{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T02:21:00Z","timestamp":1790994060583,"version":"4.1.0"},"reference-count":95,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2019,10,1]],"date-time":"2019-10-01T00:00:00Z","timestamp":1569888000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Introduction: Osteoporosis is increasingly prevalent in the elderly, with fractures mostly occurring in women and men who are older than 55 and 65 years of age, respectively. The aim of this review was to examine the evidence regarding the influence of hormones on bone metabolism, followed by clinical data of hormonal changes in the elderly, in the attempt to provide possible poorly explored diagnostic and therapeutic candidate targets for the management of primary osteoporosis in the aging population. Material and methods: An extensive Medline search using PubMed, Embase, and Cochrane Library was performed. Results: While the rise in Thyroid-stimulating hormone (TSH) levels has a protective role on bone mass, the decline of estrogen, testosterone, Insulin-like growth factor 1 (IGF1), and vitamin D and the rise of cortisol, parathyroid hormone, and follicle-stimulating hormone (FSH) favor bone loss in the elderly. Particularly, the AA rs6166 FSH receptor (FSHR) genotype, encoding for a more sensitive FSHR than that encoded by the GG one, is associated with low total body mass density (BMD), independently of circulating estrogen. A polyclonal antibody with a FSHR-binding sequence against the \u03b2-subunit of murine FSH seems to be effective in ameliorating bone loss in ovariectomized mice. Conclusions: A complete hormonal assessment should be completed for both women and men during bone loss evaluation. Novel possible diagnostic and therapeutic tools might be developed for the management of male and female osteoporosis.<\/jats:p>","DOI":"10.3390\/jcm8101564","type":"journal-article","created":{"date-parts":[[2019,10,1]],"date-time":"2019-10-01T11:11:16Z","timestamp":1569928276000},"page":"1564","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":65,"title":["Osteoporosis from an Endocrine Perspective: The Role of Hormonal Changes in the Elderly"],"prefix":"10.3390","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4599-8487","authenticated-orcid":false,"given":"Rossella","family":"Cannarella","sequence":"first","affiliation":[{"name":"Department of Clinical and Experimental Medicine, University of Catania, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federica","family":"Barbagallo","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, University of Catania, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5217-9343","authenticated-orcid":false,"given":"Rosita A.","family":"Condorelli","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, University of Catania, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2989-2618","authenticated-orcid":false,"given":"Antonio","family":"Aversa","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Medicine, University Magna Graecia of Catanzaro, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7113-2372","authenticated-orcid":false,"given":"Sandro","family":"La Vignera","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, University of Catania, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6950-335X","authenticated-orcid":false,"given":"Aldo E.","family":"Calogero","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, University of Catania, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,10,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1016\/0002-9343(93)90218-E","article-title":"Consensus development conference: Diagnosis, prophylaxis, and treatment of osteoporosis","volume":"94","author":"Consensus","year":"1993","journal-title":"Am. J. Med."},{"key":"ref_2","unstructured":"World Health Organization (1992, January 22\u201324). Assessment of Fracture Risk and its Application to Screening for Postmenopausal Osteoporosis: Report of a WHO Study Group. Proceedings of World Health Organization Technical Report Series, Rome, Italy."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1210\/edrv-7-4-379","article-title":"Normal and pathological remodeling of human trabecular bone: Three dimensional reconstruction of the remodeling sequence in normals and in metabolic bone disease","volume":"7","author":"Eriksen","year":"1976","journal-title":"Endocr. Rev."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1038\/206489a0","article-title":"Suggested sequential mode of control of changes in cell behaviour in adult bone remodelling","volume":"206","author":"Hattner","year":"1965","journal-title":"Nature"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1002\/ar.1092260402","article-title":"Skeletal structural adaptations to mechanical usage (SATMU): 1. Redefining Wolff\u2019s law: The bone modeling problem","volume":"226","author":"Frost","year":"1990","journal-title":"Anat. Rec."