periapical inflammatory condition exacerbates tooth extraction\u2013induced bisphosphonate-related osteonecrosis of the jaw lesions in mice","volume":"42","author":"Song","year":"2016","journal-title":"J Endod"},{"key":"10.1016\/j.joen.2025.12.002_bib14","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2017\/1560175","article-title":"Role of periapical diseases in medication-related osteonecrosis of the jaws","volume":"2017","author":"Rao","year":"2017","journal-title":"Biomed Res Int"},{"key":"10.1016\/j.joen.2025.12.002_bib15","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1590\/0103-6440201601558","article-title":"Effects of zoledronic acid in experimental periapical lesions in rats: an imaging and histological analysis","volume":"28","author":"Fran\u00e7a","year":"2017","journal-title":"Braz Dent J"},{"key":"10.1016\/j.joen.2025.12.002_bib16","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1016\/j.jcms.2018.08.011","article-title":"Influence of induced infection in medication-related osteonecrosis of the jaw development after tooth extraction: a study in rats","volume":"47","author":"Bolette","year":"2019","journal-title":"J Craniomaxillofac Surg"},{"key":"10.1016\/j.joen.2025.12.002_bib17","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.joms.2018.08.010","article-title":"Development of medication-related osteonecrosis of the jaw after extraction of teeth with experimental periapical disease","volume":"77","author":"Hadaya","year":"2019","journal-title":"J Oral Maxillofac Surg"},{"key":"10.1016\/j.joen.2025.12.002_bib18","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2019\/1271492","article-title":"Effect of periapical diseases in development of MRONJ in immunocompromised mouse model","volume":"2019","author":"Rao","year":"2019","journal-title":"Biomed Res Int"},{"key":"10.1016\/j.joen.2025.12.002_bib19","doi-asserted-by":"crossref","first-page":"168","DOI":"10.3390\/dj11070168","article-title":"The role of apical periodontitis disease in the development of bisphosphonate-related osteonecrosis of the jaw: an animal study","volume":"11","author":"Marques-Ferreira","year":"2023","journal-title":"Dent J (Basel)"},{"key":"10.1016\/j.joen.2025.12.002_bib20","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1016\/j.ajoms.2024.02.006","article-title":"Role of actinomyces in the progression of medication-related osteonecrosis of the jaws in an immunocompromised mouse model with periapical disease","volume":"36","author":"Li","year":"2024","journal-title":"J Oral Maxillofac Surg Med Pathol"},{"key":"10.1016\/j.joen.2025.12.002_bib21","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1111\/odi.12708","article-title":"Risk factors for medication-related osteonecrosis of the jaws: a systematic review","volume":"24","author":"McGowan","year":"2018","journal-title":"Oral Dis"},{"key":"10.1016\/j.joen.2025.12.002_bib22","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1016\/j.oooo.2018.08.015","article-title":"Prevalence, initiating factor, and treatment outcome of medication-related osteonecrosis of the jaw- a 4-year prospective study","volume":"126","author":"Hallmer","year":"2019","journal-title":"Oral Surg Oral Med Oral Pathol Oral Radiol"},{"key":"10.1016\/j.joen.2025.12.002_bib23","doi-asserted-by":"crossref","first-page":"1567","DOI":"10.1016\/j.joms.2005.07.010","article-title":"Bisphosphonate-induced exposed bone (osteonecrosis\/osteopetrosis) of the jaws: risk factors, recognition, prevention and treatment","volume":"63","author":"Marx","year":"2005","journal-title":"J Oral Maxillofac Surg"},{"key":"10.1016\/j.joen.2025.12.002_bib24","doi-asserted-by":"crossref","first-page":"n71","DOI":"10.1136\/bmj.n71","article-title":"The PRISMA 2020 statement: an updated guideline for reporting systematic reviews","volume":"372","author":"Page","year":"2021","journal-title":"BMJ"},{"key":"10.1016\/j.joen.2025.12.002_bib25","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1186\/1471-2288-14-43","article-title":"SYRCLE\u2019s risk of bias tool for animals studies","volume":"26","author":"Hoojimans","year":"2014","journal-title":"BMC MED Res