{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T03:05:15Z","timestamp":1773025515749,"version":"3.50.1"},"reference-count":51,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,11,10]],"date-time":"2025-11-10T00:00:00Z","timestamp":1762732800000},"content-version":"vor","delay-in-days":313,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T00:00:00Z","timestamp":1735689600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100002947","name":"Anhui Medical University","doi-asserted-by":"publisher","award":["2022xkj006"],"award-info":[{"award-number":["2022xkj006"]}],"id":[{"id":"10.13039\/501100002947","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003995","name":"Natural Science Foundation of Anhui Province","doi-asserted-by":"publisher","award":["2308085QH288"],"award-info":[{"award-number":["2308085QH288"]}],"id":[{"id":"10.13039\/501100003995","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003995","name":"Natural Science Foundation of Anhui Province","doi-asserted-by":"publisher","award":["2108085Y26"],"award-info":[{"award-number":["2108085Y26"]}],"id":[{"id":"10.13039\/501100003995","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82273710"],"award-info":[{"award-number":["82273710"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82404354"],"award-info":[{"award-number":["82404354"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["International Journal of Genomics"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:sec>\n                    <jats:title>Backgrounds<\/jats:title>\n                    <jats:p>Observational studies have suggested possible links between reproductive factors and bone mineral density (BMD) and osteoporosis (OP), but the causal impact of menstrual factors on BMD remains obscure.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>This study is aimed at inferring causal associations between key menstrual factors and site\u2010\/age\u2010specific BMD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Genetic variants associated with age at menarche (AAM), last menstrual period (LMP), and length of menstrual cycle (LMC) were obtained from genome\u2010wide association studies (GWASs). The site\u2010\/age\u2010specific BMD genetic data were derived from the Genetic Factors for OP Consortium (GEFOS). Causal associations were evaluated using a two\u2010sample Mendelian randomization (MR) approach and a multivariable MR (MVMR) model.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      LMP was causally associated with increased estimated heel BMD (eBMD) (beta = 0.055; 95% CI: 0.020, 0.089;\n                      <jats:italic>P<\/jats:italic>\n                      <jats:sub>FDR<\/jats:sub>\n                      = 0.001) and lumbar spine BMD (LS\u2010BMD) (beta = 0.103; 95% CI: 0.031, 0.175;\n                      <jats:italic>P<\/jats:italic>\n                      <jats:sub>FDR<\/jats:sub>\n                      = 0.039). LMC was inversely associated with TB\u2010BMD in both discovery (beta = \u22120.207; 95% CI: \u22120.323, \u22120.091;\n                      <jats:italic>P<\/jats:italic>\n                      <jats:sub>FDR<\/jats:sub>\n                      = 0.001) and replication cohorts (beta = \u22120.211; 95% CI: \u22120.335, \u22120.087;\n                      <jats:italic>P<\/jats:italic>\n                      <jats:sub>FDR<\/jats:sub>\n                      = 0.002). LMP was negatively associated with TB\u2010BMD among individuals aged 15\u201330 but was positively associated in those aged 45\u201360. Additional MVMR analysis supported direct causal relationships of LMP and LMC with site\u2010specific BMD (eBMD and TB\u2010BMD) and age\u2010specific BMD (age 45\u201360).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our study observes the causal effects of LMP and LMC on BMD, with variations across anatomical sites and age groups. These findings enhance our understanding of the relationship between menstrual factors and bone health, providing evidence to inform targeted prevention strategies for OP.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1155\/ijog\/9979878","type":"journal-article","created":{"date-parts":[[2025,11,10]],"date-time":"2025-11-10T12:06:28Z","timestamp":1762776388000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Genetic Insights Into the Relationship Between Menstrual Factors and Site\u2010\/Age\u2010Specific Bone Mineral Density"],"prefix":"10.1155","volume":"2025","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-6379-6084","authenticated-orcid":false,"given":"Sheng","family":"Li","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-5246-010X","authenticated-orcid":false,"given":"Yan-Yu","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-8101-4812","authenticated-orcid":false,"given":"Xiao","family":"Hu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-4867-6782","authenticated-orcid":false,"given":"Qian-Qian","family":"Shi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-1685-0846","authenticated-orcid":false,"given":"Jia-Jun","family":"Deng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-3179-6921","authenticated-orcid":false,"given":"Hai-Fen","family":"Wei","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-4131-5295","authenticated-orcid":false,"given":"Chun-Rong","family":"Ma","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8218-5747","authenticated-orcid":false,"given":"Hai-Feng","family":"Pan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8838-682X","authenticated-orcid":false,"given":"Peng","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,11,10]]},"reference":[