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We aimed to investigate the total OCN (tOCN) concentrations in male patients with Klinefelter syndrome (KS), a model of adult hypergonadotropic hypogonadism.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>This retrospective longitudinal study investigated 254 male patients with KS (47,XXY) between 2007 and 2021 at an academic referral center, categorized as (1) prepubertal, (2) pubertal, and (3) adults. All prepubertal patients were Te-na\u00efve. Adult patients were subcategorized as (1) eugonadal, (2) hypogonadal, and (3) receiving TRT. We also analyzed 18 adult patients with\u00a0available tOCN levels before and 3\u00a0months after TRT commencement.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>The tOCN levels varied throughout the lifespan according to pubertal status, were highest in eugonadal and significantly lower in TRT subjects, correlated with both LH (<jats:italic>p<\/jats:italic>\u2009=\u20090.017) and FSH levels (<jats:italic>p<\/jats:italic>\u2009=\u20090.004) in adults, and significantly declined after 3\u00a0months of TRT (<jats:italic>p<\/jats:italic>\u2009=\u20090.006) in the adult KS cohort. HPG-axis hormones levels demonstrated no correlation in prepubertal boys. Adjustment for age and body mass index confirmed previous results and revealed significant inverse correlations with total Te (<jats:italic>p<\/jats:italic>\u2009=\u20090.004), calculated free Te (<jats:italic>p<\/jats:italic>\u2009=\u20090.016), the Te\/LH (<jats:italic>p<\/jats:italic>\u2009=\u20090.010), and calculated free Te\/LH ratios (<jats:italic>p<\/jats:italic>\u2009=\u20090.031).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>In KS, a model of male hypergonadotropic hypogonadism, tOCN levels were not associated with gonadal function during normal prepuberty and pubertal development but were associated with worse testicular function and a higher degree of HPG stimulation in adults. TRT acutely\u00a0reduced tOCN levels in adults.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s40618-024-02390-7","type":"journal-article","created":{"date-parts":[[2024,5,21]],"date-time":"2024-05-21T17:01:52Z","timestamp":1716310912000},"page":"3049-3056","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Total osteocalcin levels are independently associated with worse testicular function and a higher degree of hypothalamic\u2013pituitary\u2013gonadal axis activation in Klinefelter syndrome"],"prefix":"10.1007","volume":"47","author":[{"given":"F.","family":"Carlomagno","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V.","family":"Hasenmajer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Spaziani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Tenuta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F.","family":"Sesti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Tarantino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Pozza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. 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