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/S8756-3282(02)00947-X","article-title":"Trabecular minimodeling in human iliac bone","volume":"32","author":"Kobayashi","year":"2003","journal-title":"Bone"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1016\/S0140-6736(18)32112-3","article-title":"Osteoporosis","volume":"393","author":"Compston","year":"2019","journal-title":"Lancet"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1007\/s12519-018-0198-7","article-title":"An update on the role of RANKL-RANK\/osteoprotegerin and WNT-\u00df-catenin signaling pathways in pediatric diseases","volume":"15","author":"Brunetti","year":"2019","journal-title":"World J. Pediatr."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"13960","DOI":"10.1073\/pnas.251534698","article-title":"Up-regulation of TNF-producing T cells in the bone marrow: A key mechanism by which estrogen deficiency induces bone loss in vivo","volume":"98","author":"Roggia","year":"2001","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"10405","DOI":"10.1073\/pnas.1533207100","article-title":"Estrogen deficiency induces bone loss by increasing T cell proliferation and lifespan through IFN-gamma-induced class II transactivator","volume":"100","author":"Cenci","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"750","DOI":"10.7326\/0003-4819-130-9-199905040-00016","article-title":"The effect of thyroid hormone on skeletal integrity","volume":"130","author":"Greenspan","year":"1999","journal-title":"Ann. Intern. Med."},{"key":"ref_12","first-page":"1132","article-title":"Bone changes in adult patients with abnormal thyroid function (with special reference to 45Ca kinetics and quantitative histology)","volume":"60","author":"Bordier","year":"1967","journal-title":"Proc. R. Soc. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1873","DOI":"10.1210\/endo-120-5-1873","article-title":"Thyroid hormone stimulates alkaline phosphatase activity in cultured rat osteoblastic cells (ROS 17\/2.8) through 3,5,3\u2019-triiodo-L-thyronine nuclear receptors","volume":"120","author":"Sato","year":"1987","journal-title":"Endocrinology"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1210\/endo.134.1.8275930","article-title":"Osteoblasts mediate thyroid hormone stimulation of osteoclastic bone resorption","volume":"134","author":"Britto","year":"1994","journal-title":"Endocrinology"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1329","DOI":"10.1101\/gad.13.10.1329","article-title":"Mice devoid of all known thyroid hormone receptors are viable but exhibit disorders of the pituitary-thyroid axis, growth, and bone maturation","volume":"13","author":"Wang","year":"1999","journal-title":"Genes Dev."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/S0092-8674(03)00771-2","article-title":"TSH is a negative regulator of skeletal remodeling","volume":"115","author":"Abe","year":"2003","journal-title":"Cell"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"70","DOI":"10.4103\/CJP.CJP_7_19","article-title":"Different susceptibilities of osteoclasts and osteoblasts to glucocorticoid-induced oxidative stress and mitochondrial alterations","volume":"62","author":"Chen","year":"2019","journal-title":"Chin. J. Physiol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1080\/10799893.2019.1625061","article-title":"Dexamethasone suppresses osteogenesis of osteoblast via the PI3K\/Akt signaling pathway in vitro and in vivo","volume":"39","author":"Pan","year":"2019","journal-title":"J. Recept. Signal Transduct. Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s11914-019-00498-x","article-title":"Glucocorticoid-Induced Osteoporosis: New Insights into the Pathophysiology and Treatments","volume":"17","author":"Lane","year":"2019","journal-title":"Curr. Osteoporos. Rep."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1016\/j.bbrc.2019.02.118","article-title":"Glucocorticoid induces osteonecrosis of the femoral head in rats through GSK3\u03b2-mediated osteoblast apoptosis","volume":"511","author":"Nie","year":"2019","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"8782","DOI":"10.1073\/pnas.0912176107","article-title":"ACTH protects against glucocorticoid-induced osteonecrosis of bone","volume":"107","author":"Zaidi","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1072","DOI":"10.1038\/labinvest.2017.62","article-title":"Adrenocorticotropic hormone and 1,25-dihydroxyvitamin D3 enhance human osteogenesis in vitro by synergistically accelerating the expression of bone-specific genes","volume":"97","author":"Tourkova","year":"2017","journal-title":"Lab. Investig."