{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T14:39:26Z","timestamp":1788964766468,"version":"build-2803163510"},"reference-count":51,"publisher":"Public Library of Science (PLoS)","issue":"12","license":[{"start":{"date-parts":[[2025,12,4]],"date-time":"2025-12-04T00:00:00Z","timestamp":1764806400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100017695","name":"Health Commission of Hunan Province","doi-asserted-by":"publisher","award":["B202303068776"],"award-info":[{"award-number":["B202303068776"]}],"id":[{"id":"10.13039\/100017695","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004735","name":"Natural Science Foundation of Hunan Province","doi-asserted-by":"publisher","award":["2024JJ7533"],"award-info":[{"award-number":["2024JJ7533"]}],"id":[{"id":"10.13039\/501100004735","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004735","name":"Natural Science Foundation of Hunan Province","doi-asserted-by":"publisher","award":["2023JJ50411"],"award-info":[{"award-number":["2023JJ50411"]}],"id":[{"id":"10.13039\/501100004735","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100014978","name":"Hunan University of Chinese Medicine","doi-asserted-by":"publisher","award":["2024XJZC003"],"award-info":[{"award-number":["2024XJZC003"]}],"id":[{"id":"10.13039\/501100014978","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>This study aimed to investigate the optimal age for developing a model of postmenopausal osteoporosis via bilateral oophorectomy. Moreover, the timing and effectiveness of the established model was monitored to provide scientific foundation to guide future research aimed investigating the timing and model selection in various interventions and treatments.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Data from animal experiments investigating postmenopausal osteoporosis published in the past 10 years were retrieved from the Web of Science Core Collection database. The obtained data were imported into Excel, CiteSpace, and VOSviewer software and screened to identify high-frequency animal models. The sexual maturation status of these high-frequency animals at different ages was examined through vaginal smear HE staining, measurement of serum estrogen (E2) levels, and examination of ovarian uterine morphology. Bilateral ovariectomy was performed in sexually mature animals, and the HE staining assay was carried out on vaginal smears for five consecutive days starting from the fourth day post-operation to confirm the success of the ovariectomy. Subsequently, alterations in bone mineral density and bone histopathology were dynamically analyzed at 6-, 9-, and 12-weeks post-operation, which enabled us to systematically evaluate the model\u2019s effectiveness.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Result<\/jats:title>\n                    <jats:p>The search identified 668 articles and bibliometric analyses demonstrated that the C57BL\/6j mice were the most frequently used species, accounting for 44.3%, with the 8-week-old C57BL\/6j mice being the most common (n\u2009=\u2009139, 34.75%). Mice at different weeks of age were selected as the subjects of sexual maturation test. It was observed that there were no marked changes in estrous cycle in the vaginal smear of 4w and 6w groups, but notable cellular changes and estrous cycle fluctuations were observed in the vaginal smear of 8w, 10w and 12w. The serum level of E2 was not significantly different between the 4w and 6w groups, but the level of E2 in the 8w, 10w and 12w groups was significantly higher relative to that of the proestrus and diestrus (P\u2009&lt;\u20090.05). Moreover, the ovaries of the 4w and 6w groups were smaller and flat, most of them were primordial follicles and primary follicles, without discernable a corpus luteum. The ovaries of the 8, 10 and 12w groups were enlarged and full, with mature follicles and corpus luteum detected in the 8w and 12w groups. In the time monitoring experiment, the results vaginal smear of the sham operation group revealed a complete estrus cycle, but it was irregular in the model group. Mice in the sham operation group exhibited full uterine shape, thick uterine body, which appeared fleshy pink. In addition, the uterine shape of the models in all groups following bilateral ovariectomy exhibited atrophic, irregular, thin, and gray. The trabecular bone in the model groups was disorderly, broken, and decreased compared to those of the sham operation group. At 9 and 12 weeks, the trabecular bone fracture disorder was severe in the model group; however, the number of trabecular bones was not significantly different between the 9-week model group and the 12-week model group. Furthermore, bone