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Osteoporosis in Klinefelter Syndrome

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Male Osteoporosis

Part of the book series: Trends in Andrology and Sexual Medicine ((TASM))

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Abstract

Osteoporosis is present in up to 40% of subjects with Klinefelter syndrome and has usually been attributed to low testosterone levels. Hypogonadism represents one of the most important causes of male osteoporosis. Testosterone regulates male bone metabolism both indirectly by aromatization to estrogens and directly through the androgen receptor on osteoblasts, promoting periosteal bone formation during puberty and reducing bone resorption during adult life. Early onset of testosterone deficiency, as observed in KS, is an important risk factor for precocious osteoporosis. However, reduced bone mass might be present also in KS men with normal testosterone levels, and testosterone replacement therapy does not always restore bone density in KS patients. Possible new determinants for osteoporosis in KS might be related to the AR function, insulin-like factor 3 (INSL3), and 25-hydroxyvitamin D levels. The CAG length and inactivation pattern of the AR in KS have been related to osteoporosis, but definitive proof is lacking. INSL3 has an anabolic role on bone metabolism by acting on osteoblasts, and INSL3 levels are low in KS. Therefore, low INSL3 concentrations might represent a possible new pathogenic mechanism for reduced bone mass in KS. Recent studies suggest that low 25-hydroxyvitamin D levels have a more critical role than low T levels in inducing low BMD in KS subjects and that vitamin D supplementation seems to be more effective than T replacement therapy alone in increasing BMD.

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Authors and Affiliations

  1. Department of Medicine and Centre for Human Reproductive Pathology, University of Padova, Padova, Italy

    Riccardo Selice

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  1. Riccardo Selice
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Editors and Affiliations

  1. Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy

    Alberto Ferlin

  2. Department of Movement Human and Health Sciences, Foro Italico University of Rome, Rome, Italy

    Silvia Migliaccio

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Selice, R. (2020). Osteoporosis in Klinefelter Syndrome. In: Ferlin, A., Migliaccio, S. (eds) Male Osteoporosis. Trends in Andrology and Sexual Medicine. Springer, Cham. https://doi.org/10.1007/978-3-319-96376-1_9

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  • DOI: https://doi.org/10.1007/978-3-319-96376-1_9

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