{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T14:45:26Z","timestamp":1793371526477,"version":"4.5.0"},"reference-count":33,"publisher":"American Medical Association (AMA)","issue":"10","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Netw Open"],"abstract":"\n Importance<\/jats:title>\n Denosumab reduces skeletal-related events in bone-metastatic prostate cancer but carries a cumulative risk of medication-related osteonecrosis of the jaw (ONJ). The treatment duration that best balances these risks has not been established in clinical settings.<\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n To evaluate the association between duration of denosumab treatment and the 3-year cumulative incidence of ONJ and skeletal events.<\/jats:p>\n <\/jats:sec>\n \n Design, Setting, and Participants<\/jats:title>\n This nationwide retrospective cohort study emulated a target trial using Korean Health Insurance Review and Assessment Service data from January 1, 2009, through August 31, 2024; patients were not randomized. A clone-censor-weight approach with inverse probability of censoring weighting estimated 3-year cumulative incidence and risk ratios (RRs), with death as a competing event. Men included in the analysis had bone-metastatic castration-resistant prostate cancer and initiated oncologic-dose denosumab therapy; men with castration-sensitive disease were excluded.<\/jats:p>\n <\/jats:sec>\n \n Exposures<\/jats:title>\n Six strategies defined by 3 durations (\u22646, 7-12, and \u226513 months), each as a schedule-flexible group and a schedule-adherent subgroup (intervals \u226412 weeks).<\/jats:p>\n <\/jats:sec>\n \n Main Outcomes and Measures<\/jats:title>\n Three-year cumulative incidence of ONJ and skeletal events (pathologic fracture, spinal cord compression, and surgery to bone) was the primary outcome; a radiotherapy-inclusive conventional composite of skeletal-related events was assessed as a secondary outcome.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n Among 3307 men included in the analysis (mean [SD] age, 72.6 [8.6] years; median follow-up, 42.6 [IQR, 26.5-57.4] months), the overall 3-year cumulative incidence was 9.8% (95% CI, 8.7%-11.0%) for ONJ and 4.9% (95% CI, 4.2%-5.7%) for skeletal events. Relative to treatment for 6 months or less, treatment for 7 to 12 months showed a lower risk of skeletal events (3.82% [95% CI, 3.04%-4.80%] vs 5.76% [95% CI, 4.23%-7.79%]; RR, 0.66 [95% CI, 0.45-0.97]) and higher risk of ONJ (3.28% [95% CI, 2.41%-4.44%] vs 1.47% [95% CI, 0.86%-2.50%]; RR, 2.22 [95% CI, 1.21-4.11]). Compared with 7 to 12 months, treatment for 13 months or longer was associated with higher risk of ONJ (12.20% [95% CI, 10.86%-13.68%]; risk difference, 8.93 [95% CI, 7.16-10.64] percentage points), without further reduction in risk for skeletal events (3.99% [95% CI, 3.30%-4.82%]; risk difference, 0.17 [95% CI, \u22121.03 to 1.31] percentage points).<\/jats:p>\n <\/jats:sec>\n \n Conclusions and Relevance<\/jats:title>\n In this cohort study of bone-metastatic castration-resistant prostate cancer, denosumab treatment for 7 to 12 months was associated with lower risk of skeletal events and a modest increase in ONJ, whereas treatment beyond 12 months was associated with markedly higher ONJ risk but no further reduction of skeletal events. These findings support individualized reassessment of denosumab treatment duration after approximately 1 year.<\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jamanetworkopen.2026.39765","type":"journal-article","created":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T15:00:38Z","timestamp":1792594838000},"page":"e2639765","source":"Crossref","is-referenced-by-count":1,"title":["Denosumab Therapy Duration and Osteonecrosis of the Jaw and Skeletal Events in Bone-Metastatic Prostate Cancer"],"prefix":"10.1001","volume":"9","author":[{"given":"Seoree","family":"Kim","sequence":"first","affiliation":[{"name":"Division of Medical Hemato-oncology, Department of Internal Medicine, Bucheon St Mary\u2019s Hospital, The Catholic University of Korea, Bucheon, Republic of Korea"},{"name":"Cancer Research Institute, College of Medicine, The Catholic University of Korea, Seoul, Republic of 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Woo","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, School of Medicine, Ewha Woman\u2019s University, Seoul, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sung Woon","family":"Pyo","sequence":"additional","affiliation":[{"name":"Department of Dentistry, Bucheon St Mary\u2019s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guk Jin","family":"Lee","sequence":"additional","affiliation":[{"name":"Division of Medical Hemato-oncology, Department of Internal Medicine, Bucheon St Mary\u2019s Hospital, The Catholic University of Korea, Bucheon, Republic of Korea"},{"name":"Cancer Research Institute, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sang 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