Denosumab Therapy Duration and Osteonecrosis of the Jaw and Skeletal Events in Bone-Metastatic Prostate Cancer
11 affiliations
- 1Division of Medical Hemato-oncology, Department of Internal Medicine, Bucheon St Mary’s Hospital, The Catholic University of Korea, Bucheon, Republic of Korea
- 2Cancer Research Institute, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
- 3Division of Data Science, PIPET (Pharmacometrics Institute for Practical Education and Training), The Catholic University of Korea, Seoul, Republic of Korea
- 4Department of Pharmacology, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
- 5Division of Cardiology, Department of Internal Medicine, Uijeongbu St Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
- 6Catholic Research Institute for Intractable Cardiovascular Disease, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
- 7Department of Oral and Maxillofacial Surgery, School of Medicine, Ewha Woman’s University, Seoul, Republic of Korea
- 8Department of Dentistry, Bucheon St Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
- 9Division of Medical Oncology, Department of Internal Medicine, The Catholic University of Korea, Seoul St Mary’s Hospital, Seoul, Republic of Korea
- 10Department of Hematology, Seoul St Mary’s Hematology Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
- 11Catholic Research Network for Multiple Myeloma, Seoul, Republic of Korea
Abstract
Importance: 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.
Objective: To evaluate the association between duration of denosumab treatment and the 3-year cumulative incidence of ONJ and skeletal events.
Design, Setting, and Participants: 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.
Exposures: Six strategies defined by 3 durations (≤6, 7-12, and ≥13 months), each as a schedule-flexible group and a schedule-adherent subgroup (intervals ≤12 weeks).
Main Outcomes and Measures: 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.
Results: 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, −1.03 to 1.31] percentage points).
Conclusions and Relevance: 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.
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BibTeX
@article{kim2026denosumab,
title = {{Denosumab Therapy Duration and Osteonecrosis of the Jaw and Skeletal Events in Bone-Metastatic Prostate Cancer}},
author = {Seoree Kim and Seungpil Jung and Seonghyeon Bu and Jin Woo Kim and Sung Woon Pyo and Guk Jin Lee and Sang Hoon Chun and In-Ho Kim and Sung-Soo Park and Suein Choi},
journal = {JAMA Network Open},
year = {2026},
month = oct,
doi = {10.1001/jamanetworkopen.2026.39765},
url = {https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2855573},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Denosumab Therapy Duration and Osteonecrosis of the Jaw and Skeletal Events in Bone-Metastatic Prostate Cancer
AU - Seoree Kim
AU - Seungpil Jung
AU - Seonghyeon Bu
AU - Jin Woo Kim
AU - Sung Woon Pyo
AU - Guk Jin Lee
AU - Sang Hoon Chun
AU - In-Ho Kim
AU - Sung-Soo Park
AU - Suein Choi
PY - 2026
DA - 2026/10/21
JO - JAMA Network Open
DO - 10.1001/jamanetworkopen.2026.39765
UR - https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2855573
AB - Importance: 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. Objective: To evaluate the association between duration of denosumab treatment and the 3-year cumulative incidence of ONJ and skeletal events. Design, Setting, and Participants: 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. Exposures: Six strategies defined by 3 durations (≤6, 7-12, and ≥13 months), each as a schedule-flexible group and a schedule-adherent subgroup (intervals ≤12 weeks). Main Outcomes and Measures: 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. Results: 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, −1.03 to 1.31] percentage points). Conclusions and Relevance: 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.
SN - 2574-3805
ER -