{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T00:08:48Z","timestamp":1793750928630,"version":"4.6.1"},"reference-count":18,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2022,6,21]],"date-time":"2022-06-21T00:00:00Z","timestamp":1655769600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["R01 DK062249"],"award-info":[{"award-number":["R01 DK062249"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["R0I HD060827"],"award-info":[{"award-number":["R0I HD060827"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["K24 HD071843"],"award-info":[{"award-number":["K24 HD071843"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["K23DK110419-01"],"award-info":[{"award-number":["K23DK110419-01"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["UL1TR001102"],"award-info":[{"award-number":["UL1TR001102"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background: While physiologic estrogen replacement results in increases in areal bone mineral density (aBMD) in hypoestrogenic adolescent girls and young adult women with AN, data are lacking regarding its impact on measures of volumetric BMD (vBMD), bone geometry, and structure. Methods: 23 young women with anorexia nervosa (AN) and 27 normal-weight healthy controls (HC) between 14\u201325 years old were followed for 12 months. AN participants received transdermal 17\u03b2-estradiol (continuously) with 10 days of cyclic oral progesterone (100 mg daily) every month for the study duration (AN-E+). DXA was used to measure aBMD and body composition, high resolution peripheral quantitative CT (HRpQCT) to assess vBMD, bone geometry and structure at the distal radius and tibia, and microfinite element analysis to estimate strength. Results: Groups did not differ for age. Median baseline BMI z-scores were \u22121.13 (\u22121.58, \u22120.38) in AN-E+ vs. 0.08 (\u22120.40, 0.84) in HC (p &lt; 0.0001). For most HRpQCT parameters and strength estimates, young women with AN receiving physiologic estrogen replacement demonstrated similar changes over 12 months as did normoestrogenic HC. Additionally, radial cortical tissue mineral density, cortical vBMD, and failure load increased (p = 0.01; p = 0.02; p = 0.004 respectively) over 12 months in AN-E+ compared to HC. Conclusions: With physiologic estrogen replacement, bone accrual improved in AN to approximate changes observed in normoestrogenic controls followed without any intervention, with additional benefits observed for cortical tissue mineral density, cortical vBMD, and failure load at the radius in AN vs. controls. Thus, this strategy for estrogen replacement effectively mimics the effects of endogenous estrogen on bone structure and estimated strength.<\/jats:p>","DOI":"10.3390\/nu14132557","type":"journal-article","created":{"date-parts":[[2022,6,22]],"date-time":"2022-06-22T04:12:01Z","timestamp":1655871121000},"page":"2557","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Physiologic Transdermal Estradiol Replacement Mimics Effects of Endogenous Estrogen on Bone Outcomes in Hypoestrogenic Women with Anorexia Nervosa"],"prefix":"10.3390","volume":"14","author":[{"given":"Vibha","family":"Singhal","sequence":"first","affiliation":[{"name":"Neuroendocrine Unit, Massachusetts General Hospital and Harvard Medical School, 55 Fruit Street, Boston, MA 02114, USA"},{"name":"Division of Pediatric Endocrinology, Massachusetts General Hospital and Harvard Medical School, 55 Fruit Street, Boston, MA 02114, USA"},{"name":"MGH Weight Center, Massachusetts General Hospital and Harvard Medical School, 55 Fruit Street, Boston, MA 02114, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4503-2570","authenticated-orcid":false,"given":"Supritha","family":"Nimmala","sequence":"additional","affiliation":[{"name":"Neuroendocrine Unit, Massachusetts General Hospital and Harvard Medical School, 55 Fruit Street, Boston, MA 02114, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meghan","family":"Slattery","sequence":"additional","affiliation":[{"name":"Neuroendocrine Unit, Massachusetts General Hospital and Harvard Medical School, 55 Fruit Street, Boston, MA 02114, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kamryn T.","family":"Eddy","sequence":"additional","affiliation":[{"name":"Neuroendocrine Unit, Massachusetts General Hospital and Harvard Medical School, 55 Fruit Street, Boston, MA 02114, USA"},{"name":"Eating Disorders Clinical and Research Program, Massachusetts General Hospital, Boston, MA 02114, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen K.","family":"Miller","sequence":"additional","affiliation":[{"name":"Neuroendocrine Unit, Massachusetts General Hospital and Harvard Medical School, 55 Fruit Street, Boston, MA 02114, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Klibanski","sequence":"additional","affiliation":[{"name":"Neuroendocrine Unit, Massachusetts General Hospital and Harvard Medical School, 55 Fruit Street, Boston, MA 02114, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madhusmita","family":"Misra","sequence":"additional","affiliation":[{"name":"Neuroendocrine Unit, Massachusetts General Hospital and Harvard Medical School, 55 Fruit Street, Boston, MA 02114, USA"},{"name":"Division of Pediatric Endocrinology, Massachusetts General Hospital and Harvard Medical School, 55 Fruit Street, Boston, MA 02114, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,6,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1007\/s007870200011","article-title":"Bone mineral density in adolescent girls