{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T05:00:12Z","timestamp":1787029212824,"version":"build-2736575974"},"reference-count":33,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2023,9,12]],"date-time":"2023-09-12T00:00:00Z","timestamp":1694476800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institutes of Health","award":["UL1TR001102"],"award-info":[{"award-number":["UL1TR001102"]}]},{"name":"National Institutes of Health","award":["UL1TR000170"],"award-info":[{"award-number":["UL1TR000170"]}]},{"name":"National Institutes of Health","award":["UL1RR025758"],"award-info":[{"award-number":["UL1RR025758"]}]},{"name":"National Institutes of Health","award":["M01RR01066"],"award-info":[{"award-number":["M01RR01066"]}]},{"name":"National Institutes of Health","award":["R01DK062249"],"award-info":[{"award-number":["R01DK062249"]}]},{"name":"National Institutes of Health","award":["R01MH083657"],"award-info":[{"award-number":["R01MH083657"]}]},{"name":"National Institutes of Health","award":["R01DK052625"],"award-info":[{"award-number":["R01DK052625"]}]},{"name":"National Institutes of Health","award":["R01HD060827"],"award-info":[{"award-number":["R01HD060827"]}]},{"name":"National Institutes of Health","award":["K23RR018851"],"award-info":[{"award-number":["K23RR018851"]}]},{"name":"National Institutes of Health","award":["K24HD071843"],"award-info":[{"award-number":["K24HD071843"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Our objective was to characterize bone outcomes in adolescent and young adult women with atypical anorexia nervosa (AAN) compared to typical AN and normal-weight healthy controls (HC) based on DSM-5 criteria. Four hundred thirty-two participants (141 AN, 131 AAN and 160 HC), ages 12\u201321 years, underwent dual-energy X-ray absorptiometry for areal BMD, and a subset had high-resolution peripheral quantitative CT assessment of the distal radius and tibia for volumetric BMD (vBMD), bone geometry and microarchitecture, and microfinite element analysis for estimated strength. The groups did not differ for age, pubertal stage, menarcheal age or physical activity. BMI and bone outcomes overall were intermediate in AAN compared with AN and HC. This applied to spine, total hip and femoral neck BMD measures and many distal tibial measures. However, the mean whole-body less head BMD Z-score did not differ between AAN and AN, and it was lower in both vs. HC. Similarly, many distal radius measures did not differ between AAN vs. AN or HC but were lower in AN than HC. Lower BMI, lean mass and bone age, older menarcheal age and longer illness duration correlated with greater impairment of bone outcomes. These data indicate that individuals with AAN overall have bone outcomes that are intermediate between AN and HC.<\/jats:p>","DOI":"10.3390\/nu15183946","type":"journal-article","created":{"date-parts":[[2023,9,12]],"date-time":"2023-09-12T21:41:12Z","timestamp":1694554872000},"page":"3946","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Bone Density, Geometry, Structure and Strength Estimates in Adolescent and Young Adult Women with Atypical Anorexia Nervosa versus Typical Anorexia Nervosa and Normal-Weight Healthy Controls"],"prefix":"10.3390","volume":"15","author":[{"given":"Shubhangi","family":"Tuli","sequence":"first","affiliation":[{"name":"Neuroendocrine Unit, Massachusetts General Hospital and Harvard Medical School, 55 Fruit Street, Boston, MA 02114, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9729-4433","authenticated-orcid":false,"given":"Vibha","family":"Singhal","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"},{"name":"MGH Weight Center, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7123-0661","authenticated-orcid":false,"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":"Nupur","family":"Gupta","sequence":"additional","affiliation":[{"name":"Division of Adolescent Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathryn","family":"Brigham","sequence":"additional","affiliation":[{"name":"Division of Adolescent Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Rosenblum","sequence":"additional","affiliation":[{"name":"Division of Adolescent Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seda","family":"Ebrahimi","sequence":"additional","affiliation":[{"name":"Cambridge Eating Disorders Center, Cambridge, MA 02138, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kamryn","family":"Eddy","sequence":"additional","affiliation":[{"name":"Eating