{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T14:27:53Z","timestamp":1766068073398,"version":"build-2065373602"},"reference-count":38,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2024,11,12]],"date-time":"2024-11-12T00:00:00Z","timestamp":1731369600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background: Bisphosphonates used for the treatment of osteoporosis, hypercalcemia, or heterotopic calcifications can cause serious adverse dental events such as osteonecrosis of the maxillary and mandibular bones. However, the effects in childhood remain scarcely explored. Case Presentations: We encountered two children who had started bisphosphonate therapy before completion of the primary dentition. No systemic disease causing congenital delayed tooth eruption was diagnosed. Although the children\u2019s height and weight increased with age, their tooth eruption was significantly delayed compared with the mean. The primary teeth gradually erupted in the follow-up period; however, some teeth did not completely erupt and needed to be extracted to allow for permanent tooth eruption. Conclusions: We report a case of children with early use of bisphosphonates and eruption disturbance, highlighting the need for further investigation into the relationship between these factors.<\/jats:p>","DOI":"10.3390\/ph17111521","type":"journal-article","created":{"date-parts":[[2024,11,12]],"date-time":"2024-11-12T05:21:59Z","timestamp":1731388919000},"page":"1521","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Eruption Disturbance in Children Receiving Bisphosphonates: Two Case Reports"],"prefix":"10.3390","volume":"17","author":[{"given":"Tatsuya","family":"Akitomo","sequence":"first","affiliation":[{"name":"Department of Pediatric Dentistry, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8553, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9387-7746","authenticated-orcid":false,"given":"Yuko","family":"Iwamoto","sequence":"additional","affiliation":[{"name":"Department of Pediatric Dentistry, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8553, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mariko","family":"Kametani","sequence":"additional","affiliation":[{"name":"Department of Pediatric Dentistry, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8553, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ami","family":"Kaneki","sequence":"additional","affiliation":[{"name":"Department of Pediatric Dentistry, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8553, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Taku","family":"Nishimura","sequence":"additional","affiliation":[{"name":"Department of Pediatric Dentistry, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8553, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chieko","family":"Mitsuhata","sequence":"additional","affiliation":[{"name":"Department of Pediatric Dentistry, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8553, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryota","family":"Nomura","sequence":"additional","affiliation":[{"name":"Department of Pediatric Dentistry, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8553, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,11,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e076898","DOI":"10.1136\/bmj-2023-076898","article-title":"Bisphosphonates","volume":"386","author":"Billington","year":"2024","journal-title":"BMJ"},{"key":"ref_2","first-page":"111","article-title":"Bisphosphonate-related osteonecrosis of the jaws. A severe side effect of bisphosphonate therapy","volume":"55","year":"2012","journal-title":"Acta Medica"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Ahdi, H.S., Wichelmann, T.A., Pandravada, S., and Ehrenpreis, E.D. (2023). Medication-induced osteonecrosis of the jaw: A review of cases from the Food and Drug Administration Adverse Event Reporting System (FAERS). BMC Pharmacol. Toxicol., 24.","DOI":"10.1186\/s40360-023-00657-y"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1159\/000365889","article-title":"The use of bisphosphonates in pediatrics","volume":"82","author":"Baroncelli","year":"2014","journal-title":"Horm. Res. Paediatr."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.jdsr.2022.03.001","article-title":"Management of bisphosphonate preparation-treated children in the field of pediatric dentistry","volume":"58","author":"Mitsuhata","year":"2022","journal-title":"Jpn. Dent. Sci. Rev."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1007\/s00223-021-00835-2","article-title":"Abnormalities in Tooth Formation after Early Bisphosphonate Treatment in Children with Osteogenesis Imperfecta","volume":"109","author":"Malmgren","year":"2021","journal-title":"Calcif. Tissue Int."