{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T04:07:57Z","timestamp":1785211677478,"version":"3.55.0"},"reference-count":24,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T00:00:00Z","timestamp":1761696000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T00:00:00Z","timestamp":1761696000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"name":"Foundation for Research Support of the State of S\u00e3o Paulo (FAPESP), Brazil."}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"DOI":"10.1038\/s41598-024-80471-6","type":"journal-article","created":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T15:06:05Z","timestamp":1761750365000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["The selective serotonin reuptake inhibitor escitalopram oxalate negatively impacts the fracture healing in healthy adults and in osteoporotic rats"],"prefix":"10.1038","volume":"15","author":[{"given":"Roberta","family":"Carminati Shimano","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ariane","family":"Zamarioli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Paula","family":"Macedo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Viviane","family":"de Cassia Oliveira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felipe","family":"Manuel Chiocca Nascimento","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patr\u00edcia","family":"Madalena San Greg\u00f3rio Guedes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricardo","family":"Tadeu Lopes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 Batista","family":"Volpon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,10,29]]},"reference":[{"key":"80471_CR1","doi-asserted-by":"publisher","first-page":"821","DOI":"10.1002\/jbmr.3045","volume":"32","author":"V Bradaschia-Correa","year":"2017","unstructured":"Bradaschia-Correa, V. et al. The selective serotonin reuptake inhibitor fluoxetine directly inhibits osteoblast differentiation and mineralization during fracture healing in mice. J. Bone Miner. Res. 32, 821\u2013833 (2017).","journal-title":"J. Bone Miner. Res."},{"key":"80471_CR2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-92821-9","author":"S Kang","year":"2021","unstructured":"Kang, S. et al. Use of serotonin reuptake inhibitors and risk of subsequent bone loss in a nationwide population-based cohort study. Sci. Rep. https:\/\/doi.org\/10.1038\/s41598-021-92821-9 (2021).","journal-title":"Sci. Rep."},{"key":"80471_CR3","doi-asserted-by":"publisher","first-page":"3477","DOI":"10.2147\/DDDT.S216822","volume":"13","author":"KS Agacayak","year":"2019","unstructured":"Agacayak, K. S., Guler, R. & Ilyasov, B. Evaluation of the effect of long-term use of antidepressants in the SSRI group on bone density with dental volumetric tomography. Drug Des. Dev. Ther. 13, 3477\u20133484 (2019).","journal-title":"Drug Des. Dev. Ther."},{"key":"80471_CR4","first-page":"7","volume":"35","author":"T Richter","year":"2014","unstructured":"Richter, T., Paluch, Z. & Alusik, S. The non-antidepressant effects of citalopram: A clinician\u2019s perspective. Neuroendocrinol. Lett. 35, 7\u201312 (2014).","journal-title":"Neuroendocrinol. Lett."},{"key":"80471_CR5","doi-asserted-by":"publisher","first-page":"117827","DOI":"10.1016\/j.lfs.2020.117827","volume":"255","author":"E Durham","year":"2020","unstructured":"Durham, E., Zhang, Y., LaRue, A., Bradshaw, A. & Cray, J. Selective serotonin reuptake inhibitors (SSRI) affect murine bone lineage cells. Life Sci. 255, 117827 (2020).","journal-title":"Life Sci."