{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T16:27:50Z","timestamp":1792686470964,"version":"4.5.0"},"reference-count":42,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2012,1,20]],"date-time":"2012-01-20T00:00:00Z","timestamp":1327017600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100000072","name":"National Institute of Dental and Craniofacial Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000072","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["7R21DE018143-03"],"award-info":[{"award-number":["7R21DE018143-03"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2012,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Learning Objectives<\/jats:title>\n                    <jats:p>After completing this course, the reader will be able to: Explain the association between bisphosphonates and osteonecrosis of the jaw.Describe the role of RBMS3 in the risk of BRONJ development.<\/jats:p>\n                    <jats:p>This article is available for continuing medical education credit at CME.TheOncologist.com<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a serious adverse drug reaction. We conducted a genomewide association study to search for genetic variants with a large effect size that increase the risk for BRONJ.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods.<\/jats:title>\n                    <jats:p>We ascertained BRONJ cases according to the diagnostic criteria of the American Association of Oral and Maxillofacial Surgeons. We genotyped cases and a set of treatment-matched controls using Illumina Human Omni Express 12v1 chip (733,202 markers). To maximize the power of the study, we expanded the initial control set by including population and treatment-tolerant controls from publicly available sources. Imputation at the whole-genome level was performed to increase the number of single nucleotide polymorphisms (SNPs) investigated. Tests of association were carried out by logistic regression, adjusting for population structure. We also examined a list of candidate genes comprising genes potentially involved in the pathogenesis of BRONJ and genes related to drug absorption, distribution, metabolism, and excretion.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results.<\/jats:title>\n                    <jats:p>Based on principal component analysis, we initially analyzed 30 white cases and 17 treatment-tolerant controls. We subsequently expanded the control set to include 60 genetically matched controls per case. Association testing identified a significant marker in the RBMS3 gene, rs17024608 (p-value &amp;lt; 7 \u00d7 10\u22128); individuals positive for the SNP were 5.8\u00d7 more likely to develop BRONJ (odds ratio, 5.8; 95% confidence interval, 3.1\u201311.1). Candidate gene analysis further identified SNPs in IGFBP7 and ABCC4 as potentially implicated in BRONJ risk.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion.<\/jats:title>\n                    <jats:p>Our findings suggest that genetic susceptibility plays a role in the pathophysiology of BRONJ, with RBMS3 having a significant effect in the risk.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1634\/theoncologist.2011-0202","type":"journal-article","created":{"date-parts":[[2012,1,21]],"date-time":"2012-01-21T01:49:37Z","timestamp":1327110577000},"page":"279-287","source":"Crossref","is-referenced-by-count":104,"title":["Genomewide Pharmacogenetics of Bisphosphonate-Induced Osteonecrosis of the Jaw: The Role of\n                    <i>RBMS3<\/i>"],"prefix":"10.1093","volume":"17","author":[{"given":"Paola","family":"Nicoletti","sequence":"first","affiliation":[{"name":"a Center for Computational Biology and Bioinformatics, Columbia University Medical Center, New York, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vassiliki M.","family":"Cartsos","sequence":"additional","affiliation":[{"name":"d Department of Orthodontics, Tufts School of Dental Medicine, Boston, Massachusetts, USA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Penelope K.","family":"Palaska","sequence":"additional","affiliation":[{"name":"d Department of Orthodontics, Tufts School of Dental Medicine, Boston, Massachusetts, USA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yufeng","family":"Shen","sequence":"additional","affiliation":[{"name":"a Center for Computational Biology and Bioinformatics, Columbia University Medical Center, New York, New York, USA"},{"name":"b Department of Biomedical Informatics, Columbia University Medical Center, New York, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aris","family":"Floratos","sequence":"additional","affiliation":[{"name":"a Center for