with anorexia nervosa\u2014A cross-sectional study","volume":"11","author":"Jagielska","year":"2002","journal-title":"Eur. Child Adolesc. Psychiatry"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1574","DOI":"10.1542\/peds.2004-0540","article-title":"Effects of anorexia nervosa on clinical, hematologic, biochemical, and bone density parameters in community-dwelling adolescent girls","volume":"114","author":"Misra","year":"2004","journal-title":"Pediatrics"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/S1043-2760(00)00336-2","article-title":"Acquisition of optimal bone mass in childhood and adolescence","volume":"12","author":"Bachrach","year":"2001","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1231","DOI":"10.1210\/jc.2007-1434","article-title":"Weight gain and restoration of menses as predictors of bone mineral density change in adolescent girls with anorexia nervosa-1","volume":"93","author":"Misra","year":"2008","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"4177","DOI":"10.1210\/jc.2001-011889","article-title":"Abnormal Bone Mineral Accrual in Adolescent Girls with Anorexia Nervosa","volume":"87","author":"Soyka","year":"2002","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1002\/eat.22248","article-title":"Fracture risk and areal bone mineral density in adolescent females with anorexia nervosa","volume":"47","author":"Faje","year":"2014","journal-title":"Int. J. Eat. Disord."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1923","DOI":"10.1210\/jc.2012-4153","article-title":"Adolescent Girls with Anorexia Nervosa Have Impaired Cortical and Trabecular Microarchitecture and Lower Estimated Bone Strength at the Distal Radius","volume":"98","author":"Faje","year":"2013","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.bone.2017.07.009","article-title":"Impaired Bone Strength Estimates at the Distal Tibia and its Determinants in Adolescents with Anorexia Nervosa","volume":"106","author":"Singhal","year":"2018","journal-title":"Bone"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"938","DOI":"10.1148\/radiol.2492080173","article-title":"Distal radius in adolescent girls with anorexia nervosa: Trabecular structure analysis with high-resolution flat-panel volume CT","volume":"249","author":"Bredella","year":"2008","journal-title":"Radiology"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2430","DOI":"10.1002\/jbmr.447","article-title":"Physiologic estrogen replacement increases bone density in adolescent girls with anorexia nervosa","volume":"26","author":"Misra","year":"2011","journal-title":"J. Bone Miner. Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1542\/peds.109.1.45","article-title":"Centers for Disease Control and Prevention 2000 growth charts for the United States: Improvements to the 1977 National Center for Health Statistics version","volume":"109","author":"Ogden","year":"2002","journal-title":"Pediatrics"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/S1083-3188(02)00145-6","article-title":"The effect of estrogen-progestin treatment on bone mineral density in anorexia nervosa","volume":"15","author":"Golden","year":"2002","journal-title":"J. Pediatr. Adolesc. Gynecol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2021","DOI":"10.1210\/clinem\/dgab145","article-title":"Effect of Transdermal Estradiol and Insulin-like Growth Factor-1 on Bone Endpoints of Young Women with Anorexia Nervosa","volume":"106","author":"Singhal","year":"2021","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2087","DOI":"10.1210\/jc.2006-2553","article-title":"The bone mineral density in childhood study: Bone mineral content and density according to age, sex, and race","volume":"92","author":"Kalkwarf","year":"2007","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"842","DOI":"10.1016\/S8756-3282(02)00736-6","article-title":"Estimation of distal radius failure load with micro-finite element analysis models based on three-dimensional peripheral quantitative computed tomography images","volume":"30","author":"Pistoia","year":"2002","journal-title":"Bone"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1203","DOI":"10.1016\/j.bone.2008.01.017","article-title":"Bone strength at the distal radius can be estimated from high-resolution peripheral quantitative computed tomography and the finite element method","volume":"42","author":"MacNeil","year":"2008","journal-title":"Bone"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"R163","DOI":"10.1530\/JOE-14-0039","article-title":"Anorexia nervosa and bone","volume":"221","author":"Misra","year":"2014","journal-title":"J. Endocrinol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/S2213-8587(18)30308-5","article-title":"Cortical and trabecular bone microarchitecture as an independent predictor of incident fracture risk in older women and men in the Bone Microarchitecture International Consortium (BoMIC): A prospective study","volume":"7","author":"Samelson","year":"2019","journal-title":"Lancet Diabetes Endocrinol."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/14\/13\/2557\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:36:15Z","timestamp":1760139375000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/14\/13\/2557"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6,21]]},"references-count":18,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2022,7]]}},"alternative-id":["nu14132557"],"URL":"https:\/\/doi.org\/10.3390\/nu14132557","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,6,21]]}}}