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Rats were assigned into 4 groups: Sham-operated, OVX group, and OVX rats orally treated with sitagliptin (10, 20 mg\/kg), respectively, after 8 weeks of OVX for 4 weeks. Biochemical, real-time polymerase chain reaction, histopathological, and immunohistochemical analyses of bone resorption and formation were conducted. Sitagliptin ameliorated bone mineral density (BMD), restored calcium and phosphorus levels in OVX rats, elevated catalase and decreased malondialdehyde, reduced receptor activator of NF-\u03baB ligand (RANKL), elevated osteoprotegerin (OPG), and reduced tartrate-resistant acid phosphatase (TRAP) femur contents. Sitagliptin mitigated variations in mRNA expressions of RUNX2 and protein kinase B (AKT) in femur tissue. Moreover, sitagliptin reduced caspase-3 protein expression and improved bone histomorphology and mechanical properties. Sitagliptin\u2019s anti-oxidant activity mediated its anti-osteoporotic effect in OVX rats via modulation of RUNX2, downregulation of RANKL\/OPG, AKT pathways, apoptosis, and histomorphometry alterations revealing attenuation of osteoclastogenesis and promotion of osteoblast formation.<\/jats:p>","DOI":"10.1007\/s00210-025-04145-4","type":"journal-article","created":{"date-parts":[[2025,5,21]],"date-time":"2025-05-21T05:41:24Z","timestamp":1747806084000},"page":"15857-15871","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Anti-osteoporotic effect of sitagliptin in an osteoporosis model of ovariectomized rats: role of RUNX2 and RANKL\/OPG ratio"],"prefix":"10.1007","volume":"398","author":[{"given":"Salma Ahmed","family":"El-Marasy","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rehab F.","family":"Abdel-Rahman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reham M.","family":"Abd-Elsalam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanan A.","family":"Ogaly","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rasha M.","family":"Allam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,5,21]]},"reference":[{"key":"4145_CR1","doi-asserted-by":"publisher","first-page":"583","DOI":"10.1111\/jwas.12237","volume":"46","author":"NM Abu-Elala","year":"2015","unstructured":"Abu-Elala NM, Abd-Elsalam RM, Marzouk MS (2015) Molecular and immunohistochemical diagnosis of Photobacterium damselae subspecies piscicida during naturally occurring disease in Egypt. 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