{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T18:07:00Z","timestamp":1788804420625,"version":"build-2803163510"},"reference-count":38,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2024,7,21]],"date-time":"2024-07-21T00:00:00Z","timestamp":1721520000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institutes of Health\/National Cancer Institute","award":["R01CA174798"],"award-info":[{"award-number":["R01CA174798"]}]},{"name":"National Institutes of Health\/National Cancer Institute","award":["5P50CA140388"],"award-info":[{"award-number":["5P50CA140388"]}]},{"name":"National Institutes of Health\/National Cancer Institute","award":["P30CA16672"],"award-info":[{"award-number":["P30CA16672"]}]},{"name":"National Institutes of Health\/National Cancer Institute","award":["RP190252"],"award-info":[{"award-number":["RP190252"]}]},{"name":"National Institutes of Health\/National Cancer Institute","award":["RP230247"],"award-info":[{"award-number":["RP230247"]}]},{"name":"Cancer Prevention Research Institute of Texas","award":["R01CA174798"],"award-info":[{"award-number":["R01CA174798"]}]},{"name":"Cancer Prevention Research Institute of Texas","award":["5P50CA140388"],"award-info":[{"award-number":["5P50CA140388"]}]},{"name":"Cancer Prevention Research Institute of Texas","award":["P30CA16672"],"award-info":[{"award-number":["P30CA16672"]}]},{"name":"Cancer Prevention Research Institute of Texas","award":["RP190252"],"award-info":[{"award-number":["RP190252"]}]},{"name":"Cancer Prevention Research Institute of Texas","award":["RP230247"],"award-info":[{"award-number":["RP230247"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Radium 223 (Ra-223) is an \u03b1-emitting bone-homing radiopharmaceutical that targets tumor-induced osteoblasts and is used to reduce bone pain and prolong overall survival in men with bone-metastatic, castrate-resistant prostate cancer. However, increased fracture risk in skeletal sites with no bone metastasis has been observed in patients treated with Ra-223. Both luciferase- or green fluorescence protein (GFP)-labeled osteoblast reporter mice were used to monitor the effect of Ra-223 on resident osteoblasts and normal bone structure. Upon Ra-223 treatment, 70% of resident osteoblasts were reduced within 2 days, and the osteoblast reduction lasted for at least 18 weeks without detectable recovery, as measured by in vivo bioluminescent imaging. In GFP-labeled osteoblast reporter mice, Ra-223 mainly reduced osteoblasts localized in the trabecular bone areas; the osteoblasts in the growth plates were less affected. Micro-computed tomography analyses showed that Ra-223 significantly reduced bone mineral density and bone microstructure in the trabecular area of femurs but not in the cortical bone. Tumor-induced bone was generated by inoculating osteogenic TRAMP-BMP4 prostate cancer cells into the mouse femurs; Ra-223 treatment significantly reduced tumor-induced osteoblasts. Our study shows that Ra-223 affects bone structures that are not involved in bone metastasis. Strategies that improve bone health may reduce fracture risk in patients receiving Ra-223.<\/jats:p>","DOI":"10.3390\/cancers16142603","type":"journal-article","created":{"date-parts":[[2024,7,22]],"date-time":"2024-07-22T12:20:38Z","timestamp":1721650838000},"page":"2603","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Radium-223 Treatment Produces Prolonged Suppression of Resident Osteoblasts and Decreased Bone Mineral Density in Trabecular Bone in Osteoblast Reporter Mice"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1763-1303","authenticated-orcid":false,"given":"Song-Chang","family":"Lin","sequence":"first","affiliation":[{"name":"Department of Translational Molecular Pathology, MD Anderson Cancer Center, University of Texas, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoyu","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Translational Molecular Pathology, MD Anderson Cancer Center, University of Texas, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul G.","family":"Corn","sequence":"additional","affiliation":[{"name":"Department of Genitourinary Medical Oncology, MD Anderson Cancer Center, University of Texas, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jossana","family":"Damasco","sequence":"additional","affiliation":[{"name":"Department of Interventional Radiology, MD Anderson Cancer Center, University of Texas, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Chen","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Translational Molecular Pathology, MD Anderson Cancer Center, University of Texas, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian H.","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Genitourinary Medical Oncology, MD Anderson Cancer Center, University of Texas, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8645-6890","authenticated-orcid":false,"given":"Nora M.","family":"Navone","sequence":"additional","affiliation":[{"name":"Department of Genitourinary Medical Oncology, MD Anderson Cancer Center, University of Texas, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher J.","family":"Logothetis","sequence":"additional","affiliation":[{"name":"Department of Genitourinary Medical Oncology, MD Anderson Cancer Center, University of Texas, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7447-0705","authenticated-orcid":false,"given":"Marites P.","family":"Melancon","sequence":"additional","affiliation":[{"name":"Department of Interventional Radiology, MD Anderson Cancer Center, University of Texas, Houston, TX 77030, USA"},{"name":"UTHealth Houston Graduate School of Biomedical Sciences, MD Anderson Cancer Center, University of Texas, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5754-6950","authenticated-orcid":false,"given":"Theocharis","family":"Panaretakis","sequence":"additional","affiliation":[{"name":"Department of Genitourinary Medical Oncology, MD Anderson Cancer Center, University of Texas, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sue-Hwa","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Translational Molecular Pathology, MD Anderson Cancer Center, University of Texas, Houston, TX 77030, USA"},{"name":"Department of Genitourinary Medical Oncology, MD Anderson Cancer Center, University of Texas, Houston, TX 77030, USA"},{"name":"UTHealth Houston Graduate School of Biomedical Sciences, MD Anderson Cancer Center, University of Texas, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,7,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1053\/hp.2000.6698","article-title":"Metastatic patterns of prostate cancer: An autopsy study of 1589 patients","volume":"31","author":"Bubendorf","year":"2000","journal-title":"Hum. 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