{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T06:04:28Z","timestamp":1791612268325,"version":"4.3.4"},"reference-count":28,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2022,4,15]],"date-time":"2022-04-15T00:00:00Z","timestamp":1649980800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,4,15]],"date-time":"2022-04-15T00:00:00Z","timestamp":1649980800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Endocrine"],"published-print":{"date-parts":[[2022,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Purpose<\/jats:title>\n                <jats:p>Patients with functional hypothalamic amenorrhea (FHA) could commonly have bone damage, often preceded by metabolic alterations due to a relative energy deficit state. To date, there are no markers capable of predicting osteopenia before it is manifested on DXA. Irisin is a myokine that promotes the differentiation of osteoblastic cells and appears to be inversely correlated with the incidence of bone fragility and fractures in postmenopausal women. The aim of this study was to measure irisin levels in FHA patients and to correlate it with bone density parameters.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Thirty-two patients with FHA and 19 matched controls underwent the same clinical and laboratory evaluation.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Irisin and body mass index (BMI) were significantly lower in the case group than in healthy controls (2.03\u2009\u00b1\u20090.12 vs. 2.42\u2009\u00b1\u20090.09 <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05 and 19.43\u2009\u00b1\u20092.26 vs. 22.72\u2009\u00b1\u20090.67 <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05, respectively). Additionally, total body mass density (BMD g\/cm<jats:sup>2<\/jats:sup>) was significantly lower in the case group than in the healthy controls (1.09\u2009\u00b1\u20090.08 vs. 1.14\u2009\u00b1\u20090.05, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05), without signs of osteopenia.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>The FHA group showed lower irisin levels associated with significantly reduced BMD parameters that did not reach the severity of osteopenia. Therefore, we could speculate that irisin could predict DXA results in assessing modifications of body composition parameters. Future research is warranted to study these parameters in a larger population to confirm our results, so that irisin could be used as a predictor and screening method for bone deprivation. Furthermore, irisin is strictly related to energy metabolism and could be an indirect marker of nutritional status in FHA patients, identifying earlier states of energy deficit.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s12020-022-03050-7","type":"journal-article","created":{"date-parts":[[2022,4,15]],"date-time":"2022-04-15T15:03:11Z","timestamp":1650034991000},"page":"168-176","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Circulating irisin levels in functional hypothalamic amenorrhea: a new bone damage index? A pilot study"],"prefix":"10.1007","volume":"77","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1124-6877","authenticated-orcid":false,"given":"Giovanna","family":"Notaristefano","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annamaria","family":"Merola","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa","family":"Scarinci","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicol\u00f2","family":"Ubaldi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monia","family":"Ranalli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Tropea","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alice","family":"Diterlizzi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simone Michele","family":"Fabozzi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ornella","family":"Alesiani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Silvestrini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alvaro","family":"Mordente","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esmeralda","family":"Capristo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Lanzone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosanna","family":"Apa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,4,15]]},"reference":[{"key":"3050_CR1","doi-asserted-by":"publisher","unstructured":"B. Meczekalski, K. Katulski, A. Czyzyk, et al. Functional hypothalamic amenorrhea and its influence on women\u2019s health. J. Endocrinol. Investig. 