{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T13:04:15Z","timestamp":1768568655631,"version":"3.49.0"},"reference-count":17,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2012,5,31]],"date-time":"2012-05-31T00:00:00Z","timestamp":1338422400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Oral Pathology Medicine"],"published-print":{"date-parts":[[2012,11]]},"abstract":"<jats:p><jats:italic>J Oral Pathol Med<\/jats:italic> (2012) <jats:bold>41<\/jats:bold>: 788\u2013792<\/jats:p><jats:p><jats:bold>Background:\u2002<\/jats:bold> Osteonecrosis of the jaw (ONJ) is a chronic complication of bisphosphonate therapy, mainly when intravenous, in cancer patients with bone metastases and myeloma. Its pathophysiology is not yet fully elucidated; in particular, the molecular\/cellular events triggering ONJ remain unclear. This complication could result from the effect of bisphosphonates released from bone into the soft\u2010tissues, or from osteolysis induced by soft\u2010tissues directly exposed to bisphosphonates. This research investigated the possibility that ONJ may be evocated by changes induced in osteoblast activity by factors released by soft\u2010tissue cells exposed to zoledronic acid.<\/jats:p><jats:p><jats:bold>Methods:\u2002<\/jats:bold> An \u2018<jats:italic>in vitro<\/jats:italic>\u2019 model was used, in which human osteoblast\u2010like MG\u201063 cells were grown in medium conditioned by human keratinocytes NCTC 2544, exposed or not to zoledronic acid (5 or 50\u2003\u03bcM); 5\u2003\u03bcM zoledronic acid was also directly administered to MG\u201063 cells.<\/jats:p><jats:p><jats:bold>Results:\u2002<\/jats:bold> In NCTC 2544 cells, zoledronic acid decreased proliferation via decreased hydroxy\u20103\u2010methyl\u2010glutaryl\u2010CoA reductase, suggesting that a decrease in healing capability can occur in case of injury. An increased pro\u2010inflammatory potential was also observed. Osteoblasts grown in medium conditioned in the presence of zoledronic acid showed decreased proliferation and osteogenic properties, and increased ability to induce osteoclast differentiation and inflammatory process. Zoledronic acid directly administered to MG\u201063 modulated only some parameters and in a lesser extent.<\/jats:p><jats:p><jats:bold>Conclusions:\u2002<\/jats:bold> The research evidenced, for the first time, the direct involvement of epithelial cells in zoledronic acid\u2010triggered molecular mechanisms leading to osteonecrosis of the jaw, by modulating both osteoblast and osteoclast properties.<\/jats:p>","DOI":"10.1111\/j.1600-0714.2012.01173.x","type":"journal-article","created":{"date-parts":[[2012,5,31]],"date-time":"2012-05-31T11:59:32Z","timestamp":1338465572000},"page":"788-792","source":"Crossref","is-referenced-by-count":24,"title":["Exposing human epithelial cells to zoledronic acid can mediate osteonecrosis of jaw: an <i>in vitro<\/i> model"],"prefix":"10.1111","volume":"41","author":[{"given":"S.","family":"Saracino","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R. A.","family":"Canuto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.","family":"Maggiora","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.","family":"Oraldi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.","family":"Scoletta","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L.","family":"Ciuffreda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A. M.","family":"Vandone","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S.","family":"Carossa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.","family":"Mozzati","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G.","family":"Muzio","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2012,5,31]]},"reference":[{"key":"e_1_2_7_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0278-2391(03)00720-1"},{"key":"e_1_2_7_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0278-2391(03)00328-8"},{"key":"e_1_2_7_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.joms.2004.02.004"},{"key":"e_1_2_7_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjmed.2008.01.047"},{"key":"e_1_2_7_6_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1754-4505.2009.00128.x"},{"key":"e_1_2_7_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejon.2009.12.003"},{"key":"e_1_2_7_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjmed.2008.12.005"},{"key":"e_1_2_7_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.joms.2008.01.038"},{"key":"e_1_2_7_10_2","doi-asserted-by":"publisher","DOI":"10.1186\/1755-1536-3-6"},{"key":"e_1_2_7_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/0076-6879(55)01072-0"},{"key":"e_1_2_7_12_2","doi-asserted-by":"publisher","DOI":"10.1006\/excr.1995.1104"},{"key":"e_1_2_7_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2007.04.196"},{"key":"e_1_2_7_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.joms.2008.01.026"},{"key":"e_1_2_7_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2008.09.012"},{"key":"e_1_2_7_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.abb.2010.09.028"},{"key":"e_1_2_7_17_2","doi-asserted-by":"publisher","DOI":"10.1621\/nrs.08002"},{"key":"e_1_2_7_18_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-2001-15109"}],"container-title":["Journal of Oral Pathology &amp; Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fj.1600-0714.2012.01173.x","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/j.1600-0714.2012.01173.x","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,30]],"date-time":"2023-10-30T09:30:49Z","timestamp":1698658249000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/j.1600-0714.2012.01173.x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,5,31]]},"references-count":17,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2012,11]]}},"alternative-id":["10.1111\/j.1600-0714.2012.01173.x"],"URL":"https:\/\/doi.org\/10.1111\/j.1600-0714.2012.01173.x","archive":["Portico"],"relation":{},"ISSN":["0904-2512","1600-0714"],"issn-type":[{"value":"0904-2512","type":"print"},{"value":"1600-0714","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,5,31]]}}}