},{"key":"80471_CR6","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1016\/j.bone.2009.07.083","volume":"46","author":"EM Haney","year":"2010","unstructured":"Haney, E. M., Warden, S. J. & Bliziotes, M. M. Effects of selective serotonin reuptake inhibitors on bone health in adults: Time for recommendations about screening, prevention and management?. Bone 46, 13\u201317 (2010).","journal-title":"Bone"},{"key":"80471_CR7","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1111\/sms.12650","volume":"27","author":"AP Macedo","year":"2017","unstructured":"Macedo, A. P. et al. Influence of treadmill training on bone structure under osteometabolic alteration in rats subjected to high-fat diet. Scand. J. Med. Sci. Sport. 27, 167\u2013176 (2017).","journal-title":"Scand. J. Med. Sci. Sport."},{"key":"80471_CR8","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1016\/j.bone.2016.05.003","volume":"89","author":"PH Rauma","year":"2016","unstructured":"Rauma, P. H. et al. Effects of antidepressants on postmenopausal bone loss - A 5-year longitudinal study from the OSTPRE cohort. Bone 89, 25\u201331 (2016).","journal-title":"Bone"},{"key":"80471_CR9","doi-asserted-by":"publisher","DOI":"10.3390\/ijerph15071373","author":"JU Schweiger","year":"2018","unstructured":"Schweiger, J. U. et al. The use of antidepressive agents and bone mineral density in women: A meta-analysis. Int. J. Environ. Res. Public Health https:\/\/doi.org\/10.3390\/ijerph15071373 (2018).","journal-title":"Int. J. Environ. Res. Public Health"},{"key":"80471_CR10","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1016\/j.ejphar.2018.02.026","volume":"825","author":"M Kumar","year":"2018","unstructured":"Kumar, M., Wadhwa, R., Kothari, P., Trivedi, R. & Vohora, D. Differential effects of serotonin reuptake inhibitors fluoxetine and escitalopram on bone markers and microarchitecture in Wistar rats. Eur. J. Pharmacol. 825, 57\u201362 (2018).","journal-title":"Eur. J. Pharmacol."},{"key":"80471_CR11","doi-asserted-by":"publisher","DOI":"10.1038\/s41398-022-02083-w","author":"RW Lam","year":"2022","unstructured":"Lam, R. W. et al. Fluoxetine improves bone microarchitecture and mechanical properties in rodents undergoing chronic mild stress \u2013 an animal model of depression. Transl. Psychiatry https:\/\/doi.org\/10.1038\/s41398-022-02083-w (2022).","journal-title":"Transl. Psychiatry"},{"key":"80471_CR12","doi-asserted-by":"publisher","first-page":"1170","DOI":"10.1038\/nm.4166","volume":"22","author":"MJ Ortu\u00f1o","year":"2016","unstructured":"Ortu\u00f1o, M. J. et al. Serotonin-reuptake inhibitors act centrally to cause bone loss in mice by counteracting a local anti-resorptive effect. Nat. Med. 22, 1170\u20131179 (2016).","journal-title":"Nat. Med."},{"key":"80471_CR13","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1016\/j.afos.2017.05.002","volume":"3","author":"R Wadhwa","year":"2017","unstructured":"Wadhwa, R., Kumar, M., Talegaonkar, S. & Vohora, D. Serotonin reuptake inhibitors and bone health: A review of clinical studies and plausible mechanisms. Osteoporos. Sarcopenia 3, 75\u201381 (2017).","journal-title":"Osteoporos. Sarcopenia"},{"key":"80471_CR14","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1083\/jcb.201006123","volume":"191","author":"P Ducy","year":"2010","unstructured":"Ducy, P. & Karsenty, G. The two faces of serotonin in bone biology. J. Cell Biol. 191, 7\u201313. https:\/\/doi.org\/10.1083\/jcb.201006123 (2010).","journal-title":"J. Cell Biol."},{"key":"80471_CR15","doi-asserted-by":"publisher","DOI":"10.3390\/healthcare10050803","author":"R de Filippis","year":"2022","unstructured":"de Filippis, R. et al. Antidepressants and vertebral and hip risk fracture: An updated systematic review and meta-analysis. Healthcare (Switzerland) https:\/\/doi.org\/10.3390\/healthcare10050803 (2022).","journal-title":"Healthcare (Switzerland)"},{"key":"80471_CR16","doi-asserted-by":"publisher","DOI":"10.1038\/s41368-018-0026-x","author":"RN Howie","year":"2018","unstructured":"Howie, R. N. et al. Selective serotonin reuptake inhibitor sertraline inhibits bone healing in a calvarial defect model. Int. J. Oral Sci. https:\/\/doi.org\/10.1038\/s41368-018-0026-x (2018).","journal-title":"Int. J. Oral Sci."