{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T15:45:14Z","timestamp":1787499914084,"version":"build-2736575974"},"reference-count":71,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2015,2,28]],"date-time":"2015-02-28T00:00:00Z","timestamp":1425081600000},"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":[[2015,9,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>\u2003<\/jats:title>\n                    <jats:p>Osteonecrosis of the jaws (ONJ) is a significant complication of antiresorptive medications, such as bisphosphonates and denosumab. Antiresorptive discontinuation to promote healing of ONJ lesions remains highly controversial and understudied. Here, we investigated whether antiresorptive discontinuation alters ONJ features in mice, employing the potent bisphosphonate zoledronic acid (ZA) or the receptor activator of NF-\u03baB ligand (RANKL) inhibitor OPG-Fc, utilizing previously published ONJ animal models. Mice were treated with vehicle (veh), ZA, or OPG-Fc for 11 weeks to induce ONJ, and antiresorptives were discontinued for 6 or 10 weeks. Maxillae and mandibles were examined by \u03bcCT imaging and histologically. ONJ features in ZA and OPG-Fc groups included periosteal bone deposition, empty osteocyte lacunae, osteonecrotic areas, and bone exposure, each of which substantially resolved 10 weeks after discontinuing OPG-Fc but not ZA. Full recovery of tartrate-resistant acid phosphatase-positive (TRAP+) osteoclast numbers occurred after discontinuing OPG-Fc but not ZA. Our data provide the first experimental evidence demonstrating that discontinuation of a RANKL inhibitor, but not a bisphosphonate, reverses features of osteonecrosis in mice. It remains unclear whether antiresorptive discontinuation increases the risk of skeletal-related events in patients with bone metastases or fracture risk in osteoporosis patients, but these preclinical data may nonetheless help to inform discussions on the rationale for a \u201cdrug holiday\u201d in managing the ONJ patient. \u00a9 2015 American Society for Bone and Mineral Research.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jbmr.2490","type":"journal-article","created":{"date-parts":[[2015,2,28]],"date-time":"2015-02-28T16:57:44Z","timestamp":1425142664000},"page":"1627-1640","source":"Crossref","is-referenced-by-count":65,"title":["OPG-Fc but Not Zoledronic Acid Discontinuation Reverses Osteonecrosis of the Jaws (ONJ) in Mice"],"prefix":"10.1093","volume":"30","author":[{"given":"Rafael Scaf","family":"de Molon","sequence":"first","affiliation":[{"name":"Department of Diagnosis and SurgerySchool of Dentistry at AraraquaraS\u00e3o Paulo State UniversityAraraquaraBrazil"},{"name":"Division of Diagnostic and Surgical SciencesUCLA School of DentistryLos AngelesCAUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroaki","family":"Shimamoto","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial RadiologyOsaka University Graduate School of DentistryOsakaJapan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga","family":"Bezouglaia","sequence":"additional","affiliation":[{"name":"Division of Diagnostic and Surgical SciencesUCLA School of DentistryLos AngelesCAUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Flavia Q","family":"Pirih","sequence":"additional","affiliation":[{"name":"Division of Associated SpecialtiesUCLA School of DentistryLos AngelesCAUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah M","family":"Dry","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory MedicineDavid Geffen School of Medicine at UCLALos AngelesCAUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Kostenuik","sequence":"additional","affiliation":[{"name":"Department of Periodontics and Oral MedicineSchool of DentistryUniversity of MichiganAnn ArborMIUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rogely W","family":"Boyce","sequence":"additional","affiliation":[{"name":"Department of Comparative Biology and Safety SciencesAmgen Inc.Thousand OaksCAUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denise","family":"Dwyer","sequence":"additional","affiliation":[{"name":"Department of Comparative Biology and Safety SciencesAmgen Inc.Thousand OaksCAUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tara L","family":"Aghaloo","sequence":"additional","affiliation":[{"name":"Division of Diagnostic and Surgical SciencesUCLA School of DentistryLos AngelesCAUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sotirios","family":"Tetradis","sequence":"additional","affiliation":[{"name":"Molecular Biology InstituteUCLALos AngelesCAUSA"},{"name":"Division of Diagnostic and Surgical SciencesUCLA School of DentistryLos AngelesCAUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2015,2,28]]},"reference":[{"key":"2024020319041626500_jbmr2490-bib-0001","first-page":"23","article-title":"The key role of bisphosphonates in the supportive care of cancer patients","volume":"34","author":"Tolia","year":"2014","journal-title":"Anticancer Res"},{"key":"2024020319041626500_jbmr2490-bib-0002","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.jsbmb.2013.09.008","article-title":"Prevention and treatment of postmenopausal osteoporosis","volume":"142","author":"Tella","year":"2014","journal-title":"J Steroid Biochem Mol 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