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Skeletal aging is influenced by epigenetic mechanisms; however, the link to the epigenetic clocks, that is, the suggested biomarkers of biological aging intensively studied within aging research, remains largely unexplored. We investigated the association of eight epigenetic clocks\u2014Horvath, IEAA, Hannum, EEAA, PhenoAge, GrimAge, DunedinPoAm, DunedinPACE\u2014and methylation\u2010based telomere length (mTL) measured at intake (1997, 2007, or 2008\u201311) with register\u2010based incident fracture and osteoporosis diagnoses in 310 (Discovery cohort), and 777 (Replication cohort) twins, derived from nationwide population\u2010based surveys (end\u2010of\u2010follow\u2010up: 2022). For the 288 youngest twins, bone mineral density (BMD), and bone turnover markers C\u2010terminal telopeptide (CTX) and amino pro\u2010collagen type 1\u2009N\u2010terminal propeptide (P1NP) were available. Analyses were conducted at both the individual and twin\u2010pair levels, reducing genetic and environmental confounding. A consistent pattern emerged: increased epigenetic age, faster pace of aging, and shorter mTL associated with a higher risk of fractures, or osteoporosis. Notably, DunedinPoAm, DuninPACE, and GrimAge demonstrated the most robust associations. DuninPACE displayed the largest effects; hazard ratios ranging from 1.29 to 3.17, reflecting a 29%\u2013217% increased hazard for diagnosis pr. one standard deviation increase in DuninPACE. The same directions of effects were seen for decreasing CTX and P1NP levels, suggesting bone remodeling impairment for individuals with higher biological age. Lastly, sex\u2010 and age\u2010specific analysis of BMD indicated the same direction of effect for DunedinPoAm, and GrimAge in older females. These findings suggest that epigenetic clocks may serve as biomarkers for bone aging.<\/jats:p>","DOI":"10.1111\/acel.70204","type":"journal-article","created":{"date-parts":[[2025,9,15]],"date-time":"2025-09-15T01:15:13Z","timestamp":1757898913000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Epigenetic Clocks as Biomarkers for Bone Aging: Evidence From a Twin Study"],"prefix":"10.1111","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5268-3366","authenticated-orcid":false,"given":"Mette","family":"Soerensen","sequence":"first","affiliation":[{"name":"The Danish Twin Registry and the Research Unit for Epidemiology, Biostatistics, and Biodemography, Department of Public Health University of Southern Denmark  Odense Denmark"},{"name":"Department of Clinical Genetics Odense University Hospital  Odense Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florence","family":"Figeac","sequence":"additional","affiliation":[{"name":"Molecular Endocrinology Department, Department of Endocrinology Odense University Hospital  Odense Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaare","family":"Christensen","sequence":"additional","affiliation":[{"name":"The Danish Twin Registry and the Research Unit for Epidemiology, Biostatistics, and Biodemography, Department of Public Health University of Southern Denmark  Odense Denmark"},{"name":"Department of Clinical Genetics Odense University Hospital  Odense Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moustapha","family":"Kassem","sequence":"additional","affiliation":[{"name":"Molecular Endocrinology Department, Department of Endocrinology Odense University Hospital  Odense Denmark"},{"name":"Department of Cellular and Molecular Medicine, Faculty of Health, and Medical Sciences University of Copenhagen  Copenhagen Denmark"},{"name":"College of Medicine and Health Sciences and Center for Biotechnology Khalifa University  Abu Dhabi UAE"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,9,14]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2005.12.082"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.3354"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.54870"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.73420"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.18632\/aging.101020"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.2147\/CLEP.S20247"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.2147\/CLEP.S444447"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/bmb\/ldaa005"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(18)32112\u20103"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00198\u2010004\u20101689\u2010z"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1080\/15592294.2016.1271854"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.3298"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2012.0095"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.maturitas.2022.06.014"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2012.10.016"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/s43587\u2010022\u201000248\u20102"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1186\/gb\u20102013\u201014\u201010\u2010r115"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1474\u20109726.2011.00669.x"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.18632\/aging.101414"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bty532"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.18632\/aging.101684"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.18632\/aging.102173"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/acel.14135"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1210\/er.2009\u20100024"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1159\/000534561"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1017\/thg.2019.72"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(10)62349\u20105"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiae016"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyw307"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1097\/HS9.0000000000000768"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2003.07.005"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.202302665R"}],"container-title":["Aging 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