37, (2014) https:\/\/doi.org\/10.1007\/s40618-014-0169-3","DOI":"10.1007\/s40618-014-0169-3"},{"key":"3050_CR2","doi-asserted-by":"publisher","first-page":"1413","DOI":"10.1210\/jc.2017-00131","volume":"102","author":"CM Gordon","year":"2017","unstructured":"C.M. Gordon, K.E. Ackerman, S.L. Berga et al. Functional hypothalamic Amenorrhea: An endocrine society clinical practice guideline. J. Clin. Endocrinol. Metabol. 102, 1413\u20131439 (2017). https:\/\/doi.org\/10.1210\/jc.2017-00131","journal-title":"J. Clin. Endocrinol. Metabol."},{"key":"3050_CR3","doi-asserted-by":"publisher","unstructured":"N.J. Crabtree, A. Arabi, L.K. Bachrach, et al. Dual-energy X-Ray absorptiometry interpretation and reporting in children and adolescents: The Revised 2013 ISCD Pediatric Official Positions. J. Clin. Densitometry 17, (2014). https:\/\/doi.org\/10.1016\/j.jocd.2014.01.003","DOI":"10.1016\/j.jocd.2014.01.003"},{"key":"3050_CR4","doi-asserted-by":"publisher","unstructured":"A. Nattiv, A. Loucks, M. Manore, et al. The female athlete triad. Med. Sci. Sports Exer. 39, (2007) https:\/\/doi.org\/10.1249\/mss.0b013e318149f111","DOI":"10.1249\/mss.0b013e318149f111"},{"key":"3050_CR5","doi-asserted-by":"publisher","unstructured":"P. Lee, J.D. Linderman, S. Smith, et al. Irisin and FGF21 are cold-induced endocrine activators of brown fat function in humans. Cell Metabol. 19, (2014) https:\/\/doi.org\/10.1016\/j.cmet.2013.12.017","DOI":"10.1016\/j.cmet.2013.12.017"},{"key":"3050_CR6","doi-asserted-by":"publisher","first-page":"463","DOI":"10.1038\/nature10777","volume":"481","author":"P Bostr\u00f6m","year":"2012","unstructured":"P. Bostr\u00f6m, J. Wu, M.P. Jedrychowski et al. A PGC1-\u03b1-dependent myokine that drives brown-fat-like development of white fat and thermogenesis. Nature 481, 463\u2013468 (2012). https:\/\/doi.org\/10.1038\/nature10777","journal-title":"Nature"},{"key":"3050_CR7","doi-asserted-by":"publisher","first-page":"324","DOI":"10.1038\/nrendo.2016.221","volume":"13","author":"N Perakakis","year":"2017","unstructured":"N. Perakakis, G.A. Triantafyllou, J.M. Fern\u00e1ndez-Real et al. Physiology and role of irisin in glucose homeostasis. Nat. Rev. Endocrinol. 13, 324\u2013337 (2017). https:\/\/doi.org\/10.1038\/nrendo.2016.221","journal-title":"Nat. Rev. Endocrinol."},{"key":"3050_CR8","doi-asserted-by":"publisher","unstructured":"G. Colaianni, C. Cuscito, T. Mongelli, et al. Irisin enhances osteoblast differentiation In Vitro. Int. J. Endocrinol. (2014). https:\/\/doi.org\/10.1155\/2014\/902186","DOI":"10.1155\/2014\/902186"},{"key":"3050_CR9","doi-asserted-by":"publisher","unstructured":"Y. Ma, X. Qiao, R. Zeng, et al. Irisin promotes proliferation but inhibits differentiation in osteoclast precursor cells. FASEB J. 32, (2018). https:\/\/doi.org\/10.1096\/fj.201700983RR","DOI":"10.1096\/fj.201700983RR"},{"key":"3050_CR10","doi-asserted-by":"publisher","unstructured":"T. Klangjareonchai, H. Nimitphong, S. Saetung, et al. Circulating sclerostin and irisin are related and interact with gender to influence adiposity in adults with prediabetes. Int. J. Endocrinol. (2014). https:\/\/doi.org\/10.1155\/2014\/261545","DOI":"10.1155\/2014\/261545"},{"key":"3050_CR11","doi-asserted-by":"publisher","first-page":"1302","DOI":"10.1097\/GME.0000000000001388","volume":"26","author":"K Zhou","year":"2019","unstructured":"K. Zhou, X. Qiao, Y. Cai et al. Lower circulating irisin in middle-aged and older adults with osteoporosis: a systematic review and meta-analysis. Menopause 26, 1302\u20131310 (2019). https:\/\/doi.org\/10.1097\/GME.0000000000001388","journal-title":"Menopause"},{"key":"3050_CR12","doi-asserted-by":"publisher","first-page":"100218","DOI":"10.1371\/journal.pone.0100218","volume":"9","author":"V Singhal","year":"2014","unstructured":"V. Singhal, E.A. Lawson, K.E. Ackerman et al. Irisin levels are lower in young amenorrheic athletes compared with eumenorrheic athletes and non-athletes and are associated with bone density and strength estimates. PLoS ONE. 9, 100218 (2014). https:\/\/doi.org\/10.1371\/journal.pone.0100218","journal-title":"PLoS ONE."