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1111\/j.1749-6632.2009.05231.x","article-title":"ACTH is a novel regulator of bone mass","volume":"1192","author":"Isales","year":"2010","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"7829","DOI":"10.1073\/pnas.130200197","article-title":"Estrogens suppress RANK ligand-induced osteoclast differentiation via a stromal cell independent mechanism involving c-Jun repression","volume":"97","author":"Shevde","year":"2000","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"8836","DOI":"10.1074\/jbc.M010764200","article-title":"Estrogen decreases osteoclast formation by down-regulating receptor activator of NF-kappa B ligand (RANKL)-induced JNK activation","volume":"276","author":"Srivastava","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1016\/j.cell.2007.07.025","article-title":"Estrogen prevents bone loss via estrogen receptor alpha and induction of Fas ligand in osteoclasts","volume":"130","author":"Nakamura","year":"2007","journal-title":"Cell"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1172\/JCI65910","article-title":"Estrogen receptor-alpha signaling in osteoblast progenitors stimulates cortical bone accrual","volume":"123","author":"Almeida","year":"2013","journal-title":"J. Clin. Investig."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"6460","DOI":"10.1038\/s41598-017-06614-0","article-title":"Estrogen Regulates Bone Turnover by Targeting RANKL Expression in Bone Lining Cells","volume":"7","author":"Streicher","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1016\/j.bone.2012.08.111","article-title":"Androgen prevents hypogonadal bone loss via inhibition of resorption mediated by mature osteoblasts\/osteocytes","volume":"51","author":"Wiren","year":"2012","journal-title":"Bone"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1615\/CritRevEukaryotGeneExpr.v12.i2.10","article-title":"Estrogen receptors in skeletal metabolism: Lessons from genetically modified models of receptor function","volume":"12","author":"McCauley","year":"2002","journal-title":"Crit. Rev. Eukaryot. Gene Expr."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/S1043-2760(02)00594-5","article-title":"Elucidation of estrogen receptor function in bone with the use of mouse models","volume":"13","author":"Windahl","year":"2002","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1677\/joe.0.1710229","article-title":"Estrogen receptor specificity in the regulation of the skeleton in female mice","volume":"171","author":"Lindberg","year":"2001","journal-title":"J. Endocrinol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1016\/8756-3282(96)00045-2","article-title":"Ovariectomy-induced high turnover in cortical bone is dependent on pituitary hormone in rats","volume":"18","author":"Yeh","year":"1996","journal-title":"Bone"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1016\/S8756-3282(97)00027-6","article-title":"Effects of 17 beta-estradiol administration on cortical and cancellous bone of ovariectomized rats with and without hypophysectomy","volume":"20","author":"Yeh","year":"1997","journal-title":"Bone"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/j.cell.2006.01.051","article-title":"FSH directly regulates bone mass","volume":"125","author":"Sun","year":"2006","journal-title":"Cell"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"14574","DOI":"10.1073\/pnas.1212806109","article-title":"Blocking antibody to the \u03b2-subunit of FSH prevents bone loss by inhibiting bone resorption and stimulating bone synthesis","volume":"109","author":"Zhu","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"3555","DOI":"10.1210\/en.2003-0036","article-title":"Luteinizing hormone receptor knockout (LuRKO) mice and transgenic human chorionic gonadotropin (hCG) overexpressing mice (hCG\u03b1\u03b2+) have bone phenotypes","volume":"144","author":"Yarram","year":"2003","journal-title":"Endocrinology"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.coph.2015.03.005","article-title":"Parathyroid hormone: Anabolic and catabolic actions on the skeleton","volume":"22","author":"Silva","year":"2015","journal-title":"Curr. Opin. Pharmacol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/j.pbiomolbio.2006.02.016","article-title":"Vitamin D physiology","volume":"92","author":"Lips","year":"2006","journal-title":"Prog. Biophys. Mol. Biol."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Gardinier, J.D., Daly-Seiler, C., Rostami, N., Kundal, S., and Zhang, C. (2019). Loss of the PTH\/PTHrP receptor along the osteoblast lineage limits the anabolic response to exercise. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0211076"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1008","DOI":"10.1210\/en.2012-1542","article-title":"Vitamin D receptor in osteoblasts is a negative regulator of bone mass control","volume":"154","author":"Yamamoto","year":"2013","journal-title":"Endocrinology"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1297","DOI":"10.1002\/jbmr.3096","article-title":"VDR in Osteoblast-Lineage Cells Primarily Mediates Vitamin D Treatment-Induced Increase in Bone Mass by Suppressing Bone Resorption","volume":"32","author":"Nakamichi","year":"2017","journal-title":"J. Bone Miner. Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1530\/JME-17-0298","article-title":"Insulin-like growth factors: Actions on the skeleton","volume":"61","author":"Yakar","year":"2018","journal-title":"J. Mol. Endocrinol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1111\/j.1365-2265.1977.tb01340.x","article-title":"The spectrum of thyroid disease in a community: The Whickham survey","volume":"7","author":"Tunbridge","year":"1977","journal-title":"Clin. Endocrinol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1210\/jcem.87.2.8182","article-title":"Serum TSH, T (4), and thyroid antibodies in the United States population (1988 to 1994): National Health and Nutrition Examination Survey (NHANES III)","volume":"87","author":"Hollowell","year":"2002","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1554","DOI":"10.1210\/jc.2011-3020","article-title":"Age-related changes in thyroid function: A longitudinal study of a community-based cohort","volume":"97","author":"Bremner","year":"2012","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"862","DOI":"10.1210\/jc.2011-2684","article-title":"Osteoporotic Fractures in Men (MrOS) Study. Thyroid function and mortality in older men: A prospective study","volume":"97","author":"Waring","year":"2012","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"4575","DOI":"10.1210\/jc.2007-1499","article-title":"Age-specific distribution of serum thyrotropin and antithyroid antibodies in the US population: Implications for the prevalence of subclinical hypothyroidism","volume":"92","author":"Surks","year":"2007","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1111\/cen.13440","article-title":"Prevalence of treated hypothyroidism in the community: Analysis from general practices in North-East England with implications for the United Kingdom","volume":"87","author":"Ingoe","year":"2017","journal-title":"Clin. Endocrinol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1111\/j.1365-2796.1991.tb00368.x","article-title":"High incidence of multinodular toxic goitre in the elderly population in a low iodine intake area vs. high incidence of Graves\u2019 disease in the young in a high iodine intake area: Comparative surveys of thyrotoxicosis epidemiology in East-Jutland Denmark and Iceland","volume":"229","author":"Laurberg","year":"1991","journal-title":"J. Intern. Med."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1097\/01.med.0000433055.99570.52","article-title":"The aging thyroid","volume":"20","author":"Tabatabaie","year":"2013","journal-title":"Curr. Opin. Endocrinol. Diabetes Obes."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"54","DOI":"10.3389\/fendo.2019.00054","article-title":"Adrenal Aging and Its Implications on Stress Responsiveness in Humans","volume":"10","author":"Yiallouris","year":"2019","journal-title":"Front. Endocrinol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1093\/geronb\/gbq049","article-title":"Frontiers in the Use of Biomarkers of Health in Research on Stress and Aging","volume":"65","author":"Piazza","year":"2010","journal-title":"J. Gerontol. B Psychol. Sci. Soc. Sci."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"3167","DOI":"10.1016\/j.psyneuen.2013.09.008","article-title":"Diurnal profiles of salivary cortisol and alpha-amylase change across the adult lifespan: Evidence from repeated daily life assessments","volume":"38","author":"Nater","year":"2013","journal-title":"Psychoneuroendocrinology"},{"key":"ref_55","first-page":"2468","article-title":"Effects of gender and age on the levels and circadian rhythmicity of plasma cortisol","volume":"81","author":"Leproult","year":"1996","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_56","first-page":"651","article-title":"Neuroendocrine rhythms and sleep in aging men","volume":"260","author":"Mockel","year":"1991","journal-title":"Am. J. Physiol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/j.exger.2007.06.010","article-title":"Neuroendocrine features in extreme longevity","volume":"43","author":"Ferrari","year":"2008","journal-title":"Exp. Gerontol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1016\/S2213-8587(18)30026-3","article-title":"The physiology of endocrine systems with aging","volume":"6","author":"Kaufman","year":"2018","journal-title":"Lancet Diabetes Endocrinol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1530\/eje.0.1440319","article-title":"Age-related changes of the hypothalamic-pituitary-adrenal axis: Pathophysiological correlates","volume":"144","author":"Ferrari","year":"2001","journal-title":"Eur. J. Endocrinol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1210\/jcem.87.2.8201","article-title":"Age trends in the level of serum testosterone and other hormones in middle-aged men: Longitudinal results from the Massachusetts male aging study","volume":"87","author":"Feldman","year":"2002","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"975","DOI":"10.1016\/j.exger.2004.03.023","article-title":"The health of normally aging men: The Massachusetts Male Aging Study (1987\u20132004)","volume":"39","author":"Araujo","year":"2004","journal-title":"Exp. Gerontol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1258\/acb.2010.010150","article-title":"Biochemical endocrinology of the hypogonadal male","volume":"47","author":"Belchetz","year":"2010","journal-title":"Ann. Clin. Biochem."