Disorders Clinical and Research Program, Massachusetts General Hospital, Boston, MA 02114, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen","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"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9405-2981","authenticated-orcid":false,"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":[[2023,9,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1002\/wps.20050","article-title":"The DSM-5: Classification and criteria changes","volume":"12","author":"Regier","year":"2013","journal-title":"World Psychiatry"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Sawyer, S.M., Whitelaw, M., Le Grange, D., Yeo, M., and Hughes, E.K. (2016). Physical and Psychological Morbidity in Adolescents with Atypical Anorexia Nervosa. Pediatrics, 137.","DOI":"10.1542\/peds.2015-4080"},{"key":"ref_3","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_4","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1016\/S2213-8587(13)70180-3","article-title":"Endocrine consequences of anorexia nervosa","volume":"2","author":"Misra","year":"2014","journal-title":"Lancet Diabetes Endocrinol."},{"key":"ref_5","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_6","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_7","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1016\/j.bone.2009.09.005","article-title":"Hormone predictors of abnormal bone microarchitecture in women with anorexia nervosa","volume":"46","author":"Lawson","year":"2010","journal-title":"Bone"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1016\/j.jadohealth.2018.12.008","article-title":"Long-term Skeletal Consequences of Anorexia Nervosa: A \u201cWake up Call\u201d","volume":"64","author":"DiVasta","year":"2019","journal-title":"J. Adolesc. Health"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2931","DOI":"10.1210\/jc.2005-2818","article-title":"Determinants of skeletal loss and recovery in anorexia nervosa","volume":"91","author":"Miller","year":"2006","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1007\/s00774-021-01211-8","article-title":"Predictors of bone mineral density in adolescents with atypical anorexia nervosa","volume":"39","author":"Akgul","year":"2021","journal-title":"J. Bone Miner. Metab."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1111\/cen.13960","article-title":"Bone mineral density and estimated hip strength in men with anorexia nervosa, atypical anorexia nervosa and avoidant\/restrictive food intake disorder","volume":"90","author":"Schorr","year":"2019","journal-title":"Clin. Endocrinol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1002\/eat.23048","article-title":"Comparisons of bone density and body composition among adolescents with anorexia nervosa and atypical anorexia nervosa","volume":"52","author":"Nagata","year":"2019","journal-title":"Int. J. Eat. Disord."},{"key":"ref_13","first-page":"57","article-title":"Vertebral Volumetric Bone Density and Strength Are Impaired in Women with Low-Weight and Atypical Anorexia Nervosa","volume":"102","author":"Bachmann","year":"2017","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Chevalley, T., and Rizzoli, R. (2022). Acquisition of peak bone mass. Best Pract. Res. Clin. Endocrinol. Metab., 36.","DOI":"10.1016\/j.beem.2022.101616"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1016\/j.jpeds.2016.09.056","article-title":"The Determinants of Peak Bone Mass","volume":"180","author":"Gordon","year":"2017","journal-title":"J. Pediatr."},{"key":"ref_16","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_17","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_18","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1016\/j.bone.2009.06.002","article-title":"Effects of rhIGF-1 administration on surrogate markers of bone turnover in adolescents with anorexia nervosa","volume":"45","author":"Misra","year":"2009","journal-title":"Bone"},{"key":"ref_19","unstructured":"Kuczmarski, R.J., Ogden, C.L., Guo, S.S., Grummer-Strawn, L.M., Flegal, K.M., Mei, Z., Wei, R., Curtin, L.R., Roche, A.F., and Johnson, C.L. (2002). 2000 CDC Growth Charts for the United States: Methods and Development, United States Department of Health and Human Services."},{"key":"ref_20","first-page":"62","article-title":"Modifiable Activity Questionnaire for Adolescents","volume":"29","author":"Aaron","year":"1997","journal-title":"Med. Sci. Sports Exerc."