},{"key":"3050_CR13","doi-asserted-by":"publisher","first-page":"937","DOI":"10.1016\/j.metabol.2015.06.005","volume":"64","author":"SA Polyzos","year":"2015","unstructured":"S.A. Polyzos, C.S. Mantzoros, An update on the validity of irisin assays and the link between irisin and hepatic metabolism. Metabolism 64, 937\u2013942 (2015). https:\/\/doi.org\/10.1016\/j.metabol.2015.06.005","journal-title":"Metabolism"},{"key":"3050_CR14","doi-asserted-by":"publisher","first-page":"1910","DOI":"10.1210\/jc.2013-2373","volume":"98","author":"K Hee Park","year":"2013","unstructured":"K. Hee Park, L. Zaichenko, M. Brinkoetter et al. Circulating Irisin in relation to insulin resistance and the metabolic syndrome. J. Clin. Endocrinol. Metabol. 98, 1910 (2013). https:\/\/doi.org\/10.1210\/jc.2013-2373","journal-title":"J. Clin. Endocrinol. Metabol."},{"key":"3050_CR15","doi-asserted-by":"publisher","unstructured":"G. Colaianni, S. Cinti, S. Colucci, M. Grano. Irisin and musculoskeletal health. Ann. New York Acad. Sci. 1402, (2017). https:\/\/doi.org\/10.1111\/nyas.13345","DOI":"10.1111\/nyas.13345"},{"key":"3050_CR16","doi-asserted-by":"publisher","unstructured":"F. Norheim, T.M. Langleite, M. Hjorth, et al. (2014) The effects of acute and chronic exercise on PGC-1\u03b1, irisin and browning of subcutaneous adipose tissue in humans. FEBS J. 281. https:\/\/doi.org\/10.1111\/febs.12619","DOI":"10.1111\/febs.12619"},{"key":"3050_CR17","doi-asserted-by":"publisher","first-page":"584","DOI":"10.1210\/jc.2011-2246","volume":"97","author":"MA Bredella","year":"2012","unstructured":"M.A. Bredella, P.K. Fazeli, L.M. Freedman et al. Young women with cold-activated brown adipose tissue have higher bone mineral density and lower Pref-1 than women without brown adipose tissue: A study in women with anorexia nervosa, women recovered from anorexia nervosa, and normal-weight women. J. Clin. Endocrinol. Metabol. 97, 584\u2013590 (2012). https:\/\/doi.org\/10.1210\/jc.2011-2246","journal-title":"J. Clin. Endocrinol. Metabol."},{"key":"3050_CR18","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1042\/BJ20130457","volume":"453","author":"TJ Schulz","year":"2013","unstructured":"T.J. Schulz, Y.-H. Tseng, Brown adipose tissue: Development, metabolism and beyond. Biochem. J. 453, 167\u2013178 (2013). https:\/\/doi.org\/10.1042\/BJ20130457","journal-title":"Biochem. J."},{"key":"3050_CR19","doi-asserted-by":"crossref","unstructured":"H.S. Vassimon. Energy expenditure and substrate oxidation in subjects with human immunodeficiency virus treated with antiretroviral drugs. In: Health of HIV Infected People. Elsevier (2015).","DOI":"10.1016\/B978-0-12-800769-3.00025-1"},{"key":"3050_CR20","doi-asserted-by":"publisher","first-page":"1696","DOI":"10.1038\/ijo.2015.130","volume":"39","author":"MJ Vosselman","year":"2015","unstructured":"M.J. Vosselman, J. Hoeks, B. Brans et al. Low brown adipose tissue activity in endurance-trained compared with lean sedentary men. Int. J. Obes. 39, 1696\u20131702 (2015). https:\/\/doi.org\/10.1038\/ijo.2015.130","journal-title":"Int. J. Obes."},{"key":"3050_CR21","doi-asserted-by":"publisher","first-page":"202","DOI":"10.3389\/fendo.2013.00202","volume":"4","author":"T Hofmann","year":"2014","unstructured":"T. Hofmann, U. Elbelt, A. Ahnis et al. Irisin levels are not affected by physical activity in patients with anorexia nervosa. Front. Endocrinol. 4, 202 (2014). https:\/\/doi.org\/10.3389\/fendo.2013.00202","journal-title":"Front. Endocrinol."},{"key":"3050_CR22","doi-asserted-by":"publisher","first-page":"1725","DOI":"10.1016\/j.metabol.2012.09.002","volume":"61","author":"JY Huh","year":"2012","unstructured":"J.Y. Huh, G. Panagiotou, V. Mougios et al. FNDC5 and irisin in humans: I. Predictors of circulating concentrations in serum and plasma and II. mRNA expression and circulating concentrations in response to weight loss and exercise. Metabolism 61, 1725\u20131738 (2012). https:\/\/doi.org\/10.1016\/j.metabol.2012.09.002","journal-title":"Metabolism"},{"key":"3050_CR23","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1016\/j.peptides.2012.11.014","volume":"39","author":"A