{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T23:30:13Z","timestamp":1790119813380,"version":"4.0.1"},"reference-count":43,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2023,1,25]],"date-time":"2023-01-25T00:00:00Z","timestamp":1674604800000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2023,1,25]],"date-time":"2023-01-25T00:00:00Z","timestamp":1674604800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000005","name":"U.S. Department of Defense","doi-asserted-by":"publisher","award":["W81XWH\u201018\u20101\u20100029"],"award-info":[{"award-number":["W81XWH\u201018\u20101\u20100029"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000005","name":"U.S. Department of Defense","doi-asserted-by":"publisher","award":["W81XWH\u201022\u20101\u20100090"],"award-info":[{"award-number":["W81XWH\u201022\u20101\u20100090"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["asbmr.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["JBMR Plus"],"published-print":{"date-parts":[[2023,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Breast cancer has a high predilection for spreading to bone with approximately 70% of patients who succumb to disease harboring bone disseminated tumor cells. Despite this high prevalence, treatments for bone metastatic breast cancer predominantly manage morbidities, including pain and hypercalcemia, rather than reducing bone metastasis incidence or growth. Histone deacetylase inhibitors (HDACi), including panobinostat, entinostat, and valproic acid, typically slow primary tumor progression and are currently in clinical trials for the treatment of many cancers, including primary and metastatic breast cancer, but their effects on bone metastatic disease have not been examined in preclinical models. We report that treatment with the HDACi panobinostat, but not entinostat or valproic acid, significantly reduced trabecular bone volume in tumor\u2010na\u00efve mice, consistent with previous reports of HDACi\u2010induced bone loss. Surprisingly, treatment with entinostat or panobinostat, but not valproic acid, increased tumor burden and incidence in an experimental model of breast cancer bone metastasis. In vitro, multiple HDACi stimulated expression of pro\u2010osteolytic genes in breast tumor cells, suggesting this may be a mechanism by which HDACi fuel tumor growth. In support of this, combination therapy of panobinostat or entinostat with the antiresorptive bisphosphonate zoledronic acid prevented bone metastatic progression; however, the addition of zoledronic acid to panobinostat therapy failed to fully correct panobinostat\u2010induced bone loss. Together these data demonstrate that select HDACi fuel bone metastatic growth and provide potential mechanistic and therapeutic avenues to offset these effects. \u00a9 2022 The Authors.\n                    <jats:italic>JBMR Plus<\/jats:italic>\n                    published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.\n                  <\/jats:p>","DOI":"10.1002\/jbm4.10694","type":"journal-article","created":{"date-parts":[[2022,10,21]],"date-time":"2022-10-21T10:55:01Z","timestamp":1666349701000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Select\n                    <scp>HDAC<\/scp>\n                    Inhibitors Enhance Osteolysis and Bone Metastasis Outgrowth but Can Be Mitigated With Bisphosphonate Therapy"],"prefix":"10.1093","volume":"7","author":[{"given":"Miranda E","family":"Clements","sequence":"first","affiliation":[{"name":"Program in Cancer Biology Vanderbilt University  Nashville TN USA"},{"name":"Vanderbilt Center for Bone Biology, Department of Medicine, Division of Clinical Pharmacology Vanderbilt University Medical Center  Nashville TN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren","family":"Holtslander","sequence":"additional","affiliation":[{"name":"Vanderbilt Center for Bone Biology, Department of Medicine, Division of Clinical Pharmacology Vanderbilt University Medical Center  Nashville TN USA"},{"name":"Department of Medicine, Division of Clinical Pharmacology Vanderbilt University Medical Center  Nashville TN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua R","family":"Johnson","sequence":"additional","affiliation":[{"name":"Vanderbilt Center for Bone Biology, Department of Medicine, Division of Clinical Pharmacology Vanderbilt University Medical Center  Nashville TN USA"},{"name":"Department of Medicine, Division of Clinical Pharmacology Vanderbilt University Medical Center  Nashville TN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2755-9851","authenticated-orcid":false,"given":"Rachelle W","family":"Johnson","sequence":"additional","affiliation":[{"name":"Program in Cancer Biology Vanderbilt University  Nashville TN USA"},{"name":"Vanderbilt Center for Bone Biology, Department of Medicine, Division of Clinical Pharmacology Vanderbilt University Medical Center  Nashville TN USA"},{"name":"Department of Medicine, Division of Clinical Pharmacology Vanderbilt University Medical Center  Nashville TN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,1,25]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc3055"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.2147\/CMAR.S176763"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13058-019-1201-5"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2018.00092"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00223-017-0369-x"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nurt.2006.11.007"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1528-1157.2001.416800.x"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.58.9.1348"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2003.11.011"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1167.2008.01640.x"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneurol.2010.341"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjopharm.2010.02.003"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-10-0572"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2011.01.007"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a031252"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00666208"},{"key":"e_1_2_9_18_1","article-title":"Models of bone metastasis","volume":"67","author":"Campbell JP","year":"2012","journal-title":"J Vis Exp"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.3109\/08977194.2014.894037"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-10-2993"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb3408"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-32653-2"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1373\/49.8.1398"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41388-021-01931-1"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2021.644303"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/bonekey.2015.122"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbo.2016.02.008"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11864-018-0535-z"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.33035"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13073-018-0597-3"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-14-0778"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells8010008"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.apsb.2019.08.008"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a026831"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(19)30164-0"},{"key":"e_1_2_9_36_1","unstructured":"Syndax Pharmaceuticals I. ECOG\u2010ACRIN provides Syndax Pharmaceuticals with results of phase 3 E2112 trial of entinostat plus exemestane in patients with HR+ HER2\u2010 breast cancer.2020."},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-16-1729"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2006-2023H"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0185566"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2006.03.011"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12885-019-5379-9"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-14-0621"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2007.12.003"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature20785"}],"container-title":["JBMR Plus"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jbm4.10694","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jbm4.10694","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/asbmr.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jbm4.10694","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jbm4.10694","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,3,14]],"date-time":"2024-03-14T09:57:41Z","timestamp":1710410261000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jbmrplus\/article\/7479101"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,25]]},"references-count":43,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2023,3]]}},"alternative-id":["10.1002\/jbm4.10694"],"URL":"https:\/\/doi.org\/10.1002\/jbm4.10694","archive":["Portico"],"relation":{"has-review":[{"id-type":"doi","id":"10.1002\/JBM4.10694\/v2\/review2","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/JBM4.10694\/v2\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/JBM4.10694\/v1\/review2","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/JBM4.10694\/v1\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/JBM4.10694\/v2\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/JBM4.10694\/v1\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/JBM4.10694\/v2\/response1","asserted-by":"object"}]},"ISSN":["2473-4039","2473-4039"],"issn-type":[{"value":"2473-4039","type":"print"},{"value":"2473-4039","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,1,25]]},"assertion":[{"value":"2022-07-12","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-10-18","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-01-25","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e10694"}}