},{"key":"ref_21","unstructured":"(2023, March 03). Available online: https:\/\/zscore.research.chop.edu\/calcpedbonedens.php."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/j.jocd.2014.01.003","article-title":"Dual-energy X-ray absorptiometry interpretation and reporting in children and adolescents: The revised 2013 ISCD Pediatric Official Positions","volume":"17","author":"Crabtree","year":"2014","journal-title":"J. Clin. Densitom."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"De Souza, M.J., Nattiv, A., Joy, E., Misra, M., Williams, N.I., Mallinson, R.J., Gibbs, J.C., Olmsted, M., Goolsby, M., and Matheson, G. (2014). 2014 Female Athlete Triad Coalition Consensus Statement on Treatment and Return to Play of the Female Athlete Triad: 1st International Conference held in San Francisco, California, May 2012 and 2nd International Conference held in Indianapolis, Indiana, May 2013. Br. J. Sports Med., 48.","DOI":"10.1136\/bjsports-2013-093218"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1359\/jbmr.071108","article-title":"Finite element analysis based on in vivo HR-pQCT images of the distal radius is associated with wrist fracture in postmenopausal women","volume":"23","author":"Boutroy","year":"2008","journal-title":"J. Bone Miner. Res."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Singhal, V., Huynh, C., Nimmala, S., Mitchell, D.M., Pedreira, C.C., Bader, A., Flanders, K., Zheng, J., Bouxsein, M.L., and Misra, M. (2022). Load-to-strength ratio at the radius is higher in adolescent and young adult females with obesity compared to normal-weight controls. Bone, 164.","DOI":"10.1016\/j.bone.2022.116515"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/j.jbiomech.2019.04.042","article-title":"A single-spring model predicts the majority of variance in impact force during a fall onto the outstretched hand","volume":"90","author":"Johnston","year":"2019","journal-title":"J. Biomech."},{"key":"ref_27","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_28","doi-asserted-by":"crossref","unstructured":"Haines, M.S., Kimball, A., Dove, D., Chien, M., Strauch, J., Santoso, K., Meenaghan, E., Eddy, K., Fazeli, P.K., and Misra, M. (2023). Deficits in volumetric bone mineral density, bone microarchitecture, and estimated bone strength in women with atypical anorexia nervosa compared to healthy controls. Int. J. Eat. Disord., in press.","DOI":"10.1002\/eat.24014"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"R115","DOI":"10.1530\/JOE-16-0089","article-title":"Influence of body weight on bone mass, architecture and turnover","volume":"230","author":"Iwaniec","year":"2016","journal-title":"J. Endocrinol."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Chen, Y., Xiang, J., Wang, Z., Xiao, Y., Zhang, D., Chen, X., Li, H., Liu, M., and Zhang, Q. (2015). Associations of Bone Mineral Density with Lean Mass, Fat Mass, and Dietary Patterns in Postmenopausal Chinese Women: A 2-Year Prospective Study. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0137097"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1210\/edrv.23.3.0465","article-title":"Sex steroids and the construction and conservation of the adult skeleton","volume":"23","author":"Riggs","year":"2002","journal-title":"Endocr. Rev."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"4174","DOI":"10.1210\/jc.2012-2561","article-title":"Fractures in healthy females followed from childhood to early adulthood are associated with later menarcheal age and with impaired bone microstructure at peak bone mass","volume":"97","author":"Chevalley","year":"2012","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1413","DOI":"10.1210\/jc.2017-00131","article-title":"Functional Hypothalamic Amenorrhea: An Endocrine Society Clinical Practice Guideline","volume":"102","author":"Gordon","year":"2017","journal-title":"J. Clin. Endocrinol. Metab."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/15\/18\/3946\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:49:23Z","timestamp":1760129363000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/15\/18\/3946"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,9,12]]},"references-count":33,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2023,9]]}},"alternative-id":["nu15183946"],"URL":"https:\/\/doi.org\/10.3390\/nu15183946","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,9,12]]}}}