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1016","DOI":"10.1210\/jcem-73-5-1016","article-title":"Age, disease, and changing sex hormone levels in middle-aged men: Results of the Massachusetts Male Aging Study","volume":"73","author":"Gray","year":"1991","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1210\/jc.2006-1859","article-title":"The relative contributions of aging, health, and lifestyle factors to serum testosterone decline in men","volume":"92","author":"Travison","year":"2007","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/ijir.2008.41","article-title":"ISA, ISSAM, EAU, EAA and ASA recommendations: Investigation, treatment and monitoring of late-onset hypogonadism in males","volume":"21","author":"Wang","year":"2009","journal-title":"Int. J. Impot. Res."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1056\/NEJMoa0911101","article-title":"Identification of late-onset hypogonadism in middle-aged and elderly men","volume":"363","author":"Wu","year":"2010","journal-title":"N. Engl. J. Med."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1508","DOI":"10.1210\/jc.2011-2513","article-title":"Characteristics of androgen deficiency in late-onset hypogonadism: Results from the European Male Aging Study (EMAS)","volume":"97","author":"Tajar","year":"2012","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1095\/biolreprod31.4.785","article-title":"Quantification of the human Sertoli cell population: Its distribution, relation to germ cell numbers, and age-related decline","volume":"31","author":"Johnson","year":"1984","journal-title":"Biol. Reprod."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"756","DOI":"10.1210\/jcem-59-4-756","article-title":"Leydig cell numbers, daily sperm production, and serum gonadotropin levels in aging men","volume":"59","author":"Neaves","year":"1984","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"192","DOI":"10.4103\/1008-682X.122336","article-title":"Late-onset hypogonadism: Current concepts and controversies of pathogenesis, diagnosis and treatment","volume":"16","author":"Huhtaniemi","year":"2014","journal-title":"Asian J. Androl."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/S0140-6736(09)60507-9","article-title":"Hyperparathyroidism","volume":"374","author":"Fraser","year":"2009","journal-title":"Lancet"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1016\/S0140-6736(70)91344-9","article-title":"Effect of age on calcium absorption","volume":"2","author":"Bullamore","year":"1970","journal-title":"Lancet"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1536","DOI":"10.1172\/JCI112134","article-title":"Aging decreases the capacity of human skin to produce vitamin D3","volume":"76","author":"MacLaughlin","year":"1985","journal-title":"J. Clin. Investig."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1703","DOI":"10.1172\/JCI27793","article-title":"Steroid and xenobiotic receptor and vitamin D receptor crosstalk mediates CYP24 expression and drug induced osteomalacia","volume":"116","author":"Zhou","year":"2006","journal-title":"J. Clin. Investig."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1093\/ageing\/13.1.14","article-title":"Renal impairment and its effects on calcium metabolism in elderly women","volume":"13","author":"Francis","year":"1984","journal-title":"Age Ageing"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1595","DOI":"10.1210\/jc.2019-00221","article-title":"Pharmacological Management of Osteoporosis in Postmenopausal Women: An Endocrine Society Clinical Practice Guideline","volume":"104","author":"Eastell","year":"2019","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1016\/8756-3282(86)90001-3","article-title":"The influence of age on bone mineral regulating hormones","volume":"7","author":"Epstein","year":"1986","journal-title":"Bone"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1177","DOI":"10.1152\/ajprenal.00038.2006","article-title":"Age-dependent alterations in Ca2+ homeostasis: Role of TRPV5 and TRPV6","volume":"291","author":"Huybers","year":"2006","journal-title":"Am. J. Physiol. Renal. Physiol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1093\/gerona\/54.12.B521","article-title":"Pleiotropic effects of growth hormone and insulin-like growth factor (IGF)-1 on biological aging: Inferences from moderate caloric-restricted animals","volume":"54","author":"Sonntag","year":"1999","journal-title":"J. Gerontol. A Biol. Sci. Med. Sci."