{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T03:43:27Z","timestamp":1792640607287,"version":"4.5.0"},"reference-count":114,"publisher":"Bioscientifica","issue":"8","license":[{"start":{"date-parts":[[2023,5,11]],"date-time":"2023-05-11T00:00:00Z","timestamp":1683763200000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["ec.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2023,7,5]]},"abstract":"<jats:p>Low bone mass is common in men with Klinefelter syndrome (KS), with a prevalence of 6\u201315% of osteoporosis and of 25\u201348% of osteopenia. Reduced bone mass has been described since adolescence and it might be related to both reduced bone formation and higher bone resorption. Although reduced testosterone levels are clearly involved in the pathogenesis, this relation is not always evident. Importantly, fracture risk is increased independently from bone mineral density (BMD) and testosterone levels. Here we discuss the pathogenesis of osteoporosis in patients with KS, with a particular focus on the role of testosterone and testis function. In fact, other hormonal mechanisms, such as global Leydig cell dysfunction, causing reduced insulin-like factor 3 and 25-OH vitamin D levels, and high follicle-stimulating hormone and estradiol levels, might be involved. Furthermore, genetic aspects related to the supernumerary X chromosome might be involved, as well as androgen receptor expression and function. Notably, body composition, skeletal mass and strength, and age at diagnosis are other important aspects. Although dual-energy x-ray absorptiometry is recommended in the clinical workflow for patients with KS to measure BMD, recent evidence suggests that alterations in the microarchitecture of the bones and vertebral fractures might be present even in subjects with normal BMD. Therefore, analysis of trabecular bone score, high-resolution peripheral quantitative computed tomography and vertebral morphometry seem promising tools to better estimate the fracture risk of patients with KS. This review also summarizes the evidence on the best available treatments for osteoporosis in men with KS, with or without hypogonadism.<\/jats:p>","DOI":"10.1530\/ec-23-0058","type":"journal-article","created":{"date-parts":[[2023,5,11]],"date-time":"2023-05-11T10:10:04Z","timestamp":1683799804000},"update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-10","source":"Crossref","is-referenced-by-count":20,"title":["Osteoporosis and bone metabolism in patients with Klinefelter syndrome"],"prefix":"10.1530","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3264-0937","authenticated-orcid":true,"given":"Giuseppe","family":"Grande","sequence":"first","affiliation":[{"name":"Unit of Andrology and Reproductive Medicine, University Hospital of Padova, Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Graziani","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Padova, Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonella","family":"Di Mambro","sequence":"additional","affiliation":[{"name":"Unit of Andrology and Reproductive Medicine, University Hospital of Padova, Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riccardo","family":"Selice","sequence":"additional","affiliation":[{"name":"Unit of Andrology and Reproductive Medicine, University Hospital of Padova, Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5817-8141","authenticated-orcid":true,"given":"Alberto","family":"Ferlin","sequence":"additional","affiliation":[{"name":"Unit of Andrology and Reproductive Medicine, University Hospital of Padova, Padova, Italy"},{"name":"Department of Medicine, University of Padova, Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","reference":[{"key":"bib1","series-title":"Andrology","first-page":"145","article-title":"European academy of andrology guidelines on Klinefelter Syndrome Endorsing Organization: European Society of Endocrinology","volume":"9","author":"Zitzmann","year":"2021","unstructured":"Zitzmann MAksglaede LCorona GIsidori AMJuul AT\u2019Sjoen GKliesch SD\u2019Hauwers KToppari JS\u0142owikowska-Hilczer J, et al. 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