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1016\/j.bone.2014.08.018","article-title":"Preclinical evidence of potential craniofacial adverse effect of zoledronic acid in pediatric patients with bone malignancies","volume":"68","author":"Chesneau","year":"2014","journal-title":"Bone"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"708","DOI":"10.1097\/MOP.0000000000000813","article-title":"Osteogenesis imperfecta: Advancements in genetics and treatment","volume":"31","author":"Rossi","year":"2019","journal-title":"Curr. Opin. Pediatr."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Nguyen, H.T.T., Vu, D.C., Nguyen, D.M., Dang, Q.D., Tran, V.K., Le, H., and Tong, S.M. (2021). Dentinogenesis Imperfecta and Caries in Osteogenesis Imperfecta among Vietnamese Children. Dent. J., 9.","DOI":"10.3390\/dj9050049"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1111\/scd.12330","article-title":"Oral manifestations of Langerhans cell histiocytosis: A case series","volume":"38","author":"Fernandes","year":"2018","journal-title":"Spec. Care Dent."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"151536","DOI":"10.1016\/j.anndiagpath.2020.151536","article-title":"Oral manifestations of Langerhans cell histiocytosis with unusual histomorphologic features","volume":"47","author":"AbdullGaffar","year":"2020","journal-title":"Ann. Diagn. Pathol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"e7645","DOI":"10.1002\/ccr3.7645","article-title":"Langerhans cell histiocytosis in a pediatric patient: A typical presentation with oral manifestations","volume":"11","author":"Shakya","year":"2023","journal-title":"Clin. Case Rep."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1197","DOI":"10.1016\/j.joms.2008.12.016","article-title":"Arthrogryposis multiplex congenita in association with bilateral temporomandibular joint hypomobility: Report of a case and review of literature","volume":"68","author":"Nordone","year":"2010","journal-title":"J. Oral Maxillofac. Surg."},{"key":"ref_14","first-page":"35","article-title":"Arthrogryposis, ectodermal dysplasia and other anomalies in two sisters","volume":"3","author":"Stoll","year":"1992","journal-title":"Genet. Couns."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"116955","DOI":"10.1016\/j.bone.2023.116955","article-title":"Arthrogryposis multiplex congenita: Dental and maxillofacial phenotype\u2014A scoping review","volume":"179","author":"Taqi","year":"2024","journal-title":"Bone"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1002\/ajmg.1320140219","article-title":"Brief clinical report: New, autosomal dominant form of ectodermal dysplasia","volume":"14","author":"Tuffli","year":"1983","journal-title":"Am. J. Med. Genet."},{"key":"ref_17","first-page":"45","article-title":"Chronology of deciduous and permanent dentition in Japanese children II Part 1: Deciduous dentition","volume":"57","author":"Arita","year":"2019","journal-title":"Jpn. J. Ped. Dent."},{"key":"ref_18","first-page":"205","article-title":"Inherited retarded eruption in the permanent dentition","volume":"21","author":"Rasmussen","year":"1997","journal-title":"J. Clin. Pediatr. Dent."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1016\/j.ajodo.2003.10.031","article-title":"Delayed tooth eruption: Pathogenesis, diagnosis, and treatment. A literature review","volume":"126","author":"Suri","year":"2004","journal-title":"Am. J. Orthod. Dentofac. Orthop."},{"key":"ref_20","unstructured":"(2024, October 05). Standard Values for Body Size of Japanese Children in 2000. Available online: https:\/\/auxology.jp\/ja-children-physique."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1032","DOI":"10.4065\/83.9.1032","article-title":"Bisphosphonates: Mechanism of action and role in clinical practice","volume":"83","author":"Drake","year":"2008","journal-title":"Mayo Clin. Proc."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"115566","DOI":"10.1016\/j.bone.2020.115566","article-title":"Bisphosphonates and lifespan","volume":"141","author":"Center","year":"2020","journal-title":"Bone"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1007\/s00223-002-0025-x","article-title":"Bisphosphonate actions on cancer","volume":"73","author":"Yoneda","year":"2003","journal-title":"Calcif. Tissue Int."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1222","DOI":"10.1016\/j.mehy.2007.04.012","article-title":"Trigger osteoclast formation and activation: Molecular treatment strategy of delayed tooth eruption","volume":"69","author":"Hua","year":"2007","journal-title":"Med. Hypotheses"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"167","DOI":"10.17796\/jcpd.29.2.hq7307703428nt3v","article-title":"Dental abnormalities of a long-term survivor of a childhood hematological malignancy: Literature review and report of a case","volume":"29","author":"Zarina","year":"2005","journal-title":"J. Clin. Pediatr. Dent."