{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T03:12:30Z","timestamp":1768273950674,"version":"3.49.0"},"reference-count":28,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2025,6,27]],"date-time":"2025-06-27T00:00:00Z","timestamp":1750982400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento e Pessoal de N\u00edvel Superior-Brasil (CAPES)","award":["001"],"award-info":[{"award-number":["001"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Bioengineering"],"abstract":"<jats:p>Background: Osteoporosis is a systemic disease characterized by a progressive decrease in bone density and deterioration of the tissue\u2019s microarchitecture. This results in greater structural fragility and a higher risk of fractures. Osteopenia represents the beginning of the process of decreasing bone density and, if left untreated, can lead to osteoporosis. The objective of this study was to validate an experimental model for establishing cases of decreased bone density that allows for the creation of different levels of severity of mineral loss and changes in bone microstructure. Materials and Methods: Twenty female Wistar rats, 12 weeks old and with a body weight ranging from 300 to 400 g, were used in this study. The animals were randomly distributed into five groups (n = 5 per group): a control group (CG), where the animals were not ovariectomized (OVX), and four experimental groups, where the animals were OVX and euthanized at different times: 30 days (G30), 40 days (G40), 60 days (G60), and 80 days (G80). The animals in the experimental groups underwent bilateral ovariectomy to induce mineral loss. The femurs were collected after the periods established for each group and analyzed using microcomputed tomography (\u03bcCT) to determine bone density and count the number of trabeculae. Furthermore, the T-score was calculated for each group. Results: There were significant differences in bone density when comparing all groups, with GC &gt; G30 &gt; G40 &gt; G60 &gt; G80. For the number of trabeculae, GC presented more trabeculae than all other groups. More trabeculae were also observed in G30 when compared to G40, G60, and G80; however, there were no differences between G40, G60, and G80. Regarding the calculation of the T-score by group, osteopenia was observed in G30 (T-score: \u22122.42) and osteoporosis was observed in G40, G60, and G80 (T-scores: \u22124.38, \u22126.34, and \u22127.71, respectively). Conclusions: The results demonstrate that ovariectomy induces progressive changes in bone structure, with the onset of osteopenia 30 days after ovariectomy and osteoporosis after 40 days in this experimental model. These results may aid future investigations that seek to focus on the specific treatment of osteopenia and\/or osteoporosis.<\/jats:p>","DOI":"10.3390\/bioengineering12070702","type":"journal-article","created":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T07:42:06Z","timestamp":1751355726000},"page":"702","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["The Validation of an Experimental Model in Wistar Female Rats to Study Osteopenia and Osteoporosis"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3894-0359","authenticated-orcid":false,"given":"Artur Lage","family":"Pedroso","sequence":"first","affiliation":[{"name":"Division of Implant Dentistry, Faculdade S\u00e3o Leopoldo Mandic, Campinas 13045-755, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raul","family":"Canal","sequence":"additional","affiliation":[{"name":"Sociedade Brasileira de Direito M\u00e9dico e Bio\u00e9tica, Bras\u00edlia 70322-901, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5863-9101","authenticated-orcid":false,"given":"Sergio Alexandre","family":"Gehrke","sequence":"additional","affiliation":[{"name":"Department of Implantology, Bioface\/Postgrados en Odontolog\u00eda\/Universidad Catolica de Murcia, Montevideo 11100, Uruguay"},{"name":"Department of Biotechnology, Universidad Cat\u00f3lica de Murcia, 30107 Murcia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8733-3083","authenticated-orcid":false,"given":"Eleani Maria","family":"da Costa","sequence":"additional","affiliation":[{"name":"Department of Materials Engineering, Pontificial Catholic University of Rio Grande do Sul, Porto Alegre 