{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T13:36:29Z","timestamp":1790775389079,"version":"4.1.0"},"reference-count":59,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2018,9,5]],"date-time":"2018-09-05T00:00:00Z","timestamp":1536105600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"},{"start":{"date-parts":[[2018,9,24]],"date-time":"2018-09-24T00:00:00Z","timestamp":1537747200000},"content-version":"vor","delay-in-days":19,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 DE019465"],"award-info":[{"award-number":["R01 DE019465"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["asbmr.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2019,1,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:sec>\n                  <jats:title>\u2003<\/jats:title>\n                  <jats:p>Antiresorptive agents, such as bisphosphonates and denosumab, are frequently used for the management of osteoporosis. Indeed, both medications decrease the risk of osteoporotic fractures; however, these medications are associated with rare but potentially severe side effects, such as osteonecrosis of the jaw (ONJ). ONJ, defined as an area of exposed bone in the maxillofacial region that lasts for 8 weeks, often presents with significant pain and infection and can lead to serious complications. Interestingly, other treatments for osteoporosis have been developed, such as antibodies against the osteocyte-secreted protein, sclerostin. Sclerostin functions to inhibit the Wnt signaling cascade, leading to inhibition of bone formation. In clinical trials, a sclerostin antibody (romosozumab, Amgen Inc., UCB Brussels) increases bone formation and lowers the risk of osteoporotic fractures. However, in conjunction with increased osteoblastic activity, a reduction in bone resorption markers is observed. This antiresorptive effect raises the concern of possible ONJ development in patients treated with sclerostin antibodies. Here, utilizing ligature-induced experimental periodontitis (EP), we evaluated the effects of sclerostin inhibition on the development of ONJ-like lesions in ovariectomized rats. Beginning 8 weeks post-ovariectomy, rats were treated for 22 weeks with weekly injections of vehicle (Veh), 200\u2009\u03bcg\/kg zoledronic acid (ZA), a potent bisphosphonate at 100-fold the osteoporosis dose, or 5\u2009mg\/kg sclerostin antibody (Scl-Ab) at the osteoporotic dose. EP was initiated at week 12 and maintained for the remainder of the study. Scl-Ab treatment transiently increased serum P1NP, a bone formation marker, increased BV\/TV, and decreased eroded surfaces in lumbar vertebrae. ZA-treated rats developed histologic features of ONJ, whereas Veh-treated controls did not. Scl-Ab animals lost less periodontal bone in sites with EP. However, these animals presented with no histologic signs of ONJ. In conclusion, sclerostin inhibition enhanced structural bone parameters, without inducing ONJ-like lesions, in ovariectomized rats with EP. \u00a9 2018 American Society for Bone and Mineral Research.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1002\/jbmr.3581","type":"journal-article","created":{"date-parts":[[2018,9,5]],"date-time":"2018-09-05T17:16:03Z","timestamp":1536167763000},"page":"171-181","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["Clinically Relevant Doses of Sclerostin Antibody Do Not Induce Osteonecrosis of the Jaw (ONJ) in Rats with Experimental Periodontitis"],"prefix":"10.1093","volume":"34","author":[{"given":"Danny","family":"Hadaya","sequence":"first","affiliation":[{"name":"Division of Diagnostic and Surgical SciencesUCLA School of DentistryLos AngelesCAUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ioannis","family":"Gkouveris","sequence":"additional","affiliation":[{"name":"Division of Diagnostic and Surgical SciencesUCLA School of DentistryLos AngelesCAUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akrivoula","family":"Soundia","sequence":"additional","affiliation":[{"name":"Division of Diagnostic and Surgical SciencesUCLA School of DentistryLos AngelesCAUSA"}],"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":"Rogely W","family":"Boyce","sequence":"additional","affiliation":[{"name":"Comparative Biology and Safety SciencesAmgen Inc.Thousand OaksCAUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Stolina","sequence":"additional","affiliation":[{"name":"Discovery Research DepartmentAmgen Inc.Thousand OaksCAUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denise","family":"Dwyer","sequence":"additional","affiliation":[{"name":"Discovery Research DepartmentAmgen Inc.Thousand OaksCAUSA"}],"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":"Flavia Q","family":"Pirih","sequence":"additional","affiliation":[{"name":"Division of Constitutive and Regenerative SciencesUCLA School of DentistryLos AngelesCAUSA"}],"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":"Division of Diagnostic and Surgical SciencesUCLA School of DentistryLos AngelesCAUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2018,9,5]]},"reference":[{"issue":"11","key":"2024021014533592500_jbmr3581-bib-0001","doi-asserted-by":"crossref","first-page":"2520","DOI":"10.1002\/jbmr.2269","article-title":"The recent prevalence of osteoporosis and low bone mass in the United States based on bone mineral density at the femoral neck or lumbar spine","volume":"29","author":"Wright","year":"2014","journal-title":"J Bone Miner 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