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. 2025 Jul 19.
doi: 10.1111/bju.16860. Online ahead of print.

Clinical features of medication-related osteonecrosis of the jaw in prostate cancer management

Yuma Goto #  1   2 , Fumihiko Urabe #  1   2 , Yue Ogihara  1   2 , Mana Nakata  1   2 , Juria Nakano  3 , Kensuke Fujiwara  4 , Masaki Hashimoto  1   5 , Yuhei Koike  1 , Yuya Iwamoto  1   6 , Keiichiro Miyajima  1 , Wataru Fukuokaya  1 , Kosuke Iwatani  1   7 , Yu Imai  1 , Yuzo Inaba  8 , Kagenori Ito  1 , Takafumi Yanagisawa  1 , Masaya Murakami  8 , Kojiro Tashiro  6 , Katsuhito Watanabe  9 , Jun Miki  1   7 , Takahiro Kimura  1 ; JIKEI‐YAYOI Collaborative Group
Affiliations

Clinical features of medication-related osteonecrosis of the jaw in prostate cancer management

Yuma Goto et al. BJU Int. .

Abstract

Objective: To evaluate the cumulative incidence of medication-related osteonecrosis of the jaw (MRONJ) in patients with prostate cancer and bone metastases receiving long-term denosumab treatment, and also the occurrence of severe MRONJ and risk factors associated with the development of both MRONJ and severe MRONJ.

Patients and methods: This retrospective study included 624 patients with prostate cancer and bone metastases treated with denosumab between January 2015 and December 2024. Patients without bone metastasis or with insufficient clinical data were excluded. The study assessed the cumulative incidence of MRONJ, as well as risk factors associated with MRONJ of any stage and severe MRONJ (Stage ≥2). Cox regression analysis was used to identify independent risk factors.

Results: The cumulative incidence of MRONJ at 1, 2, 3, and 6 years was 4.6%, 9.6%, 20.3%, and 51.9%, respectively. For severe MRONJ, the corresponding rates were 2.4%, 6.7%, 13.1%, and 27.9%, respectively. Multivariate analysis identified the following independent risk factors for MRONJ: extent of disease grade ≥3 (hazard ratio [HR] 2.00, P = 0.009), use of anticoagulants and/or antiplatelets (HR 2.08, P = 0.026), and a history of dental treatment within the past 6 months (HR 2.29, P = 0.003). Denosumab administration at intervals >1 month was associated with a reduced risk (HR 0.46, P = 0.041).

Conclusion: This study demonstrates that long-term denosumab treatment in patients with prostate cancer and bone metastases is associated with a substantial cumulative incidence of MRONJ. Key risk factors were identified, along with a modifiable factor that may reduce risk. These findings suggest that adjusting denosumab dosing schedules could help mitigate MRONJ risk, underscoring the need for personalised treatment plans and early preventive strategies.

Keywords: JIKEI‐YAYOI; MRONJ; denosumab; mCRPC; mCSPC; medication‐related osteonecrosis of the jaw; prostate cancer.

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