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"e898","DOI":"10.1038\/tp.2016.167","article-title":"Insulin-like growth factor 1 and risk of depression in older people: The English Longitudinal Study of Ageing","volume":"6","author":"Chigogora","year":"2016","journal-title":"Transl. Psychiatry"},{"key":"ref_81","first-page":"837187","article-title":"Bone demineralization in postmenopausal women: Role of anamnestic risk factors","volume":"2012","author":"Condorelli","year":"2012","journal-title":"Int. J. Endocrinol."},{"key":"ref_82","first-page":"475","article-title":"L-thyroxin treatment and post-menopausal osteoporosis: Relevance of the risk profile present in clinical history","volume":"60","author":"Vicari","year":"2008","journal-title":"Minerva Ginecol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/S0002-9343(99)00420-9","article-title":"Apoptosis and osteoporosis","volume":"108","author":"Weinstein","year":"2000","journal-title":"Am. J. Med."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1802","DOI":"10.1210\/jc.2011-3045","article-title":"Endocrine Society. Osteoporosis in men: An Endocrine Society clinical practice guideline","volume":"97","author":"Watts","year":"2012","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_85","first-page":"4257","article-title":"Association between insulin-like growth factor I and bone mineral density in older women and men: The Framingham Heart Study","volume":"83","author":"Langlois","year":"1998","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1526","DOI":"10.1359\/jbmr.2000.15.8.1526","article-title":"Biochemical markers of bone turnover, endogenous hormones and the risk of fractures in postmenopausal women: The OFELY study","volume":"15","author":"Garnero","year":"2000","journal-title":"J. Bone Miner. Res."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1007\/s00223-003-0090-9","article-title":"Insulin-like growth factor I is a determinant of hip bone mineral density in men less than 60 years of age: MINOS study","volume":"74","author":"Szulc","year":"2004","journal-title":"Calcif. Tiss. Int."},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Wang, J., Zhang, W., Yu, C., Zhang, X., Zhang, H., Guan, Q., Zhao, J., and Xu, J. (2015). Follicle-Stimulating Hormone Increases the Risk of Postmenopausal Osteoporosis by Stimulating Osteoclast Differentiation. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0134986"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1628","DOI":"10.1359\/JBMR.040710","article-title":"Bone remodeling increases substantially in the years after menopause and remains increased in older osteoporosis patients","volume":"19","author":"Recker","year":"2004","journal-title":"J. Bone Miner. Res."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1530\/EJE-10-0043","article-title":"FSHR gene polymorphisms influence bone mineral density and bone turnover in postmenopausal women","volume":"163","author":"Rendina","year":"2010","journal-title":"Eur. J. Endocrinol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1111\/j.1365-2265.2007.03005.x","article-title":"The relationship between gonadotrophins, gonadal hormones and bone mass in men","volume":"68","author":"Karim","year":"2008","journal-title":"Clin. Endocrinol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1701","DOI":"10.1002\/jbmr.2493","article-title":"Reproductive Hormones and Longitudinal Change in Bone Mineral Density and Incident Fracture Risk in Older Men: The Concord Health and Aging in Men Project","volume":"30","author":"Hsu","year":"2015","journal-title":"J. Bone Miner. Res."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1007\/s40618-016-0541-6","article-title":"Klinefelter syndrome (KS): Genetics, clinical phenotype and hypogonadism","volume":"40","author":"Bonomi","year":"2016","journal-title":"J. Endocrinol. Investig."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"596","DOI":"10.2174\/0929867321666141106125051","article-title":"Glucocorticoids in Patients with Rheumatic Diseases: Friends or Enemies of Bone?","volume":"22","author":"Ciccarelli","year":"2015","journal-title":"Curr. Med. Chem."},{"key":"ref_95","doi-asserted-by":"crossref","unstructured":"Ginaldi, L., De Martinis, M., Ciccarelli, F., Saitta, S., Imbesi, S., Mannucci, C., and Gangemi, S. (2015). Increased levels of interleukin 31 (IL-31) in osteoporosis. BMC Immunol., 16.","DOI":"10.1186\/s12865-015-0125-9"}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/8\/10\/1564\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T13:26:35Z","timestamp":1760189195000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/8\/10\/1564"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,10,1]]},"references-count":95,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2019,10]]}},"alternative-id":["jcm8101564"],"URL":"https:\/\/doi.org\/10.3390\/jcm8101564","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,10,1]]}}}