{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T11:25:08Z","timestamp":1787743508342,"version":"build-2784847793"},"reference-count":24,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T00:00:00Z","timestamp":1787702400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Background\/Objectives: Medication-related osteonecrosis of the jaw (MRONJ) is a known side effect of antiresorptive agents. Although the jawbone has been extensively investigated, histopathological changes in the overlying oral mucosa remain poorly characterized. We previously reported small bone fragments located within the oral mucosa of a patient with MRONJ. This study aimed to investigate the presence and histopathological characteristics of those fragments in other patients with surgically treated MRONJ. Case Presentation: This retrospective case series included six patients with stage 3 mandibular MRONJ who underwent marginal or segmental resection. Archived histological sections from these patients were examined. Oral mucosal specimens had been separated from the underlying osseous lesions for independent histological evaluation. In this study, small intramucosal sequestra were defined as small bone fragments that appeared to be completely surrounded by mucosal connective tissue in individual two-dimensional sections. All sections had been stained with hematoxylin and eosin, and additional von Kossa staining had been performed on oral mucosal sections from five of the six cases. Histopathological evaluation of small intramucosal sequestra included the presence, size range, and association with pseudoepitheliomatous hyperplasia (PEH). Results: Small intramucosal sequestra were identified in all six patients. They were present either singly or in clusters within the connective tissue beneath the oral epithelium. The intramucosal sequestra exhibited empty osteocytic lacunae, indicating devitalized bone, and were positive for von Kossa staining in all five examined cases, confirming their mineralized nature. In two patients, PEH was observed in direct contact with the small sequestra, some of which appeared to be embedded within the advancing epithelial fronts. Conclusions: Small intramucosal sequestra were a recurrent histopathological finding in this selected series of surgically resected stage 3 mandibular MRONJ. Their presence highlights histopathological changes in the oral mucosa overlying necrotic jawbone that have received limited attention. Further studies including broader patient populations and appropriate comparison groups are needed to determine the generalizability and disease specificity of this finding and its potential relevance to MRONJ pathogenesis.<\/jats:p>","DOI":"10.3390\/diagnostics16172731","type":"journal-article","created":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T10:59:23Z","timestamp":1787741963000},"page":"2731","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Small Intramucosal Sequestra in Medication-Related Osteonecrosis of the Jaw: A Case Series"],"prefix":"10.3390","volume":"16","author":[{"given":"Usagi","family":"Hayashi","sequence":"first","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu City 514-8507, Mie, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaku","family":"Koizumi","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu City 514-8507, Mie, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenya","family":"Okumura","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu City 514-8507, Mie, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-8624-6367","authenticated-orcid":false,"given":"Rina","family":"Yamada","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu City 514-8507, Mie, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kokoro","family":"Nagata","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu City 514-8507, Mie, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8859-7854","authenticated-orcid":false,"given":"Kazuto","family":"Kurohara","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu City 514-8507, Mie, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-1741-7335","authenticated-orcid":false,"given":"Taku","family":"Murata","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu City 514-8507, Mie, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6498-9741","authenticated-orcid":false,"given":"Kasumi","family":"Shimizu","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu City 514-8507, Mie, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-5554-9065","authenticated-orcid":false,"given":"Akinobu","family":"Hayashi","sequence":"additional","affiliation":[{"name":"Pathology Division, Mie University Hospital, 2-174 Edobashi, Tsu City 514-8507, Mie, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3055-5202","authenticated-orcid":false,"given":"Keiichi","family":"Yamanaka","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu City 514-8507, Mie, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-0819-4900","authenticated-orcid":false,"given":"Naoya","family":"Arai","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu City 514-8507, Mie, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,26]]},"reference":[{"key":"ref_1","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. 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