{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T22:49:51Z","timestamp":1785797391463,"version":"3.56.0"},"reference-count":25,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2015,8,19]],"date-time":"2015-08-19T00:00:00Z","timestamp":1439942400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2016,2,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:sec>\n                  <jats:title>\u2003<\/jats:title>\n                  <jats:p>Osteonecrosis of the jaw (ONJ) is a serious adverse drug event that was initially reported with intravenous bisphosphonates (BPs) and more recently with other classes of drugs such as receptor activator of NF-\u03baB ligand (RANKL) inhibitor, antiangiogenic agents, and mammalian target of rapamycin (m-TOR) inhibitors. The purpose of this study is to analyze the ONJ cases and the associated drugs in the US Food and Drug Administration's adverse event reporting system (FAERS). The FAERS database was queried for the adverse drug events reported from the first quarter of 2010 to the first quarter of 2014. The reporting odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for each queried drug. A total of 17,119 unique ONJ cases were identified. In the overall analysis, the drugs with the highest reporting ORs were BPs: pamidronate (OR\u2009=\u2009498.9), zoledronate (OR\u2009=\u2009171.7), and alendronate (OR\u2009=\u200963.6), whereas denosumab had lower ORs than all the BPs except for etidronate. The antiangiogenic and m-TOR inhibitors had the lowest ORs. In cancer patients who were treated for prevention of skeletal-related events (SREs), the reporting ORs for zoledronate and denosumab were 125.2 and 4.9, respectively. In patients with osteoporosis, the ORs were 1.1 (1.0\u20131.18) for zoledronate and 0.63 (0.56\u20130.70) for denosumab, respectively. Our analysis of the FAERS database showed that the intravenous BPs were associated with the highest risk for ONJ, RANKL inhibitor was associated with risk comparable to BPs used for osteoporosis such as etidronate, and the antiangiogenic agents and m-TOR inhibitors were associated with the lowest risk for ONJ. The high risk for ONJ with zoledronate and denosumab was mainly observed in those who were treated for prevention of SREs, whereas there was limited evidence for such risk in those who were treated for osteoporosis. \u00a9 2015 American Society for Bone and Mineral Research.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1002\/jbmr.2693","type":"journal-article","created":{"date-parts":[[2015,8,19]],"date-time":"2015-08-19T23:45:10Z","timestamp":1440027910000},"page":"336-340","source":"Crossref","is-referenced-by-count":89,"title":["Osteonecrosis of the Jaw in the United States Food and Drug Administration's Adverse Event Reporting System (FAERS)"],"prefix":"10.1093","volume":"31","author":[{"given":"Xiaoyan","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Pharmaceutics and Center for Pharmacometrics and System Pharmacology, College of PharmacyUniversity of FloridaOrlandoFLUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Issam S","family":"Hamadeh","sequence":"additional","affiliation":[{"name":"Center for Pharmacogenomics, College of PharmacyUniversity of FloridaGainesvilleFLUSA"},{"name":"Department of Pharmacotherapy and Translational Research, College of PharmacyUniversity of FloridaGainesvilleFLUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuang","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Pharmacotherapy and Translational Research, College of PharmacyUniversity of FloridaGainesvilleFLUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Katz","sequence":"additional","affiliation":[{"name":"Department of Oral Medicine, College of DentistryUniversity of FloridaGainesvilleFLUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan S","family":"Moreb","sequence":"additional","affiliation":[{"name":"Department of Medicine, College of MedicineUniversity of FloridaGainesvilleFLUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taimour Y","family":"Langaee","sequence":"additional","affiliation":[{"name":"Center for Pharmacogenomics, College of PharmacyUniversity of FloridaGainesvilleFLUSA"},{"name":"Department of Pharmacotherapy and Translational Research, College of PharmacyUniversity of FloridaGainesvilleFLUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lawrence J","family":"Lesko","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics and Center for Pharmacometrics and System Pharmacology, College of PharmacyUniversity of FloridaOrlandoFLUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Gong","sequence":"additional","affiliation":[{"name":"Center for Pharmacogenomics, College of PharmacyUniversity of FloridaGainesvilleFLUSA"},{"name":"Department of Pharmacotherapy and Translational Research, College of PharmacyUniversity of FloridaGainesvilleFLUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2015,8,19]]},"reference":[{"key":"2024021014190341700_jbmr2693-bib-0001","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 Oral Maxillofac Surg."},{"key":"2024021014190341700_jbmr2693-bib-0002","first-page":"369","year":"2007"},{"key":"2024021014190341700_jbmr2693-bib-0003","doi-asserted-by":"crossref","first-page":"826","DOI":"10.1359\/jbmr.080205","article-title":"Frequency and risk factors associated with osteonecrosis of the jaw in cancer patients treated with intravenous bisphosphonates","volume":"23","author":"Hoff","year":"2008","journal-title":"J Bone Miner 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New oncology drugs and osteonecrosis of the jaw (ONJ)","volume":"89","author":"Migliorati","year":"2009","journal-title":"J Tenn Dent Assoc."},{"key":"2024021014190341700_jbmr2693-bib-0010","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1016\/j.bjoms.2009.08.030","article-title":"Osteonecrosis of the jaws induced by anti-RANK ligand therapy","volume":"48","author":"Taylor","year":"2010","journal-title":"Br J Oral Maxillofac Surg."