mineral density (BMD), bone volume fraction (BV\/TV), and trabecular bone number (Tb.N) were comparable between the 6-week model group and the sham operation group. In contrast, the BMD, BV\/TV, and Tb.N in the 12-week model group exhibited a modest but non-significant decrease relative to the 9-week model group. The concentration level of BALP and TRACP-5b did not differ significantly between the 6-week model group and the sham operation group. In contrast, BALP was significantly lower in the 9-week and 12-week model groups compared to levels in the sham operation group, while the levels of TRACP-5b in the 9-week and 12-week model groups were significantly higher than those in the sham operation group(P\u2009&lt;\u20090.001).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This study demonstrates that, at 8 weeks of age, C57BL\/6J mice are the most suitable animal model for bilateral ovariectomy, owing to their stable maturity. A postmenopausal osteoporosis model can be established 9 weeks after the initial operation, which can facilitate further research on postmenopausal osteoporosis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0336703","type":"journal-article","created":{"date-parts":[[2025,12,4]],"date-time":"2025-12-04T18:36:40Z","timestamp":1764873400000},"page":"e0336703","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":4,"title":["Determination of appropriate time for establishing a model of postmenopausal osteoporosis induced by bilateral oophorectomy: From bibliometric analysis to animal experiment"],"prefix":"10.1371","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-4856-7881","authenticated-orcid":true,"given":"Yan","family":"She","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linyu","family":"Yin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yijin","family":"Kuang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yujing","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dandan","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xian","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shanxi","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Songtao","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kun","family":"Ai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,12,4]]},"reference":[{"issue":"1","key":"pone.0336703.ref001","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1007\/s00198-018-4704-5","article-title":"European guidance for the diagnosis and management of osteoporosis in postmenopausal women","volume":"30","author":"Scientific Advisory Board of the European Society for Clinical and Economic Aspects of Osteoporosis (ESCEO) and the Committees of Scientific Advisors and National Societies of the International Osteoporosis Foundation (IOF)","year":"2019","journal-title":"Osteoporos Int"},{"issue":"1","key":"pone.0336703.ref002","doi-asserted-by":"crossref","first-page":"568","DOI":"10.1186\/s13018-024-05068-1","article-title":"Mortality associated with osteoporosis and pathological fractures in the United States (1999-2020): a multiple-cause-of-death study","volume":"19","author":"R Huo","year":"2024","journal-title":"J Orthop Surg Res"},{"key":"pone.0336703.ref003","doi-asserted-by":"crossref","first-page":"1","DOI":"10.4158\/GL-2020-0524SUPPL","article-title":"American association of clinical endocrinologists\/American college of endocrinology clinical practice guidelines for the diagnosis and treatment of postmenopausal osteoporosis-2020 update","volume":"26","author":"PM Camacho","year":"2020","journal-title":"Endocr Pract"},{"issue":"1","key":"pone.0336703.ref004","doi-asserted-by":"crossref","first-page":"2181356","DOI":"10.1080\/10641963.2023.2181356","article-title":"Factors influencing blood pressure variability in postmenopausal women: evidence from the China health and nutrition survey","volume":"45","author":"Z Tao","year":"2023","journal-title":"Clin Exp Hypertens"},{"issue":"1","key":"pone.0336703.ref005","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1186\/s42826-022-00128-1","article-title":"Role of animal models in biomedical research: a review","volume":"38","author":"P Mukherjee","year":"2022","journal-title":"Lab Anim Res"},{"issue":"12","key":"pone.0336703.ref006","doi-asserted-by":"crossref","first-page":"1731","DOI":"10.1038\/s43587-024-00767-0","article-title":"Exploring the effects of estrogen deficiency and aging on organismal homeostasis during menopause","volume":"4","author":"C Camon","year":"2024","journal-title":"Nat Aging"},{"key":"pone.0336703.ref007","unstructured":"Zakaria R, Rahbi BA, Ahmad AH, Said Rozzana M, Othman Z, Azman KF, et al. 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