{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T18:59:12Z","timestamp":1785437952077,"version":"3.56.0"},"reference-count":32,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T00:00:00Z","timestamp":1777507200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Medical University\u2013Plovdiv","award":["BG-RRP-2.004-0007-C01."],"award-info":[{"award-number":["BG-RRP-2.004-0007-C01."]}]},{"award":["BG-RRP-2.004-0007-C01."],"award-info":[{"award-number":["BG-RRP-2.004-0007-C01."]}],"id":[{"id":"https:\/\/ror.org\/02kzxd152","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background\/Objectives: Anthracyclines such as doxorubicin (DOX) are integral to pediatric cancer protocols, yet little is known about how juvenile DOX exposure shapes the long-term trajectory of bone growth, microarchitectural connectivity, and the functional balance of bone turnover after treatment cessation. This study aimed to define how juvenile DOX exposure remodels trabecular architecture and bone homeostasis both acutely and after recovery. Methods: Four-week-old female BALB\/c mice were treated with 6 mg\/kg DOX or saline once weekly for four weeks. Bone parameters were analyzed immediately after treatment and after a 4-week drug-free recovery period. Assessments included high-resolution \u00b5CT for bone structure and connectivity, H&amp;E and TRAP staining for histological evaluation, and ELISA for bone turnover markers (PINP, OC\/BGP, TRACP-5b) in both serum and bone marrow. Results: DOX exposure significantly compromised trabecular bone mass and network connectivity, with persistent bone loss extending into the recovery period. Histologically, DOX caused marked degeneration in the epiphyseal growth plate and calcified zones, alongside a marked increase in osteoclast numbers. Functionally, an acute increase in circulating bone formation markers was observed post-treatment. However, during the recovery phase, this transitioned to a significant suppression of these systemic markers, coupled with significantly increased localized bone resorption. Conclusions: Juvenile DOX exposure produces sustained trabecular network impairment and growth plate degeneration. This durable structural deterioration is functionally associated with the establishment of a localized, pathologically uncoupled remodeling environment.<\/jats:p>","DOI":"10.3390\/cancers18091438","type":"journal-article","created":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T12:20:25Z","timestamp":1777551625000},"page":"1438","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Juvenile Doxorubicin Exposure Causes Lasting Trabecular Bone Loss in Mice: A Preclinical Model of Long-Term Skeletal Damage"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8371-6239","authenticated-orcid":false,"given":"Veli Kaan","family":"Ayd\u0131n","sequence":"first","affiliation":[{"name":"Department of Biophysics, Faculty of Medicine, Pamukkale University, 20160 Denizli, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aliye","family":"Uysal","sequence":"additional","affiliation":[{"name":"Department of Histology, Faculty of Medicine, Pamukkale University, 20160 Denizli, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G\u00fcl\u00e7in","family":"Abban Mete","sequence":"additional","affiliation":[{"name":"Department of Histology, Faculty of Medicine, Pamukkale University, 20160 Denizli, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0997-1439","authenticated-orcid":false,"given":"Gergana","family":"Lengerova","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Immunology \u201cProf. Dr. Elissay Yanev\u201d, Medical University of Plovdiv, 4002 Plovdiv, Bulgaria"},{"name":"Research Institute, Medical University of Plovdiv, 4002 Plovdiv, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Bozhkova","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Immunology \u201cProf. Dr. Elissay Yanev\u201d, Medical University of Plovdiv, 4002 Plovdiv, Bulgaria"},{"name":"Research Institute, Medical University of Plovdiv, 4002 Plovdiv, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0522-5682","authenticated-orcid":false,"given":"Steliyan","family":"Petrov","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Immunology \u201cProf. Dr. Elissay Yanev\u201d, Medical University of Plovdiv, 4002 Plovdiv, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4832-0436","authenticated-orcid":false,"given":"Aylin","family":"K\u00f6seler","sequence":"additional","affiliation":[{"name":"Department of Biophysics, Faculty of Medicine, Pamukkale University, 20160 Denizli, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1007\/s11914-022-00749-4","article-title":"Bone-Muscle Crosstalk: Musculoskeletal Complications of Chemotherapy","volume":"20","author":"Hain","year":"2022","journal-title":"Curr. 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