{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T11:13:32Z","timestamp":1780398812888,"version":"3.54.1"},"reference-count":98,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T00:00:00Z","timestamp":1779667200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"European Regional Fund"},{"name":"Croatian Ministry of Science, Infrastructural Project","award":["KK.01.1.1.02.0015"],"award-info":[{"award-number":["KK.01.1.1.02.0015"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background\/Objectives: Postmenopausal osteoporosis is associated with systemic metabolic alterations related to estrogen deficiency. This exploratory study investigated the early metabolic, oxidative, and histomorphological effects of alendronate, a standardized hop extract, and their combination in ovariectomized (OV) rats. Methods: Female Wistar rats (n = 70) were randomly allocated to seven groups: six OV groups or a sham-operated control (n = 10 per group). Following a 30-day postoperative period for model development, animals received daily treatment for 2 weeks with vehicle (placebo), low- or high-dose alendronate (1 and 2 mg\/kg, respectively), standardized hop extract (60 mg\/kg), or both. Oxidative stress markers, liver and perigonadal adipose tissue histology, and tissue metabolism were assessed. Results: No evidence of adverse hepatic, renal, or systemic effects was observed. Oxidative damage markers remained largely unchanged, although ovariectomy was associated with reduced hepatic catalase activity, which was increased by high-dose alendronate. Treatment-related morphological changes in adipose tissue were observed. Serum triglyceride levels were unaffected, whereas total cholesterol was significantly increased in animals receiving hop extract. Hepatic triglyceride levels were influenced by alendronate treatment, modified by hop extract. MALDI-TOF MS suggested no OV-related alterations in amino acid, lipid, steroid, and redox-related metabolism in liver and adipose tissue. The subsequent treatments, especially in the high-dose alendronate group and hop-extract group, partially modified these metabolic signatures; however, these findings remain provisional pending MS\/MS validation. Conclusions: Most outcomes were not significantly altered by OV. Alendronate and hop extract exert distinct short-term effects on selected metabolic and oxidative parameters in this exploratory model. Further studies are needed to investigate translational potential.<\/jats:p>","DOI":"10.3390\/nu18111685","type":"journal-article","created":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T14:10:22Z","timestamp":1779718222000},"page":"1685","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Early Metabolic and Oxidative Effects of Hop Extract, Alendronate, and Their Combination Across Tissues in an Estrogen-Deficient Rat Model: An Exploratory Study"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7814-2031","authenticated-orcid":false,"given":"Edi","family":"Ro\u0111ak","sequence":"first","affiliation":[{"name":"Department of Histology and Embryology, Faculty of Medicine Osijek, University of Osijek, J. Huttlera 4, 31000 Osijek, Croatia"},{"name":"Department of Medicine, University of Connecticut Health Centre, 263 Farmington Ave., Farmington, CT 06030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9587-5413","authenticated-orcid":false,"given":"Nika","family":"Srb","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology, Faculty of Medicine Osijek, University of Osijek, J. Huttlera 4, 31000 Osijek, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9589-1472","authenticated-orcid":false,"given":"Robert","family":"Grgac","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology, Faculty of Medicine Osijek, University of Osijek, J. Huttlera 4, 31000 Osijek, Croatia"},{"name":"Department of Clinical Laboratory Diagnostics, University Hospital Centre Osijek, J. Huttlera 4, 31000 Osijek, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u017deljko","family":"Debeljak","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory Diagnostics, University Hospital Centre Osijek, J. Huttlera 4, 31000 Osijek, Croatia"},{"name":"Department of Pharmacology, Faculty of Medicine Osijek, University of Osijek, J. Huttlera 4, 31000 Osijek, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivana","family":"Ili\u0107","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology, Faculty of Medicine Osijek, University of Osijek, J. Huttlera 4, 31000 Osijek, Croatia"},{"name":"Department of Anatomy, Histology, Embryology, Pathological Anatomy and Pathological Histology, Faculty of Dental Medicine and Health, University of Osijek, Crkvena 21, 31000 Osijek, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5102-3606","authenticated-orcid":false,"given":"Nada","family":"Or\u0161oli\u0107","sequence":"additional","affiliation":[{"name":"Department of Animal Physiology, Faculty of Science Zagreb, University of Zagreb, Rooseveltov trg 6, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4136-820X","authenticated-orcid":false,"given":"Nikola","family":"Bijeli\u0107","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology, Faculty of Medicine Osijek, University of Osijek, J. Huttlera 4, 31000 Osijek, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,25]]},"reference":[{"key":"ref_1","unstructured":"Feingold, K.R., Ahmed, S.F., Anawalt, B., Blackman, M.R., Boyce, A., Chrousos, G., Corpas, E., de Herder, W.W., Dhatariya, K., and Dungan, K. (2000). The Epidemiology and Pathogenesis of Osteoporosis. Endotext, MDText.com, Inc."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1007\/s43465-023-01058-3","article-title":"Classification of Osteoporosis","volume":"57","author":"Amarnath","year":"2023","journal-title":"Indian J. Orthop."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Wang, L.-T., Chen, L.-R., and Chen, K.-H. (2023). Hormone-Related and Drug-Induced Osteoporosis: A Cellular and Molecular Overview. Int. J. Mol. 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