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"243","DOI":"10.5005\/jp-journals-10005-1614","article-title":"Long-term Adverse Effects of Acute Myeloid Leukemia Treatment on Odontogenesis in a Child","volume":"12","author":"Hernandez","year":"2019","journal-title":"Int. J. Clin. Pediatr. Dent."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Akitomo, T., Ogawa, M., Kaneki, A., Nishimura, T., Usuda, M., Kametani, M., Kusaka, S., Asao, Y., Iwamoto, Y., and Tachikake, M. (2024). Dental Abnormalities in Pediatric Patients Receiving Chemotherapy. J. Clin. Med., 13.","DOI":"10.3390\/jcm13102877"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1177\/0022034519882692","article-title":"Mesenchymal Progenitor Regulation of Tooth Eruption: A View from PTHrP","volume":"99","author":"Nagata","year":"2020","journal-title":"J. Dent. Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1007\/s00223-020-00666-7","article-title":"New Function of RUNX2 in Regulating Osteoclast Differentiation via the AKT\/NFATc1\/CTSK Axis","volume":"106","author":"Xin","year":"2020","journal-title":"Calcif. Tissue Int."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1034\/j.1600-0714.2000.290907.x","article-title":"Tooth eruption in a patient with craniometaphyseal dysplasia: Case report","volume":"29","author":"Hayashibara","year":"2000","journal-title":"J. Oral Pathol. Med."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Akitomo, T., Asao, Y., Iwamoto, Y., Kusaka, S., Usuda, M., Kametani, M., Ando, T., Sakamoto, S., Mitsuhata, C., and Kajiya, M. (2023). A Third Supernumerary Tooth Occurring in the Same Region: A Case Report. Dent. J., 11.","DOI":"10.3390\/dj11020049"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Akitomo, T., Kusaka, S., Usuda, M., Kametani, M., Kaneki, A., Nishimura, T., Ogawa, M., Mitsuhata, C., and Nomura, R. (2023). Fusion of a Tooth with a Supernumerary Tooth: A Case Report and Literature Review of 35 Cases. Children, 11.","DOI":"10.3390\/children11010006"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1016\/j.jdsr.2022.08.002","article-title":"Primary failure of tooth eruption: Etiology and management","volume":"58","author":"Yamaguchi","year":"2022","journal-title":"Jpn. Dent. Sci. Rev."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/j.jobcr.2023.01.001","article-title":"Primary failure of eruption: From molecular diagnosis to therapeutic management","volume":"13","author":"Wagner","year":"2023","journal-title":"J. Oral Biol. Craniofac. Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1098","DOI":"10.1210\/jc.2011-3082","article-title":"Potential effects of alendronate on fibroblast growth factor 23 levels and effective control of hypercalciuria in an adult with Jansen\u2019s metaphyseal chondrodysplasia","volume":"97","author":"Onuchic","year":"2012","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Akitomo, T., Kusaka, S., Iwamoto, Y., Usuda, M., Kametani, M., Asao, Y., Nakano, M., Tachikake, M., Mitsuhata, C., and Nomura, R. (2023). Five-Year Follow-Up of a Child with Non-Syndromic Oligodontia from before the Primary Dentition Stage: A Case Report. Children, 10.","DOI":"10.3390\/children10040717"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Kametani, M., Akitomo, T., Usuda, M., Kusaka, S., Asao, Y., Nakano, M., Iwamoto, Y., Tachikake, M., Ogawa, M., and Kaneki, A. (2024). Evaluation of Periodontal Status and Oral Health Habits with Continual Dental Support for Young Patients with Hemophilia. Appl. Sci., 14.","DOI":"10.3390\/app14041349"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Akitomo, T., Tsuge, Y., Mitsuhata, C., and Nomura, R. (2024). A Narrative Review of the Association between Dental Abnormalities and Chemotherapy. J. Clin. Med., 13.","DOI":"10.3390\/jcm13164942"}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/17\/11\/1521\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:30:28Z","timestamp":1760113828000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/17\/11\/1521"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,12]]},"references-count":38,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2024,11]]}},"alternative-id":["ph17111521"],"URL":"https:\/\/doi.org\/10.3390\/ph17111521","relation":{},"ISSN":["1424-8247"],"issn-type":[{"type":"electronic","value":"1424-8247"}],"subject":[],"published":{"date-parts":[[2024,11,12]]}}}