90619-900, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1374-6146","authenticated-orcid":false,"given":"Antonio","family":"Scarano","sequence":"additional","affiliation":[{"name":"Department of Innovative Technologies in Medicine & Dentistry, University of Chieti-Pescara, 66013 Chieti, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fernanda Barchesi","family":"Zanelatto","sequence":"additional","affiliation":[{"name":"Division of Implant Dentistry, Faculdade S\u00e3o Leopoldo Mandic, Campinas 13045-755, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7935-1062","authenticated-orcid":false,"given":"Andr\u00e9 Antonio","family":"Pelegrine","sequence":"additional","affiliation":[{"name":"Division of Implant Dentistry, Faculdade S\u00e3o Leopoldo Mandic, Campinas 13045-755, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2359","DOI":"10.1007\/s00198-014-2794-2","article-title":"National Osteoporosis Foundation. Clinician\u2019s Guide to Prevention and Treatment of Osteoporosis","volume":"25","author":"Cosman","year":"2014","journal-title":"Osteoporos. Int."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1007\/s00198-008-0560-z","article-title":"European guidance for the diagnosis and management of osteoporosis in postmenopausal women","volume":"19","author":"Kanis","year":"2008","journal-title":"Osteoporos. Int."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1007\/s00198-002-1301-3","article-title":"A comprehensive review of treatments for postmenopausal osteoporosis","volume":"14","author":"Hauselmann","year":"2003","journal-title":"Osteoporos. Int."},{"key":"ref_4","first-page":"2155","article-title":"Osteoporosis and fracture risk: The role of bone turnover","volume":"30","author":"Compston","year":"2019","journal-title":"Osteoporos. Int."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1276","DOI":"10.1016\/S0140-6736(10)62349-5","article-title":"Osteoporosis: Now and the future","volume":"7","author":"Rachner","year":"2011","journal-title":"Lancet"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1347","DOI":"10.1007\/s00198-008-0801-1","article-title":"Spine radiographs to improve the identification of women at high risk for fractures","volume":"20","author":"Netelenbos","year":"2009","journal-title":"Osteoporos. Int."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1007\/s11154-010-9154-0","article-title":"Diagnosis and treatment of osteopenia","volume":"11","author":"Karaguzel","year":"2010","journal-title":"Rev. Endocr. Metab. Disord."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1726","DOI":"10.1007\/s00198-006-0172-4","article-title":"An estimate of the worldwide prevalence and disability associated with osteoporotic fractures","volume":"17","author":"Johnell","year":"2006","journal-title":"Osteoporos. Int."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"604","DOI":"10.15537\/smj.2017.6.19793","article-title":"Long-term use of bisphosphonates in osteoporosis","volume":"6","author":"Alwahhabi","year":"2017","journal-title":"Saudi Med. J."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2189","DOI":"10.1001\/jama.281.23.2189","article-title":"The effect of raloxifene on risk of breast cancer in postmenopausal women: Results from the MORE randomized trial. Multiple Outcomes of Raloxifene Evaluation","volume":"282","author":"Cummings","year":"1999","journal-title":"JAMA"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1517\/17425255.2015.1000860","article-title":"Denosumab for the treatment of osteoporosis","volume":"3","author":"Zaheer","year":"2015","journal-title":"Expert. Opin. Drug Metab. Toxicol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1281","DOI":"10.1007\/s00198-015-3440-3","article-title":"The National Osteoporosis Foundation\u2019s position statement on peak bone mass development and lifestyle factors: A systematic review and implementation recommendations","volume":"27","author":"Weaver","year":"2016","journal-title":"Osteoporos. Int."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1177\/1099800402239628","article-title":"Effects of Exercise on bone density, Balance, and Self-Efficacy in Older Women","volume":"4","author":"Jessup","year":"2003","journal-title":"Biol. Res. Nurs."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1016\/0169-6009(92)90809-R","article-title":"On the rat model of human osteopenias and osteoporoses","volume":"18","author":"Frost","year":"1992","journal-title":"Bone Miner."