Computational Biology and Bioinformatics, Columbia University Medical Center, New York, New York, USA"},{"name":"b Department of Biomedical Informatics, Columbia University Medical Center, New York, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Athanasios I.","family":"Zavras","sequence":"additional","affiliation":[{"name":"a Center for Computational Biology and Bioinformatics, Columbia University Medical Center, New York, New York, USA"},{"name":"c Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, New York, USA;"},{"name":"e Division of Oral Epidemiology & Biostatistics, Columbia College of Dental Medicine, New York, New York, USA;"},{"name":"f Department of Epidemiology, Mailman School of Public Health, New York, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2012,1,20]]},"reference":[{"key":"2021122308120163300_B1","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1111\/j.1749-6632.2010.05876.x","article-title":"The impact of bisphosphonates on oral health: Lessons from the past and opportunities for the future","volume":"1218","author":"Zavras","year":"2011","journal-title":"Ann N Y Acad Sci"},{"key":"2021122308120163300_B2","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1111\/j.1834-7819.2010.01283.x","article-title":"A review of the clinical implications of bisphosphonates in dentistry","volume":"56","author":"Borromeo","year":"2011","journal-title":"Aust Dent J"},{"key":"2021122308120163300_B3","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/j.bone.2008.09.012","article-title":"Osteonecrosis of the jaw: Who gets it, and why?","volume":"44","author":"Reid","year":"2009","journal-title":"Bone"},{"key":"2021122308120163300_B4","first-page":"6538","article-title":"Bisphosphonates inhibit angiogenesis in vitro and testosterone-stimulated vascular regrowth in the ventral prostate in castrated rats","volume":"62","author":"Fournier","year":"2002","journal-title":"Cancer Res"},{"key":"2021122308120163300_B5","volume-title":"Position Paper on Bisphosphonate-Related Osteonecrosis of the Jaw\u20142009 Update","author":"American Association of Oral and Maxillofacial Surgeons"},{"key":"2021122308120163300_B6","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1111\/j.1749-6632.2010.05771.x","article-title":"Epidemiology and risk factors for osteonecrosis of the jaw in cancer patients","volume":"1218","author":"Hoff","year":"2011","journal-title":"Ann N Y Acad Sci"},{"key":"2021122308120163300_B7","doi-asserted-by":"crossref","first-page":"945","DOI":"10.1200\/JCO.2005.04.2465","article-title":"Osteonecrosis of the jaw in multiple myeloma patients: Clinical features and risk factors","volume":"24","author":"Badros","year":"2006","journal-title":"J Clin Oncol"},{"key":"2021122308120163300_B8","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1016\/j.joms.2007.11.032","article-title":"Zoledronate, smoking, and obesity are strong risk factors for osteonecrosis of the jaw: A case-control study","volume":"66","author":"Wessel","year":"2008","journal-title":"J Oral Maxillofac Surg"},{"key":"2021122308120163300_B9","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1097\/FPC.0b013e328335729c","article-title":"Bisphosphonates pathway","volume":"21","author":"Gong","year":"2011","journal-title":"Pharmacogenet Genomics"},{"key":"2021122308120163300_B10","doi-asserted-by":"crossref","first-page":"2709","DOI":"10.1182\/blood-2008-04-147884","article-title":"Bisphosphonate-related osteonecrosis of the jaw is associated with polymorphisms of the cytochrome P450 CYP2C8 in multiple myeloma: A genome-wide single nucleotide polymorphism analysis","volume":"112","author":"Sarasquete","year":"2008","journal-title":"Blood"},{"key":"2021122308120163300_B11","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1038\/ng1488","article-title":"A single-nucleotide polymorphism tagging set for human drug metabolism and transport","volume":"37","author":"Ahmadi","year":"2005","journal-title":"Nat Genet"},{"key":"2021122308120163300_B12","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1086\/519795","article-title":"PLINK: A tool set for whole-genome association and population-based linkage analyses","volume":"81","author":"Purcell","year":"2007","journal-title":"Am J Hum Genet"},{"key":"2021122308120163300_B13","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1016\/j.ajhg.2008.08.005","article-title":"The population reference sample, POPRES: A resource for population, disease, and pharmacological genetics research","volume":"83","author":"Nelson","year":"2008","journal-title":"Am J Hum