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Testicular function and bone metabolism—beyond testosterone

Nature Reviews Endocrinology volume 9, pages 548–554 (2013)Cite this article

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Abstract

Findings in the past few years have advanced understanding of the crosstalk between testis and bone and could contribute to defining an improved clinical approach to the biochemical diagnosis and therapeutic management of hypogonadism and male osteoporosis. This Review focuses on the Leydig cells of the testis. Other than being responsible for steroidogenesis and production of testosterone, the function of these cells is fundamental to bone health in at least two other ways: Leydig cells produce insulin-like 3 (INSL3), which has a role in osteoblast function, and they contribute to 25-hydroxylation of vitamin D. Impairment of testicular function leads to low levels of testosterone, INSL3 and 25-hydroxyvitamin D and consequently to an increased risk of osteopenia and osteoporosis.

Key Points

  • Hypogonadism is a common secondary cause of male osteoporosis; however, men with mild testicular dysfunction are also at increased risk of osteopenia and osteoporosis

  • Knowledge of the bidirectional crosstalk between testis and bone obtained in the past few years could inform the clinical approach to the diagnosis and therapeutic management of hypogonadism and male osteoporosis

  • The testis might also contribute to bone health in a testosterone-independent manner by production of insulin-like 3 (INSL3) and by contributing to the 25-hydroxylation of vitamin D

  • INSL3 and 25-hydroxyvitamin D are sensitive markers of Leydig cell function in subclinical hypogonadism, when their levels are reduced and might contribute to low bone mass despite normal testosterone levels

  • Testosterone replacement therapy alone in men with hypogonadism does not completely restore bone mass, which suggests that alternative therapeutic approaches should be considered in future studies

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Figure 1: Schematic representation of the crosstalk between testis and bone.

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Authors and Affiliations

  1. Department of Molecular Medicine, Section of Clinical Pathology & Center for Human Reproduction Pathology, University of Padova, Via Gabelli 63, 35121, Padova, Italy

    Alberto Ferlin, Riccardo Selice, Umberto Carraro & Carlo Foresta

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  1. Alberto Ferlin
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Contributions

A. Ferlin, R. Selice and U. Carraro researched data for the article, provided a substantial contribution to a discussion of the content, wrote the article, and reviewed and/or edited the manuscript before submission. C. Foresta provided a substantial contribution to a discussion of the content and reviewed and/or edited the manuscript before submission.

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Correspondence to Alberto Ferlin.

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Ferlin, A., Selice, R., Carraro, U. et al. Testicular function and bone metabolism—beyond testosterone. Nat Rev Endocrinol 9, 548–554 (2013). https://doi.org/10.1038/nrendo.2013.135

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