{"key":"e_1_2_12_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcna.2021.05.016"},{"key":"e_1_2_12_2_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13018-021-02772-0"},{"key":"e_1_2_12_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcna.2020.06.004"},{"key":"e_1_2_12_4_2","doi-asserted-by":"publisher","DOI":"10.7326\/M22-0684"},{"key":"e_1_2_12_5_2","doi-asserted-by":"publisher","DOI":"10.1177\/1759720X11430858"},{"key":"e_1_2_12_6_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.2009.04954.x"},{"key":"e_1_2_12_7_2","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2012.00019"},{"key":"e_1_2_12_8_2","doi-asserted-by":"publisher","DOI":"10.1177\/00333549141291S206"},{"key":"e_1_2_12_9_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11657-021-00959-w"},{"key":"e_1_2_12_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.abb.2010.07.006"},{"key":"e_1_2_12_11_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00198-002-1364-1"},{"key":"e_1_2_12_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0278-6915(99)00145-3"},{"key":"e_1_2_12_13_2","doi-asserted-by":"publisher","DOI":"10.1359\/jbmr.1998.13.7.1191"},{"key":"e_1_2_12_14_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199011013231801"},{"key":"e_1_2_12_15_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.k601"},{"key":"e_1_2_12_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41576-018-0020-3"},{"key":"e_1_2_12_17_2","doi-asserted-by":"publisher","DOI":"10.1093\/aje\/kwu283"},{"key":"e_1_2_12_18_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehad736"},{"key":"e_1_2_12_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-022-01062-7"},{"key":"e_1_2_12_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-04103-z"},{"key":"e_1_2_12_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature13545"},{"key":"e_1_2_12_22_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddy317"},{"key":"e_1_2_12_23_2","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyr036"},{"key":"e_1_2_12_24_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1077088"},{"key":"e_1_2_12_25_2","doi-asserted-by":"publisher","DOI":"10.1002\/gepi.21758"},{"key":"e_1_2_12_26_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0222362"},{"key":"e_1_2_12_27_2","doi-asserted-by":"publisher","DOI":"10.1002\/sim.6522"},{"key":"e_1_2_12_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.numecd.2021.02.027"},{"key":"e_1_2_12_29_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-024-59159-4"},{"key":"e_1_2_12_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2023.122280"},{"key":"e_1_2_12_31_2","doi-asserted-by":"publisher","DOI":"10.1155\/2018\/1206235"},{"key":"e_1_2_12_32_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.analchem.2c03719"},{"key":"e_1_2_12_33_2","doi-asserted-by":"publisher","DOI":"10.1093\/aje\/kwg066"},{"key":"e_1_2_12_34_2","doi-asserted-by":"publisher","DOI":"10.1097\/GME.0000000000001831"},{"key":"e_1_2_12_35_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41413-020-0102-7"},{"key":"e_1_2_12_36_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-022-15241-3"},{"key":"e_1_2_12_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ogc.2018.07.004"},{"key":"e_1_2_12_38_2","doi-asserted-by":"publisher","DOI":"10.1186\/s11556-021-00262-0"},{"key":"e_1_2_12_39_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-024-73427-3"},{"key":"e_1_2_12_40_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-32647-0"},{"key":"e_1_2_12_41_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-93152-5"},{"key":"e_1_2_12_42_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2013-2954"},{"key":"e_1_2_12_43_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-0528.2012.03324.x"},{"key":"e_1_2_12_44_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12916-024-03361-8"},{"key":"e_1_2_12_45_2","doi-asserted-by":"publisher","DOI":"10.1002\/ijgo.14820"},{"key":"e_1_2_12_46_2","doi-asserted-by":"publisher","DOI":"10.1093\/ntr\/ntp179"},{"key":"e_1_2_12_47_2","doi-asserted-by":"publisher","DOI":"10.1007\/s40618-014-0175-5"},{"key":"e_1_2_12_48_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.315.7112.841"},{"key":"e_1_2_12_49_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms222413662"},{"key":"e_1_2_12_50_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-023-50423-7"},{"key":"e_1_2_12_51_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12889-024-20628-0"}],"container-title":["International Journal of Genomics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1155\/ijog\/9979878","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1155\/ijog\/9979878","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1155\/ijog\/9979878","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T02:45:14Z","timestamp":1773024314000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1155\/ijog\/9979878"}},"subtitle":[],"editor":[{"given":"Julie","family":"Van De Weghe","sequence":"additional","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2025,1]]},"references-count":51,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2025,1]]}},"alternative-id":["10.1155\/ijog\/9979878"],"URL":"https:\/\/doi.org\/10.1155\/ijog\/9979878","archive":["Portico"],"relation":{},"ISSN":["2314-436X","2314-4378"],"issn-type":[{"value":"2314-436X","type":"print"},{"value":"2314-4378","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1]]},"assertion":[{"value":"2025-03-31","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-10-04","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-11-10","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"9979878"}}