},{"key":"2024021014190341700_jbmr2693-bib-0011","doi-asserted-by":"crossref","first-page":"e302","DOI":"10.1016\/j.bjoms.2013.09.008","article-title":"Osteonecrosis of the jaw related to everolimus: a case report","volume":"51","author":"Kim","year":"2013","journal-title":"Br J Oral Maxillofac Surg."},{"key":"2024021014190341700_jbmr2693-bib-0012","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1016\/j.ctrv.2015.04.007","article-title":"Drug induced osteonecrosis of the jaw","volume":"41","author":"Hamadeh","year":"2015","journal-title":"Cancer Treat Rev."},{"key":"2024021014190341700_jbmr2693-bib-0013","doi-asserted-by":"crossref","first-page":"1938","DOI":"10.1016\/j.joms.2014.04.031","article-title":"American Association of Oral and Maxillofacial Surgeons position paper on medication-related osteonecrosis of the jaw\u20142014 update","volume":"72","author":"Ruggiero","year":"2014","journal-title":"J Oral Maxillofac Surg."},{"key":"2024021014190341700_jbmr2693-bib-0014","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1002\/pds.1742","article-title":"Quantitative signal detection using spontaneous adr reporting","volume":"18","author":"Bate","year":"2009","journal-title":"Pharmacoepidemiol Drug Saf."},{"key":"2024021014190341700_jbmr2693-bib-0015","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1002\/pds.668","article-title":"A comparison of measures of disproportionality for signal detection in spontaneous reporting systems for adverse drug reactions","volume":"11","author":"van Puijenbroek","year":"2002","journal-title":"Pharmacoepidemiol Drug Saf."},{"key":"2024021014190341700_jbmr2693-bib-0016","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1016\/j.joms.2009.03.050","article-title":"Prevalence of osteonecrosis of the jaw in patients with oral bisphosphonate exposure","volume":"68","author":"Lo","year":"2010","journal-title":"J Oral Maxillofac Surg."},{"key":"2024021014190341700_jbmr2693-bib-0017","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1007\/s00774-011-0299-z","article-title":"An epidemiological study of alendronate-related osteonecrosis of the jaws. A case series from the south-east of Scotland with attention given to case definition and prevalence","volume":"30","author":"Malden","year":"2012","journal-title":"J Bone Miner Metab."},{"key":"2024021014190341700_jbmr2693-bib-0018","doi-asserted-by":"crossref","first-page":"1365","DOI":"10.14219\/jada.archive.2010.0082","article-title":"The incidence of osteonecrosis of the jaw in patients receiving 5 milligrams of zoledronic acid: data from the health outcomes and reduced incidence with zoledronic acid once yearly clinical trials program","volume":"141","author":"Grbic","year":"2010","journal-title":"J Am Dent Assoc"},{"key":"2024021014190341700_jbmr2693-bib-0019","doi-asserted-by":"crossref","first-page":"5132","DOI":"10.1200\/JCO.2010.29.7101","article-title":"Denosumab compared with zoledronic acid for the treatment of bone metastases in patients with advanced breast cancer: a randomized, double-blind study","volume":"28","author":"Stopeck","year":"2010","journal-title":"J Clin Oncol."},{"key":"2024021014190341700_jbmr2693-bib-0020","doi-asserted-by":"crossref","first-page":"1125","DOI":"10.1200\/JCO.2010.31.3304","article-title":"Randomized, double-blind study of denosumab versus zoledronic acid in the treatment of bone metastases in patients with advanced cancer (excluding breast and prostate cancer) or multiple myeloma","volume":"29","author":"Henry","year":"2011","journal-title":"J Clin Oncol"},{"key":"2024021014190341700_jbmr2693-bib-0021","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1007\/s00223-004-0024-1","article-title":"From molds and macrophages to mevalonate: a decade of progress in understanding the molecular mode of action of bisphosphonates","volume":"75","author":"Rogers","year":"2004","journal-title":"Calcif Tissue Int."},{"key":"2024021014190341700_jbmr2693-bib-0022","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1007\/s11926-003-0085-6","article-title":"Bisphosphonate mechanism of action","volume":"5","author":"Reszka","year":"2003","journal-title":"Curr Rheumatol Rep."},{"key":"2024021014190341700_jbmr2693-bib-0023","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.1124\/jpet.102.035295","article-title":"Novel antiangiogenic effects of the bisphosphonate compound zoledronic acid","volume":"302","author":"Wood","year":"2002","journal-title":"J Pharmacol Exp Ther."},{"key":"2024021014190341700_jbmr2693-bib-0024","first-page":"672027","article-title":"Decreasing frequency of osteonecrosis of the jaw in cancer and myeloma patients treated with bisphosphonates: the experience of the oncology network of Piedmont and Aosta Valley (north-western italy)","volume":"2013","author":"Fusco","year":"2013","journal-title":"ISRN Oncol."},{"key":"2024021014190341700_jbmr2693-bib-0025","author":"Center","year":"2008"}],"container-title":["Journal of Bone and Mineral Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fjbmr.2693","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fjbmr.2693","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/jbmr\/article-pdf\/31\/2\/336\/56650933\/jbmr2693.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jbmr\/article-pdf\/31\/2\/336\/56650933\/jbmr2693.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,3,13]],"date-time":"2024-03-13T14:55:08Z","timestamp":1710341708000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jbmr\/article\/31\/2\/336-340\/7605392"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,8,19]]},"references-count":25,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2015,8,19]]},"published-print":{"date-parts":[[2016,2,1]]}},"URL":"https:\/\/doi.org\/10.1002\/jbmr.2693","relation":{},"ISSN":["0884-0431","1523-4681"],"issn-type":[{"value":"0884-0431","type":"print"},{"value":"1523-4681","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2016,2,1]]},"published":{"date-parts":[[2015,8,19]]}}}