Stengel","year":"2013","unstructured":"A. Stengel, T. Hofmann, M. Goebel-Stengel et al. Circulating levels of irisin in patients with anorexia nervosa and different stages of obesity \u2013 Correlation with body mass index. Peptides 39, 125\u2013130 (2013). https:\/\/doi.org\/10.1016\/j.peptides.2012.11.014","journal-title":"Peptides"},{"key":"3050_CR24","doi-asserted-by":"publisher","first-page":"1633","DOI":"10.1007\/s00198-014-2673-x","volume":"25","author":"AD Anastasilakis","year":"2014","unstructured":"A.D. Anastasilakis, S.A. Polyzos, P. Makras et al. Circulating irisin is associated with osteoporotic fractures in postmenopausal women with low bone mass but is not affected by either teriparatide or denosumab treatment for 3 months. Osteoporosis Int. 25, 1633\u20131642 (2014). https:\/\/doi.org\/10.1007\/s00198-014-2673-x","journal-title":"Osteoporosis Int."},{"key":"3050_CR25","doi-asserted-by":"publisher","first-page":"2693","DOI":"10.1210\/jc.2012-1589","volume":"97","author":"S Ponrartana","year":"2012","unstructured":"S. Ponrartana, P.C. Aggabao, H.H. Hu et al. Brown adipose tissue and its relationship to bone structure in pediatric patients. Journal Clin. Endocrinol. Metabol. 97, 2693\u20132698 (2012). https:\/\/doi.org\/10.1210\/jc.2012-1589","journal-title":"Journal Clin. Endocrinol. Metabol."},{"key":"3050_CR26","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1210\/en.2007-0171","volume":"148","author":"BM Abdallah","year":"2007","unstructured":"B.M. Abdallah, M. Ding, C.H. Jensen et al. Dlk1\/FA1 is a novel endocrine regulator of bone and fat mass and its serum level is modulated by growth hormone. Endocrinology 148, 3 (2007). https:\/\/doi.org\/10.1210\/en.2007-0171","journal-title":"Endocrinology"},{"key":"3050_CR27","doi-asserted-by":"publisher","first-page":"1513","DOI":"10.1007\/s00198-012-2110-y","volume":"24","author":"P Lee","year":"2013","unstructured":"P. Lee, R.J. Brychta, M.T. Collins et al. Cold-activated brown adipose tissue is an independent predictor of higher bone mineral density in women. Osteoporosis Int. 24, 1513\u20131518 (2013). https:\/\/doi.org\/10.1007\/s00198-012-2110-y","journal-title":"Osteoporosis Int."},{"key":"3050_CR28","doi-asserted-by":"publisher","first-page":"274","DOI":"10.3390\/medicina56060274","volume":"56","author":"R Lagzdina","year":"2020","unstructured":"R. Lagzdina, M. Rumaka, G. Gersone, P. Tretjakovs, Circulating Irisin in healthy adults: Changes after acute exercise, correlation with body composition, and energy expenditure parameters in cross-sectional study. Medicina 56, 274 (2020). https:\/\/doi.org\/10.3390\/medicina56060274","journal-title":"Medicina"}],"container-title":["Endocrine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12020-022-03050-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s12020-022-03050-7\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12020-022-03050-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,7,20]],"date-time":"2022-07-20T17:17:57Z","timestamp":1658337477000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s12020-022-03050-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,4,15]]},"references-count":28,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2022,6]]}},"alternative-id":["3050"],"URL":"https:\/\/doi.org\/10.1007\/s12020-022-03050-7","relation":{},"ISSN":["1559-0100"],"issn-type":[{"value":"1559-0100","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,4,15]]},"assertion":[{"value":"30 November 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 March 2022","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 April 2022","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Compliance with Ethical Standards"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of Fondazione Policlinico Universitario A. Gemelli IRCCS (Date 19\/05\/2021\/No. 0018288\/21 ID 3956).","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"The study was approved by our local ethical committee and informed consent was obtained.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Research involving human participants and\/or animals"}},{"value":"Informed consent was obtained from all individual participants included in the study.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to participate"}}]}}