Genet"},{"key":"2021122308120163300_B14","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1038\/nature05911","article-title":"Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls","volume":"447","author":"Wellcome Trust Case Control Consortium","year":"2007","journal-title":"Nature"},{"key":"2021122308120163300_B15","volume-title":"Science\/Illumina iControlDB","author":"illumina\u00ae"},{"key":"2021122308120163300_B16","article-title":"Genome-wide association study of serious blistering skin rash caused by drugs","author":"Shen","year":"2011","journal-title":"Pharmacogenomics J"},{"key":"2021122308120163300_B17","doi-asserted-by":"crossref","first-page":"904","DOI":"10.1038\/ng1847","article-title":"Principal components analysis corrects for stratification in genome-wide association studies","volume":"38","author":"Price","year":"2006","journal-title":"Nat Genet"},{"key":"2021122308120163300_B18","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1038\/nature07331","article-title":"Genes mirror geography within Europe","volume":"456","author":"Novembre","year":"2008","journal-title":"Nature"},{"key":"2021122308120163300_B19","doi-asserted-by":"crossref","first-page":"4674","DOI":"10.1200\/JCO.2010.28.5064","article-title":"Genome-wide associations and functional genomic studies of musculoskeletal adverse events in women receiving aromatase inhibitors","volume":"28","author":"Ingle","year":"2010","journal-title":"J Clin Oncol"},{"key":"2021122308120163300_B20","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1038\/nrg2796","article-title":"Genotype imputation for genome-wide association studies","volume":"11","author":"Marchini","year":"2010","journal-title":"Nat Rev Genet"},{"key":"2021122308120163300_B21","doi-asserted-by":"crossref","first-page":"e1000529","DOI":"10.1371\/journal.pgen.1000529","article-title":"A flexible and accurate genotype imputation method for the next generation of genome-wide association studies","volume":"5","author":"Howie","year":"2009","journal-title":"PLoS Genet"},{"key":"2021122308120163300_B22","doi-asserted-by":"crossref","first-page":"1665","DOI":"10.1101\/gr.6861907","article-title":"PennCNV: An integrated hidden Markov model designed for high-resolution copy number variation detection in whole-genome SNP genotyping data","volume":"17","author":"Wang","year":"2007","journal-title":"Genome Res"},{"key":"2021122308120163300_B23","doi-asserted-by":"crossref","first-page":"e1000373","DOI":"10.1371\/journal.pgen.1000373","article-title":"A genome-wide investigation of SNPs and CNVs in schizophrenia","volume":"5","author":"Need","year":"2009","journal-title":"PLoS Genet"},{"key":"2021122308120163300_B24","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1186\/1471-2105-8-426","article-title":"DAVID Knowledgebase: A gene-centered database integrating heterogeneous gene annotation resources to facilitate high-throughput gene functional analysis","volume":"8","author":"Sherman","year":"2007","journal-title":"BMC Bioinformatics"},{"issue":"suppl 1","key":"2021122308120163300_B25","doi-asserted-by":"crossref","first-page":"D355","DOI":"10.1093\/nar\/gkp896","article-title":"KEGG for representation and analysis of molecular networks involving diseases and drugs","volume":"38","author":"Kanehisa","year":"2010","journal-title":"Nucleic Acids Res"},{"key":"2021122308120163300_B26","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1038\/nature09298","article-title":"International HapMap 3 Consortium. Integrating common and rare genetic variation in diverse human populations","volume":"467","author":"Altshuler","year":"2010","journal-title":"Nature"},{"key":"2021122308120163300_B27","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1634\/theoncologist.2010-0183","article-title":"Quality of life implications of bisphosphonate-associated osteonecrosis of the jaw","volume":"16","author":"Miksad","year":"2011","journal-title":"The Oncologist"},{"key":"2021122308120163300_B28","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1016\/j.jmb.2007.06.006","article-title":"RNA-binding protein RBMS3 is expressed in activated hepatic stellate cells and liver fibrosis and increases expression of transcription factor Prx1","volume":"371","author":"Fritz","year":"2007","journal-title":"J Mol Biol"},{"key":"2021122308120163300_B29","doi-asserted-by":"crossref","first-page":"1377","DOI":"10.1016\/S0140-6736(04)16051-0","article-title":"Osteogenesis imperfecta","volume":"363","author":"Rauch","year":"2004","journal-title":"Lancet"},{"issue":"suppl 1","key":"2021122308120163300_B30","doi-asserted-by":"crossref","first-page":"S14","DOI":"10.1186\/1471-2350-8-S1-S14","article-title":"Genome-wide association with bone mass and geometry in the Framingham Heart