{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T11:37:38Z","timestamp":1762861058593,"version":"build-2065373602"},"reference-count":106,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T00:00:00Z","timestamp":1762819200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Background and Objectives: Estrogen deficiency after menopause accelerates bone loss through oxidative stress and inflammatory cytokines. Sodium phenylbutyrate (SP), a histone deacetylase inhibitor, exhibits antioxidative and anti-inflammatory effects, but its impact on postmenopausal osteoporosis remains unclear. Materials and Methods: Thirty female Wistar rats were divided into control, ovariectomy (OVX), and OVX+SPB groups (n = 10 each). After 12 weeks, bone mineral density (BMD), histomorphometry, bone marrow biomarkers (MDA, TNF-\u03b1, IL-6, RANKL), and plasma Cathepsin K were evaluated. Results: OVX induced trabecular deterioration with reduced number, area, and thickness (all p &lt; 0.001), increased separation (p &lt; 0.001), and decreased femoral and lumbar BMD (p &lt; 0.001). SPB significantly improved these indices (TN, p &lt; 0.05; TA, p &lt; 0.01; TH, p &lt; 0.05; femoral BMD, p &lt; 0.05; lumbar BMD, p &lt; 0.001; TS, p = 0.001). OVX elevated MDA, TNF-\u03b1, IL-6, RANKL, and Cathepsin K (all p &lt; 0.001), which were significantly reduced by SPB (MDA, p &lt; 0.001; TNF-\u03b1, p &lt; 0.01; IL-6, p &lt; 0.01; RANKL, p &lt; 0.001; Cathepsin K, p &lt; 0.001). Conclusions: SPB mitigates OVX-induced oxidative stress, inflammatory cytokine release, and osteoclast-mediated resorption, resulting in partial but significant improvements across biochemical, structural, and histomorphometric parameters in estrogen-deficient rats. Given its established clinical safety profile, SPB emerges as a cost-effective candidate for repurposing in postmenopausal osteoporosis, warranting further translational and clinical studies.<\/jats:p>","DOI":"10.3390\/medicina61112016","type":"journal-article","created":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T10:56:27Z","timestamp":1762858587000},"page":"2016","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Sodium Phenylbutyrate Ameliorates Ovariectomy-Induced Bone Loss in Rats"],"prefix":"10.3390","volume":"61","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2480-1374","authenticated-orcid":false,"given":"Bakiye","family":"Akba\u015f","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, Faculty of Medicine, Karadeniz Technical University, 61080 Trabzon, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6513-0656","authenticated-orcid":false,"given":"G\u00fclseren","family":"Din\u00e7","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Faculty of Medicine, Karadeniz Technical University, 61080 Trabzon, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6333-4919","authenticated-orcid":false,"given":"Ahmet","family":"Akba\u015f","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Faculty of Medicine, Karadeniz Technical University, 61080 Trabzon, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3906-2538","authenticated-orcid":false,"given":"Nadir Adnan","family":"Hac\u0131m","sequence":"additional","affiliation":[{"name":"Department of General Surgery, G\u00fcne\u015fli Erdem Hospital, 34212 Istanbul, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8420-9298","authenticated-orcid":false,"given":"G\u00fcl\u00e7in","family":"Ercan","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Sultan 2. Abdulhamid Han Educational and Research Hospital, Istanbul Provincial Directorate of Health, 34668 Istanbul, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4272-0562","authenticated-orcid":false,"given":"Hatice","family":"Ayg\u00fcn","sequence":"additional","affiliation":[{"name":"Neuroscience Laboratory, BAMER, Biruni University, 34015 Istanbul, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5427-8428","authenticated-orcid":false,"given":"Oytun","family":"Erba\u015f","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, BAMER, Biruni University, 34015 Istanbul, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Shen, Y., Huang, X., Wu, J., Lin, X., Zhou, X., Zhu, Z., and Shan, P.F. (2022). 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