{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T11:51:26Z","timestamp":1781783486806,"version":"3.54.5"},"reference-count":70,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T00:00:00Z","timestamp":1781740800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biology"],"abstract":"<jats:p>This study evaluated the structural, electronic, pharmacokinetic, and receptor-binding properties of three bisphosphonate derivatives, alendronate, risedronate, and zoledronate, to investigate their therapeutic relevance in osteoporosis and breast cancer. Density Functional Theory (DFT) calculations at the B3LYP\/6-31G(d,p) level showed that risedronate exhibited the highest kinetic stability (\u0394E = 6.7468 eV), whereas zoledronate displayed greater chemical reactivity (\u0394E = 2.9669 eV) and the strongest nonlinear optical response (\u03b2 = 1.20 \u00d7 10\u221230 esu). ADMET analysis indicated acceptable safety profiles for all compounds, although high polarity and low lipophilicity may limit oral bioavailability. Molecular docking against 11 breast cancer- and bone metabolism-related targets revealed favorable binding affinities, particularly for zoledronate and risedronate. Zoledronate showed strong interactions with ESR2, VEGFR\/KDR, GGPS1, and FPPS, whereas risedronate exhibited notable affinity for BRCA2 and MMP9. Bioinformatics analyses identified significant dysregulation of GGPS1, FDPS, TNFSF11, ESR1, MMP9, and BRCA2 in breast cancer tissues, while survival analysis linked elevated FDPS, MMP9, and BRCA2 expression to poor prognosis. Network analyses highlighted pathways related to mevalonate metabolism, hormone signaling, angiogenesis, extracellular matrix remodeling, and the RANK\/RANKL\/OPG axis. These findings support the potential repurposing of bisphosphonates, particularly zoledronate, for breast cancer-associated bone disease.<\/jats:p>","DOI":"10.3390\/biology15120952","type":"journal-article","created":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T10:25:34Z","timestamp":1781778334000},"page":"952","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Effects of Bisphosphonates Used in Osteoporosis Treatment on Breast Cancer: Analysis with Integrative Bioinformatics Methods, DFT, ADMET and Molecular Docking Analysis"],"prefix":"10.3390","volume":"15","author":[{"given":"Sevil Ceyhan","family":"Dogan","sequence":"first","affiliation":[{"name":"Department of Physical Medicine and Rehabilitation, Faculty of Medicine, Sivas Cumhuriyet University, Sivas 58140, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5068-1762","authenticated-orcid":false,"given":"Kenan","family":"Goren","sequence":"additional","affiliation":[{"name":"Department of Organic Chemistry, Faculty of Arts and Sciences, Kafkas University, Kars 36100, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Shapiro, C.L. 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