{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T13:56:34Z","timestamp":1791467794423,"version":"4.3.4"},"reference-count":15,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T00:00:00Z","timestamp":1781481600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"Health Commission of Sichuan Province Medical Science and Technology Program","award":["24CXTD06"],"award-info":[{"award-number":["24CXTD06"]}]},{"DOI":"10.13039\/100012542","name":"Sichuan Province Science and Technology Support Program","doi-asserted-by":"publisher","award":["2026YFHZ0048"],"award-info":[{"award-number":["2026YFHZ0048"]}],"id":[{"id":"10.13039\/100012542","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,10,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To define the time course of fracture risk with radium-223 in combination with androgen receptor pathway inhibitor (ARPi) therapy and assess the clinical impact of concomitant bone-protective agent (BPA) use on mitigating this risk.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>An exploratory person-time approximation approach was used to perform a Bayesian re-analysis of the landmark ERA223 and PEACE-3 clinical trials. In ERA223, we estimated interval-specific fracture incidence rate ratios (IRRs) during follow-up to characterize temporal trajectories. Interval-specific analyses were based on an exploratory person-time approximation approach. In PEACE-3, we used published hazard ratios to re-derive posterior distributions of risk ratios, risk differences, and posterior distributions comparing pre- vs post-mandatory BPA fracture incidences. Posterior distributions were modeled with beta-binomial and gamma-Poisson conjugate priors.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In the ERA223 population, the fracture excess risk peaked during the first year of treatment, with elevated interval-specific IRRs in the 0\u20136\u00a0month and 6\u201312\u00a0month intervals. In PEACE-3, the treatment-induced fracture burden for the radium-223 combination treatments was lower following requirement of BPA, with the risk ratio (RR) falling from 2.54 (95% credible interval [CrI]\u00a0=\u00a01.53\u20134.60) prior to the mandate to 1.46 (95% CrI 0.88\u20132.49) post-implementation. The addition of BPA prophylaxis demonstrated a synergistic protective effect, yielding a more pronounced reduction in fracture risk within the radium-223 combination arm relative to the ARPi-monotherapy group.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Fracture risk was confined to early periods of ERA223 treatment and diminished after the compulsory addition of BPAs in PEACE-3. Due to the limitations of using estimated person-time data and observational comparisons, the findings are best interpreted as descriptive and hypothesis-generating.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jjco\/hyag093","type":"journal-article","created":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T11:15:06Z","timestamp":1779794106000},"page":"1234-1239","source":"Crossref","is-referenced-by-count":0,"title":["Bayesian re-analysis of ERA223 and PEACE-3 temporal dynamics and bone protection in radium-223-treated metastatic castration-resistant prostate cancer"],"prefix":"10.1093","volume":"56","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2275-4527","authenticated-orcid":false,"given":"Wei","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Urology, Zigong Fourth People\u2019s Hospital , Zigong, 1331 Ziwei Rd., Ziliujing Dist., Zigong 643000, Sichuan ,","place":["China"]},{"name":"Department of Urology, Institute of Science Tokyo , 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soichiro","family":"Yoshida","sequence":"additional","affiliation":[{"name":"Department of Urology, Institute of Science Tokyo , 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shugo","family":"Yajima","sequence":"additional","affiliation":[{"name":"Department of Urology, National Cancer Center Hospital East , 6-5-1 Kashiwanoha, Kashiwa, Chiba , 277-8577,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9454-3345","authenticated-orcid":false,"given":"Motohiro","family":"Fujiwara","sequence":"additional","affiliation":[{"name":"Department of Urology, Teikyo University Hospital , Mizonokuchi, 5-1-1 Futago, Takatsu-ku, Kawasaki, Kanagawa , 213-8507,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyuki","family":"Sato","sequence":"additional","affiliation":[{"name":"Department of Clinical Biostatistics, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo , 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akihiro","family":"Hirakawa","sequence":"additional","affiliation":[{"name":"Department of Clinical Biostatistics, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo , 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7548-1580","authenticated-orcid":false,"given":"Hiroshi","family":"Fukushima","sequence":"additional","affiliation":[{"name":"Department of Urology, Institute of Science Tokyo , 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8957-0429","authenticated-orcid":false,"given":"Yosuke","family":"Yasuda","sequence":"additional","affiliation":[{"name":"Department of Urology, Institute of Science Tokyo , 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hajime","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Department of Urology, Institute of Science Tokyo , 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuhisa","family":"Fujii","sequence":"additional","affiliation":[{"name":"Department of Urology, Institute of Science Tokyo , 1-5-45 Yushima, Bunkyo-ku, Tokyo 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