{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,2]],"date-time":"2026-01-02T17:06:23Z","timestamp":1767373583888,"version":"3.40.5"},"reference-count":43,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2022,8,7]],"date-time":"2022-08-07T00:00:00Z","timestamp":1659830400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002322","name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior","doi-asserted-by":"publisher","award":["88887.696527\/2022\u201000","99999.007007\/2015\u201009"],"award-info":[{"award-number":["88887.696527\/2022\u201000","99999.007007\/2015\u201009"]}],"id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical &amp; Exp Dental Res"],"published-print":{"date-parts":[[2022,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objectives<\/jats:title><jats:p>The aim of this study is to investigate the long\u2010term effects on jaw and femur bone induced by oncologic doses of zoledronic acid in a young rat model.<\/jats:p><\/jats:sec><jats:sec><jats:title>Material and Methods<\/jats:title><jats:p>Six 12\u2010week\u2010old male Wistar rats received zoledronic acid (0.6\u2009mg\/kg) and six control rats received saline solution in the same volume. Compounds were administered intraperitoneally in five doses every 28 days. Euthanasia was performed 150 days after therapy onset. After animal sacrifice, their mandibles and femurs were scanned ex vivo using a high\u2010resolution (14\u2009\u03bcm) micro\u2010computed tomography. Morphometric bone parameters were calculated using CT\u2010Analyzer (Bruker, Belgium) between the first and second mandibular molars\u00a0and in the distal femur metaphysis and epiphysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The treatment group as compared to the controls showed a significantly (<jats:italic>p<\/jats:italic>\u2009&lt;\u2009.05) increased bone quantity (\u2191BV\/TV, \u2193Po[Tot], \u2191Tb.Th), bone density (\u2191TMD, \u2191BMD), and osteosclerosis of the trabecular bone (\u2193Tb.Sp, \u2193Conn.Dn, \u2193Tb.Pf, \u2193SMI) in all anatomical sites. Bone remodeling suppression due to zoledronic acid treatment was more pronounced (<jats:italic>p<\/jats:italic>\u2009&lt;\u2009.05) in the femoral metaphysis relative to the mandible and epiphysis. The exploratory linear discriminant analysis showed that for the mandible, it was mainly the bone quantity\u2010related morphometric indices (BV\/TV\u00a0and Tb.Th), while for the femoral epiphysis and metaphysis, it was bone structure\u2010related (Tb.Pf and Tb.N), which are of primary importance to study the treatment effect.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>High doses of bisphosphonates can differently affect the bone quantity, density, and structure in long bones and jawbones. In the metaphysis, bone changes were primarily concentrated in the region of the growth plate. Future studies may consider the use of bone morphometric indices to evaluate the effect of bisphosphonates.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cre2.643","type":"journal-article","created":{"date-parts":[[2022,8,7]],"date-time":"2022-08-07T16:17:56Z","timestamp":1659889076000},"page":"1487-1495","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["High doses of zoledronic acid induce differential effects on femur and jawbone microstructure"],"prefix":"10.1002","volume":"8","author":[{"given":"Mariana Q. S.","family":"Soares","sequence":"first","affiliation":[{"name":"Department of Surgery, Stomatology, Pathology and Radiology, Bauru School of Dentistry University of S\u00e3o Paulo  Bauru Brazil"},{"name":"OMFS\u2010IMPATH Research Group, Department of Imaging and Pathology Faculty of Medicine, KU Leuven and Oral and Maxillofacial Surgery, University Hospitals Leuven  Leuven Belgium"},{"name":"Division of Oral Radiology Faculdade S\u00e3o Leopoldo Mandic, Instituto de Pesquisa S\u00e3o Leopoldo Mandic  Campinas Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5084-8710","authenticated-orcid":false,"given":"Jeroen","family":"Van Dessel","sequence":"additional","affiliation":[{"name":"Department of Surgery, Stomatology, Pathology and Radiology, Bauru School of Dentistry University of S\u00e3o Paulo  Bauru Brazil"},{"name":"OMFS\u2010IMPATH Research Group, Department of Imaging and Pathology Faculty of Medicine, KU Leuven and Oral and Maxillofacial Surgery, University Hospitals Leuven  Leuven Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3461-0363","authenticated-orcid":false,"given":"Reinhilde","family":"Jacobs","sequence":"additional","affiliation":[{"name":"OMFS\u2010IMPATH Research Group, Department of Imaging and Pathology Faculty of Medicine, KU Leuven and Oral and Maxillofacial Surgery, University Hospitals Leuven  Leuven Belgium"},{"name":"Department of Dental Medicine Karolinska Institutet  Stockholm Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gustavo Z.","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Department of Surgery, Stomatology, Pathology and Radiology, Bauru School of Dentistry University of S\u00e3o Paulo  Bauru Brazil"},{"name":"Department of Surgery and Stomatology, School of Dentistry University Center of Maring\u00e1  Maring\u00e1 Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0674-3759","authenticated-orcid":false,"given":"Paulo S\u00e9rgio","family":"da Silva Santos","sequence":"additional","affiliation":[{"name":"Department of Surgery, Stomatology, Pathology and Radiology, Bauru School of Dentistry University of S\u00e3o Paulo  Bauru Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2699-8564","authenticated-orcid":false,"given":"Laura F.