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1007\/s00198-016-3771-8","article-title":"Do osteoporotic fractures constitute a greater recalcitrant challenge for skeletal regeneration? Investigating the efficacy of BMP-7 and zoledronate treatment of diaphyseal fractures in an open fracture osteoporotic rat model","volume":"28","author":"Mathavan","year":"2017","journal-title":"Osteoporos. Int."},{"key":"ref_16","first-page":"176","article-title":"The importance of animal models in osteoporosis research","volume":"8","author":"Baird","year":"2018","journal-title":"Bone Rep."},{"key":"ref_17","first-page":"10626","article-title":"Development of an osteoporotic animal model","volume":"15","author":"Cheung","year":"2014","journal-title":"Int. J. Mol. Sci."},{"key":"ref_18","first-page":"1","article-title":"Osteoporosis models for evaluation of treatment regimens","volume":"4","author":"Cheung","year":"2014","journal-title":"J. Orthop. Translat."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"630","DOI":"10.1016\/j.jpain.2008.02.006","article-title":"The influence of sex and ovarian hormones on temporomandibular joint nociception in rats","volume":"9","author":"Fischer","year":"2008","journal-title":"J. Pain."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"586","DOI":"10.1590\/S0004-27302006000400004","article-title":"Bone density testing in clinical practice","volume":"50","author":"Lewiecki","year":"2006","journal-title":"Arq. Bras. Endocrinol. Metabol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2520","DOI":"10.1002\/jbmr.2269","article-title":"The recent prevalence of osteoporosis and low bone mass in the United States based on bone mineral density at the femoral neck or lumbar spine","volume":"29","author":"Wright","year":"2014","journal-title":"J. Bone Miner. Res."},{"key":"ref_22","unstructured":"U.S Department of Health and Human Services\u2014Food and Drug Administration (2025, April 03). Osteoporosis: Nonclinical Evaluation of Drugs Intended for Treatment\u2014Guidance for Industry., Available online: http:\/\/www.fda.gov\/."},{"key":"ref_23","first-page":"89","article-title":"Ovariectomized rat model of osteoporosis: A practical guide","volume":"19","author":"Yousefzadeh","year":"2020","journal-title":"EXCLI J."},{"key":"ref_24","first-page":"1491","article-title":"Are there differences between Sprague-Dawley and Wistar rats in long-term effects of ovariectomy as a model for postmenopausal osteoporosis?","volume":"8","author":"Fang","year":"2015","journal-title":"Int. J. Clin. Exp. Pathol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1180","DOI":"10.1016\/j.bone.2004.07.010","article-title":"Low-level lifetime exposure to cadmium decreases skeletal mineralization and enhances bone loss in aged rats","volume":"35","year":"2004","journal-title":"Bone"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1468","DOI":"10.1002\/jbmr.141","article-title":"Guidelines for assessment of bone microstructure in rodents using micro-computed tomography","volume":"25","author":"Bouxsein","year":"2010","journal-title":"J. Bone Miner. Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1038\/s41413-022-00190-4","article-title":"Mechanical regulation of bone remodeling","volume":"10","author":"Wang","year":"2022","journal-title":"Bone Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1007\/s00223-021-00936-y","article-title":"Silibinin Can Promote Bone Regeneration of Selenium Hydrogel by Reducing the Oxidative Stress Pathway in Ovariectomized Rats","volume":"110","author":"Tao","year":"2022","journal-title":"Calcif. Tissue Int."}],"container-title":["Bioengineering"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2306-5354\/12\/7\/702\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:00:19Z","timestamp":1760032819000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2306-5354\/12\/7\/702"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,27]]},"references-count":28,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2025,7]]}},"alternative-id":["bioengineering12070702"],"URL":"https:\/\/doi.org\/10.3390\/bioengineering12070702","relation":{},"ISSN":["2306-5354"],"issn-type":[{"value":"2306-5354","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,27]]}}}