{"doi":"10.1016/j.apsb.2025.07.035","title":"Dissecting the effects of 223Radium on the bone microenvironment","abstract":"Radium-223 ( 223 Ra) is a bone-seeking, alpha-particle-emitting radionuclide that is approved for the treatment of patients with metastatic prostate cancer and is currently being tested in clinical trials for primary and metastatic cancers to the bone. 223 Ra accumulates in mineralized bone areas with high bone turnover, where its effects are confined within 100 μm of the bone–marrow interface due to the short tissue penetrance of the alpha particles. A recent clinical study has shown a significantly increased fracture rate associated with the administration of 223 Ra, mostly in tumor-free bones. Importantly, the biological mechanisms underlying this bone fragility remain unclear. In this work, we combined micro-computed tomography and mechanical studies with ex vivo spatial biology analysis based on 3D fluorescence microscopy to clarify the effects of 223 Ra on bone and key bone stromal cell components. We found that 223 Ra caused major trabecular bone loss with no detectable impact on cortical bone. In addition, 223 Ra impaired osteoblast bone-forming activity, which was paralleled by a transient increase in osteoclast number and long-term adipocyte formation. Overall, these results suggest that the impact of 223 Ra on bone health is orchestrated by multiple bone stromal cell components. 223 Ra-mediated trabecular bone loss was prevented by administration of zoledronic acid, which should always be combined with 223 Ra.","journal":"Acta Pharmaceutica Sinica B","year":2025,"id":532718,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9636,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1414239,"name":"Elisa Serafini","orcid":"0009-0005-4070-1244","position":1,"is_corresponding":false},{"id":1414712,"name":"Ludovica La Posta","orcid":null,"position":2,"is_corresponding":false},{"id":1249227,"name":"D. Nicole Meyers","orcid":null,"position":3,"is_corresponding":false},{"id":1414240,"name":"Nicholas J. Dunbar","orcid":"0000-0001-7769-4176","position":4,"is_corresponding":false},{"id":413097,"name":"Paul G. Corn","orcid":"0000-0002-4106-6335","position":5,"is_corresponding":false},{"id":744995,"name":"Florent Elefteriou","orcid":"0000-0002-2972-5633","position":6,"is_corresponding":false},{"id":339396,"name":"Catherine G. Ambrose","orcid":"0000-0002-3866-0683","position":7,"is_corresponding":false},{"id":317156,"name":"Stefano Casarin","orcid":"0000-0002-7416-2366","position":8,"is_corresponding":false},{"id":258170,"name":"Antonios G. Mikos","orcid":"0000-0002-0709-990X","position":9,"is_corresponding":false},{"id":403010,"name":"Eleonora Dondossola","orcid":"0000-0001-6916-5418","position":10,"is_corresponding":false},{"id":685018,"name":"Sergio Barrios","orcid":"0000-0003-0364-2466","position":0,"is_corresponding":true}],"reference_count":46,"raw_metadata":null,"created_at":"2026-07-19T02:51:27.893975Z","pmid":"41132855","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}