\u00a0P.","family":"Nicolielo","sequence":"additional","affiliation":[{"name":"OMFS\u2010IMPATH Research Group, Department of Imaging and Pathology Faculty of Medicine, KU Leuven and Oral and Maxillofacial Surgery, University Hospitals Leuven  Leuven Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3051-737X","authenticated-orcid":false,"given":"Marco A. H.","family":"Duarte","sequence":"additional","affiliation":[{"name":"Department of Dentistry,\u00a0Endodontics and Dental Materials, Bauru School of Dentistry University of S\u00e3o Paulo  Bauru Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5069-9433","authenticated-orcid":false,"given":"Izabel R. F.","family":"Rubira\u2010Bullen","sequence":"additional","affiliation":[{"name":"Department of Surgery, Stomatology, Pathology and Radiology, Bauru School of Dentistry University of S\u00e3o Paulo  Bauru Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,8,7]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.453"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.141"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1159\/000447425"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00441-007-0499-y"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.157"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00198-012-1947-4"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1177\/1078155220907965"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11657-018-0457-1"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bonr.2018.03.003"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0091317"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00198-014-2857-4"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijom.2019.08.004"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00223-010-9366-z"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00784-009-0300-6"},{"key":"e_1_2_9_16_1","first-page":"3","article-title":"Long\u2010term effects of zolendronic acid on alveolar bone remodeling and quality in the jaw of an oncological rat model","volume":"1","author":"Imada T. S. N.","year":"2018","journal-title":"Global Dentistry"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.oraloncology.2014.02.013"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0722.2008.00529.x"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1586\/ecp.09.40"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbo.2019.100259"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/hed.21422"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00223-020-00707-1"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2013.08.006"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2019.01.003"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.3000410"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-09-0426"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbiomech.2008.09.028"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00441-017-2574-3"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joms.2013.11.005"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joms.2014.04.031"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2011.04.022"},{"key":"e_1_2_9_32_1","first-page":"624","article-title":"The laboratory rat: Relating its age with human's","volume":"4","author":"Sengupta P.","year":"2013","journal-title":"International Journal of Preventive Medicine"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.253"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1111\/jpc.13768"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joms.2018.03.007"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2017-02025"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1259\/dmfr.20130145"},{"key":"e_1_2_9_38_1","first-page":"95","article-title":"Accuracy and reliability of different cone beam computed tomography (CBCT) devices for structural analysis of alveolar bone in comparison with multislice CT and micro\u2010CT","volume":"10","author":"Van Dessel J.","year":"2017","journal-title":"European Journal of Oral Implantology"},{"key":"e_1_2_9_39_1","first-page":"411","article-title":"Quantification of bone quality using different cone beam computed tomography devices: Accuracy assessment for edentulous human mandibles","volume":"9","author":"Van Dessel J.","year":"2016","journal-title":"European Journal of Oral Implantology"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.2805"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1111\/odi.12587"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2016-3745"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1601-0825.2010.01772.x"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.12659\/MSM.916978"}],"container-title":["Clinical and Experimental Dental Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cre2.643","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cre2.643","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cre2.643","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,20]],"date-time":"2023-08-20T00:02:27Z","timestamp":1692489747000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/cre2.643"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,8,7]]},"references-count":43,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2022,12]]}},"alternative-id":["10.1002\/cre2.643"],"URL":"https:\/\/doi.org\/10.1002\/cre2.643","archive":["Portico"],"relation":{},"ISSN":["2057-4347","2057-4347"],"issn-type":[{"type":"print","value":"2057-4347"},{"type":"electronic","value":"2057-4347"}],"subject":[],"published":{"date-parts":[[2022,8,7]]},"assertion":[{"value":"2021-12-14","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-07-22","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-08-07","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}