Study","volume":"8","author":"Kiel","year":"2007","journal-title":"BMC Med Genet"},{"key":"2021122308120163300_B31","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1007\/s00223-001-1035-9","article-title":"COLIA1 Sp1 polymorphism predicts response of femoral neck bone density to cyclical etidronate therapy","volume":"70","author":"Qureshi","year":"2002","journal-title":"Calcif Tissue Int"},{"key":"2021122308120163300_B32","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1016\/j.bone.2008.01.003","article-title":"Osteonecrosis of the jaw and bisphosphonate treatment for osteoporosis","volume":"42","author":"Rizzoli","year":"2008","journal-title":"Bone"},{"key":"2021122308120163300_B33","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1007\/s00784-009-0312-2","article-title":"Expression profile and synthesis of different collagen types I, II, III, and V of human gingival fibroblasts, osteoblasts, and SaOS-2 cells after bisphosphonate treatment","volume":"14","author":"Simon","year":"2010","journal-title":"Clin Oral Investig"},{"key":"2021122308120163300_B34","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1038\/428486a","article-title":"Medical genetics: A marker for Stevens-Johnson syndrome","volume":"428","author":"Chung","year":"2004","journal-title":"Nature"},{"key":"2021122308120163300_B35","doi-asserted-by":"crossref","first-page":"816","DOI":"10.1038\/ng.379","article-title":"HLA-B*5701 genotype is a major determinant of drug-induced liver injury due to flucloxacillin","volume":"41","author":"Daly","year":"2009","journal-title":"Nat Genet"},{"key":"2021122308120163300_B36","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1097\/FPC.0b013e3282f3ef9c","article-title":"A European study of HLA-B in Stevens-Johnson syndrome and toxic epidermal necrolysis related to five high-risk drugs","volume":"18","author":"Lonjou","year":"2008","journal-title":"Pharmacogenet Genomics"},{"key":"2021122308120163300_B37","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1124\/jpet.108.136523","article-title":"The human multidrug resistance protein 4 (MRP4, ABCC4): Functional analysis of a highly polymorphic gene","volume":"325","author":"Abla","year":"2008","journal-title":"J Pharmacol Exp Ther"},{"key":"2021122308120163300_B38","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1038\/jhg.2009.79","article-title":"Association study of genetic polymorphism in ABCC4 with cyclophosphamide-induced adverse drug reactions in breast cancer patients","volume":"54","author":"Low","year":"2009","journal-title":"J Hum Genet"},{"key":"2021122308120163300_B39","volume-title":"Mecasermin (Increlex, Tercica) prescribing and safety information","author":"U.S. Food and Drug Administration"},{"key":"2021122308120163300_B40","first-page":"49","article-title":"The effects of growth hormone on cortical and cancellous bone","volume":"2","author":"Andreassen","year":"2001","journal-title":"J Musculoskelet Neuronal Interact"},{"key":"2021122308120163300_B41","doi-asserted-by":"crossref","first-page":"275","DOI":"10.2174\/1381612013398167","article-title":"Pharmacological interference with transcriptional control of osteoblasts: A possible role for leptin and fatty acids in maintaining bone strength and body lean mass","volume":"7","author":"Gordeladze","year":"2001","journal-title":"Curr Pharm Des"},{"key":"2021122308120163300_B42","first-page":"266","volume-title":"Osteoporosis","author":"Canalis","year":"1996"}],"container-title":["The Oncologist"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1634\/theoncologist.2011-0202","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1634\/theoncologist.2011-0202","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/oncolo\/article-pdf\/17\/2\/279\/41860371\/oncolo_17_2_279.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/oncolo\/article-pdf\/17\/2\/279\/41860371\/oncolo_17_2_279.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,12,23]],"date-time":"2021-12-23T14:36:37Z","timestamp":1640270197000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/oncolo\/article\/17\/2\/279\/6403343"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,1,20]]},"references-count":42,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2012,1,20]]},"published-print":{"date-parts":[[2012,2,1]]}},"URL":"https:\/\/doi.org\/10.1634\/theoncologist.2011-0202","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.13664958.15067080","asserted-by":"object"}]},"ISSN":["1083-7159","1549-490X"],"issn-type":[{"value":"1083-7159","type":"print"},{"value":"1549-490X","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2012,2,1]]},"published":{"date-parts":[[2012,1,20]]}}}