},{"key":"80471_CR17","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1136\/ejhpharm-2019-001893","volume":"28","author":"MQ Gorgas","year":"2021","unstructured":"Gorgas, M. Q. et al. Effects of selective serotonin reuptake inhibitors and other antidepressant drugs on the risk of hip fracture: A case-control study in an elderly Mediterranean population. Eur. J. Hosp. Pharm. 28, 28\u201332 (2021).","journal-title":"Eur. J. Hosp. Pharm."},{"key":"80471_CR18","first-page":"624","volume":"4","author":"P Sengupta","year":"2013","unstructured":"Sengupta, P. The laboratory rat: Relating its age with human\u2019s. Int. J. Prev. Med. 4, 624\u2013630 (2013).","journal-title":"Int. J. Prev. Med."},{"key":"80471_CR19","doi-asserted-by":"publisher","first-page":"1523","DOI":"10.1111\/sms.13058","volume":"28","author":"RC Shimano","year":"2018","unstructured":"Shimano, R. C. et al. Effects of high-impact exercise on the physical properties of bones of ovariectomized rats fed to a high-protein diet. Scand. J. Med. Sci. Sport. 28, 1523\u20131531 (2018).","journal-title":"Scand. J. Med. Sci. Sport."},{"key":"80471_CR20","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41598-019-51702-y","volume":"9","author":"FAT de Figueiredo","year":"2019","unstructured":"de Figueiredo, F. A. T. et al. Doxycycline reduces osteopenia in female rats. Sci. Rep. 9, 1\u201314 (2019).","journal-title":"Sci. Rep."},{"key":"80471_CR21","doi-asserted-by":"publisher","first-page":"E1732","DOI":"10.1210\/jc.2014-2288","volume":"99","author":"SJ Diem","year":"2014","unstructured":"Diem, S. J. et al. Effects of escitalopram on markers of bone turnover: A randomized clinical trial. J. Clin. Endocrinol. Metab. 99, E1732\u2013E1737 (2014).","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"80471_CR22","doi-asserted-by":"publisher","first-page":"365","DOI":"10.1038\/s41393-019-0377-y","volume":"58","author":"MM Butezloff","year":"2020","unstructured":"Butezloff, M. M. et al. Gene expression changes are associated with severe bone loss and deficient fracture callus formation in rats with complete spinal cord injury. Spinal Cord 58, 365\u2013376 (2020).","journal-title":"Spinal Cord"},{"key":"80471_CR23","doi-asserted-by":"publisher","first-page":"1468","DOI":"10.1002\/jbmr.141","volume":"25","author":"ML Bouxsein","year":"2010","unstructured":"Bouxsein, M. L. et al. Guidelines for assessment of bone microstructure in rodents using micro-computed tomography. J. Bone Miner. Res. 25, 1468\u20131486. https:\/\/doi.org\/10.1002\/jbmr.141 (2010).","journal-title":"J. Bone Miner. Res."},{"key":"80471_CR24","first-page":"1","volume":"4","author":"AM Parfitt","year":"1988","unstructured":"Parfitt, A. M. Bone histomorphometry: Standardization of nomenclature, symbols and units. Summary of proposed system. Bone Miner. 4, 1\u20135 (1988).","journal-title":"Bone Miner."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-80471-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-80471-6","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-80471-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T15:06:07Z","timestamp":1761750367000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-80471-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,29]]},"references-count":24,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["80471"],"URL":"https:\/\/doi.org\/10.1038\/s41598-024-80471-6","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,29]]},"assertion":[{"value":"20 October 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 November 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 October 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"37755"}}