Methodol"},{"key":"10.1016\/j.joen.2025.12.002_bib26","doi-asserted-by":"crossref","first-page":"1341","DOI":"10.1093\/annonc\/mdr435","article-title":"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","volume":"23","author":"Saad","year":"2012","journal-title":"Ann Oncol"},{"key":"10.1016\/j.joen.2025.12.002_bib27","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1016\/j.sdentj.2022.01.003","article-title":"Medication-Related Osteonecrosis of the Jaw (MRONJ): a review of pathophysiology, risk factors, preventive measures and treatment strategies","volume":"34","author":"AlRowis","year":"2022","journal-title":"Saudi Dent J"},{"key":"10.1016\/j.joen.2025.12.002_bib28","doi-asserted-by":"crossref","first-page":"1526","DOI":"10.1111\/iej.14125","article-title":"The immune landscape in apical periodontitis: from mechanism to therapy","volume":"57","author":"Wen","year":"2024","journal-title":"Int Endod J"},{"key":"10.1016\/j.joen.2025.12.002_bib29","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1034\/j.1600-9657.2000.016001001.x","article-title":"Macrophages in periapical lesions","volume":"16","author":"Metzger","year":"2000","journal-title":"Endod Dent Traumatol"},{"key":"10.1016\/j.joen.2025.12.002_bib30","article-title":"Mechanisms of bone remodeling and therapeutic strategies in chronic apical periodontitis","volume":"22","author":"Luo","year":"2022","journal-title":"Front Cell Infect Microbiol"},{"key":"10.1016\/j.joen.2025.12.002_bib31","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1016\/S0022-3565(24)38786-5","article-title":"Structure-activity relationships for inhibition of farnesyl diphosphate synthase in vitro and inhibition of bone resorption in vivo by nitrogen-containing bisphosphonates","volume":"296","author":"Dunford","year":"2001","journal-title":"J Pharmacol Exp Ther"},{"key":"10.1016\/j.joen.2025.12.002_bib32","doi-asserted-by":"crossref","first-page":"534","DOI":"10.1177\/0022034515572021","article-title":"Infection and medication-related osteonecrosis of the jaw","volume":"94","author":"Katsarelis","year":"2015","journal-title":"J Dent Res"},{"key":"10.1016\/j.joen.2025.12.002_bib33","first-page":"1440","article-title":"Osteonecrosis of the jaws caused by bisphosphonate treatment and oxidative stress in mice","volume":"17","author":"Tamaoka","year":"2019","journal-title":"Exp Ther Med"},{"key":"10.1016\/j.joen.2025.12.002_bib34","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1111\/jop.12151","article-title":"Oxidative stress in bisphosphonate-related osteonecrosis of the jaws","volume":"43","author":"Bagan","year":"2014","journal-title":"J Oral Pathol Med"},{"key":"10.1016\/j.joen.2025.12.002_bib35","doi-asserted-by":"crossref","first-page":"2793","DOI":"10.2147\/DDDT.S456811","article-title":"Inflammation can be a high-risk factor for mucosal nonunion of MRONJ by regulating SIT1 signaling when treated with an oncologic dose of zoledronate","volume":"18","author":"Zhu","year":"2024","journal-title":"Drug Des Devel Ther"},{"key":"10.1016\/j.joen.2025.12.002_bib36","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1111\/jop.12963","article-title":"Association between periodontitis and medication-related osteonecrosis of the jaw: a systematic review and meta-analysis","volume":"49","author":"Lorenzo-Pouso","year":"2020","journal-title":"J Oral Pathol Med"},{"key":"10.1016\/j.joen.2025.12.002_bib37","doi-asserted-by":"crossref","first-page":"1871","DOI":"10.1002\/jbmr.379","article-title":"Periodontal disease and bisphosphonates induce osteonecrosis of the jaws in the rat","volume":"26","author":"Aghaloo","year":"2011","journal-title":"J Bone Miner Res"},{"key":"10.1016\/j.joen.2025.12.002_bib38","article-title":"The role of the immune response in the development of medication-related osteonecrosis of the jaw","volume":"25","author":"Zhang","year":"2021","journal-title":"Front Immunol"},{"key":"10.1016\/j.joen.2025.12.002_bib39","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1007\/s00784-014-1219-0","article-title":"In vitro effects of bisphosphonates on chemotaxis, phagocytosis, and oxidative burst of neutrophil granulocytes","volume":"19","author":"Hagelauer","year":"2015","journal-title":"Clin Oral Investig"},{"key":"10.1016\/j.joen.2025.12.002_bib40","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1007\/s10787-015-0233-4","article-title":"Effect