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However, this increases the risk of medication-related osteonecrosis of the jaw (MRONJ). The safety of long-term BMA administration in clinical practice remains unclear. We aimed to determine the cumulative incidence and risk factors of MRONJ. One hundred and seventy-nine patients with prostate cancer with bone metastases treated with BMA at our institution since 2008 were included in this study. Twenty-seven patients (15%) had MRONJ during the follow-up period (median, 19\u00a0months; interquartile range, 9\u201343\u00a0months). The 2-year, 5-year, and 10-year cumulative MRONJ incidence rates were 18%, 27%, and 61%, respectively. Multivariate analysis identified denosumab use as a risk factor for MRONJ, compared with zoledronic acid use (HR 4.64, 95% CI 1.93\u201311.1). Additionally, BMA use at longer than one-month intervals was associated with a lower risk of MRONJ (HR 0.08, 95% CI 0.01\u20130.64). Furthermore, six or more bone metastases (HR 3.65, 95% CI 1.13\u201311.7) and diabetes mellitus (HR 5.07, 95% CI 1.68\u201315.2) were risk factors for stage 2 or more severe MRONJ. MRONJ should be considered during long-term BMA administration in prostate cancer patients with bone metastases.<\/jats:p>","DOI":"10.1038\/s41598-024-64440-7","type":"journal-article","created":{"date-parts":[[2024,6,11]],"date-time":"2024-06-11T19:03:07Z","timestamp":1718132587000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Cumulative incidence and risk factors for medication-related osteonecrosis of the jaw during long-term prostate cancer management"],"prefix":"10.1038","volume":"14","author":[{"given":"Masaru","family":"Tani","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8409-5152","authenticated-orcid":false,"given":"Koji","family":"Hatano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akihiro","family":"Yoshimura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuki","family":"Horibe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yutong","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nesrine","family":"Sassi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshiki","family":"Oka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yohei","family":"Okuda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akinaru","family":"Yamamoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshihiro","family":"Uemura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaku","family":"Yamamichi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Ishizuya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshiyuki","family":"Yamamoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taigo","family":"Kato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsunari","family":"Kawashima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norio","family":"Nonomura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,6,11]]},"reference":[{"key":"64440_CR1","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1007\/s00774-020-01151-9","volume":"39","author":"Y Nakai","year":"2021","unstructured":"Nakai, Y. et al. Antiresorptive agent-related osteonecrosis of the jaw in prostate cancer patients with bone metastasis treated with bone-modifying agents. J. Bone Miner. Metab. 39, 295\u2013301 (2021).","journal-title":"J. Bone Miner. Metab."},{"key":"64440_CR2","unstructured":"National Comprehensive Cancer Network (2019) NCCN clinical practice guidelines in oncology prostate cancer version 4."},{"key":"64440_CR3","doi-asserted-by":"publisher","first-page":"1115","DOI":"10.1016\/S0278-2391(03)00720-1","volume":"61","author":"R Marx","year":"2003","unstructured":"Marx, R. Pamidronate (Aredia) and zoledronate (Zometa) induced avascular necrosis of the jaws: A growing epidemic. J. Oral Maxillofac. Surg. 61, 1115\u20131117 (2003).","journal-title":"J. Oral Maxillofac. Surg."},{"key":"64440_CR4","doi-asserted-by":"publisher","first-page":"161","DOI":"10.5794\/jjoms.68.161","volume":"68","author":"H Kishimoto","year":"2022","unstructured":"Kishimoto, H. & Kurita, H. 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