of bisphosphonates treatment on cytokine imbalance between TH17 and Treg in osteoporosis","volume":"23","author":"Talaat","year":"2015","journal-title":"Inflammopharmacology"},{"key":"10.1016\/j.joen.2025.12.002_bib41","doi-asserted-by":"crossref","first-page":"2698","DOI":"10.1016\/j.joms.2011.02.065","article-title":"Matrix metalloproteinase-9 expression in alveolar extraction sockets of zoledronic acid-treated rats","volume":"69","author":"Basi","year":"2011","journal-title":"J Oral Maxillofac Surg"},{"key":"10.1016\/j.joen.2025.12.002_bib42","doi-asserted-by":"crossref","first-page":"2705","DOI":"10.2217\/fon-2020-1240","article-title":"Dental pathologies in tumor patients with bone metastases or multiple myeloma scheduled for antiresorptive therapy","volume":"17","author":"Laimer","year":"2021","journal-title":"Future Oncol"},{"key":"10.1016\/j.joen.2025.12.002_bib43","doi-asserted-by":"crossref","first-page":"3383","DOI":"10.3390\/jcm12103383","article-title":"Clinical and histopathological aspects of MRONJ in cancer patients","volume":"12","author":"Ciobanu","year":"2023","journal-title":"J Clin Med"},{"key":"10.1016\/j.joen.2025.12.002_bib44","doi-asserted-by":"crossref","DOI":"10.20396\/bjos.v21i00.8666585","article-title":"A systematic review assessing occurrence of medication-related osteonecrosis of the jaw following dental procedures","volume":"21","author":"Lara","year":"2022","journal-title":"Braz J Oral Sci"},{"key":"10.1016\/j.joen.2025.12.002_bib45","article-title":"Incidence of medication-related osteonecrosis of the jaw and associated antiresorptive drugs in adult Finnish population","volume":"19","author":"Kujanpaa","year":"2025","journal-title":"Sci Rep"},{"key":"10.1016\/j.joen.2025.12.002_bib46","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1111\/aej.12893","article-title":"Peri-implant medication-related osteonecrosis of the jaw mimicking endodontic disease in a cancer patient: a case report","volume":"50","author":"Rocha","year":"2024","journal-title":"Aust Endod J"},{"key":"10.1016\/j.joen.2025.12.002_bib47","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.joms.2009.01.007","article-title":"The pathogenesis of bisphosphonate-related osteonecrosis of the jaw: so many hypotheses, so few data","volume":"67","author":"Allen","year":"2009","journal-title":"J Oral Maxillofac Surg"},{"key":"10.1016\/j.joen.2025.12.002_bib48","doi-asserted-by":"crossref","DOI":"10.1038\/s41598-021-96480-8","article-title":"Relationship between tooth extraction and development of medication-related osteonecrosis of the jaw in cancer patients","volume":"11","author":"Soutome","year":"2021","journal-title":"Sci Rep"},{"key":"10.1016\/j.joen.2025.12.002_bib49","doi-asserted-by":"crossref","first-page":"5356","DOI":"10.1200\/JCO.2009.21.9584","article-title":"Longitudinal cohort study of risk factors in cancer patients of bisphosphonate-related osteonecrosis of the jaw","volume":"27","author":"Vahtsevanos","year":"2009","journal-title":"J Clinc Oncol"}],"container-title":["Journal of Endodontics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0099239925008015?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0099239925008015?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T13:26:42Z","timestamp":1773926802000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0099239925008015"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3]]},"references-count":49,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2026,3]]}},"alternative-id":["S0099239925008015"],"URL":"https:\/\/doi.org\/10.1016\/j.joen.2025.12.002","relation":{},"ISSN":["0099-2399"],"issn-type":[{"value":"0099-2399","type":"print"}],"subject":[],"published":{"date-parts":[[2026,3]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Untreated Apical Periodontitis and the Risk of Medication-related Osteonecrosis of the Jaws (MRONJ): A Systematic Review with Mechanistic Insights from Preclinical Studies","name":"articletitle","label":"Article Title"},{"value":"Journal of Endodontics","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.joen.2025.12.002","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 American Association of Endodontists.","name":"copyright","label":"Copyright"}]}}