Sex steroids and bone health in men

Journal article


Ohlsson, Claes, Börjesson, Anna E. and Vandenput, Liesbeth. (2012). Sex steroids and bone health in men. BoneKEy Reports. 1(2), pp. 1 - 7. https://doi.org/10.1038/bonekey.2012.3
AuthorsOhlsson, Claes, Börjesson, Anna E. and Vandenput, Liesbeth
Abstract

The influence of sex steroids on bone in both men and women has long been recognized. In men, however, the relative contribution of androgens versus estrogens in the regulation of bone metabolism remains uncertain. Animal studies demonstrate that both estradiol (E2), via activation of estrogen receptor- , and testosterone (T), via activation of the androgen receptor, regulate bone mass in male rodents. The main focus of this review is to summarize and discuss recent findings from the osteoporotic fractures in men (MrOS) cohorts regarding the impact of serum sex steroids on bone health in elderly men. Collectively, these data demonstrate that serum E2 is directly associated with bone mineral density (BMD) and that low serum E2 associates with higher rates of bone loss and fracture. In addition, they substantiate the concept of a threshold E2 level that determines fracture risk in elderly men. We propose that the effect of E2 on fracture risk is at least partly mediated by its effect on BMD, whereas the more modest effect of T on fracture risk mainly is mediated by effects on muscle strength and risk of falls. Findings from the MrOS cohorts also demonstrate that racial and genetic variations in aromatase activity influence serum E2 levels in men. In conclusion, there is compelling evidence that not only androgens, but also estrogens, are important regulators of bone health in men. Consequently, E2 should not exclusively be regarded as the ‘ female hormone ’but as a sex steroid that is necessary for maintenance of bone health in men.

Year2012
JournalBoneKEy Reports
Journal citation1 (2), pp. 1 - 7
PublisherInternational Bone and Mineral Society
ISSN2047-6396
Digital Object Identifier (DOI)https://doi.org/10.1038/bonekey.2012.3
Page range1 - 7
Research GroupMary MacKillop Institute for Health Research
Publisher's version
File Access Level
Controlled
Place of publicationUnited States of America
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Serum DHEA and Its Sulfate Are Associated With Incident Fall Risk in Older Men: The MrOS Sweden study
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Genetic determinants of circulating estrogen levels and evidence of a causal effect of estradiol on bone density in men
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The limited clinical utility of testosterone, estradiol, and sex hormone binding globulin measurements in the prediction of fracture risk and bone loss in older men
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Large meta-analysis of genome-wide association studies identifies five loci for lean body mass
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Umbilical cord blood androgen levels in girls and boys assessed by gas chromatography-tandem mass spectrometry
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Increased adipose tissue aromatase activity improves insulin sensitivity and reduces adipose tissue inflammation in male mice
Ohlsson, Claes, Hammarstedt, Ann, Vandenput, Liesbeth, Saarinen, Niina, Ryberg, Henrik, Windahl, Sara H., Farman, Helen H., Jansson, John-Olov, Movérare-Skrtic, Sofia, Smith, Ulf, Zhang, Fu-Ping, Poutanen, Matti, Hedjazifar, Shahram and Sjögren, Klara. (2017). Increased adipose tissue aromatase activity improves insulin sensitivity and reduces adipose tissue inflammation in male mice. American Journal of Physiology - Endocrinology and Metabolism. 313(4), pp. E450 - E462. https://doi.org/10.1152/ajpendo.00093.2017
Low testosterone, but not estradiol, is associated with incident falls in older men: The international MrOS study
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Low-frequency synonymous coding variation in CYP2R1 has large effects on vitamin d levels and risk of multiple sclerosis
Manousaki, Despoina, Dudding, Tom, Haworth, Simon, Hsu, Yi-Hsiang, Liu, Chiang-Ti, Medina-Gómez, Carolina, Voortman, Trudy, van der Velde, Nathalie, Melhus, Håkan, Robinson-Cohen, Cassianne, Cousminer, Diana L., Nethander, Maria, Vandenput, Liesbeth, Noordam, Raymond, Forgetta, Vincenzo, Greenwood, Celia M. T., Biggs, Mary L., Psaty, Bruce M., Rotter, Jerome I., ... Richards, J. Brent. (2017). Low-frequency synonymous coding variation in CYP2R1 has large effects on vitamin d levels and risk of multiple sclerosis. American Journal of Human Genetics. 101(2), pp. 227 - 238. https://doi.org/10.1016/j.ajhg.2017.06.014
Causal relationship between obesity and serum testosterone status in men: A bi-directional mendelian randomization analysis
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Low serum DHEAS predicts increased fracture risk in older men: The MrOS Sweden study
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New loci for body fat percentage reveal link between adiposity and cardiometabolic disease risk
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A principal component meta-analysis on multiple anthropometric traits identifies novel loci for body shape
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High serum SHBG predicts incident vertebral fractures in elderly men
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The Influence of Age and Sex on Genetic Associations with Adult Body Size and Shape : A Large-Scale Genome-Wide Interaction Study
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Genetic studies of body mass index yield new insights for obesity biology
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Hydroxysteroid (17 beta)-dehydrogenase 1–deficient female mice present with normal puberty onset but are severely subfertile due to a defect in luteinization and progesterone production
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Measurement of a comprehensive sex steroid profile in rodent serum by high-sensitive gas chromatography-tandem mass spectrometry
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Sleep duration and disturbances were associated with testosterone level, muscle mass, and muscle strength - A cross-sectional study in 1274 older men
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Limited clinical utility of a genetic risk score for the prediction of fracture risk in elderly subjects
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Sex steroid actions in male bone
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Genome-wide association study for radiographic vertebral fractures: A potential role for the 16q24 BMD locus
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Serum estradiol levels are inversely associated with cortical porosity in older men
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Serum estradiol associates with blood hemoglobin in elderly men: The MrOS Sweden study
Lewerin, Catharina, Nilsson-Ehle, Herman, Jacobsson, Stefan, Johansson, Helena, Sundh, Valter, Karlsson, Magnus K., Lorentzon, Mattias, Barrett-Connor, Elizabeth, Vandenput, Liesbeth, Ohlsson, Claes and Mellström, Dan. (2014). Serum estradiol associates with blood hemoglobin in elderly men: The MrOS Sweden study. The Journal of Clinical Endocrinology and Metabolism. 99(7), pp. 2549 - 2556. https://doi.org/10.1210/jc.2013-4111
Genome-wide association studies on serum sex steroid levels
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Does bone resorption stimulate periosteal expansion? A cross-sectional analysis of β-C-telopeptides of type i collagen (CTX), genetic markers of the RANKL pathway, and periosteal circumference as measured by pQCT
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Dehydroepiandrosterone and its sulfate predict the 5-year risk of coronary heart disease events in elderly men
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Genetics of endocrine disorders in the era of genome-wide association studies
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Meta-analysis of genome-wide association studies identifies two loci associated with circulating osteoprotegerin levels
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Causal relationship between obesity and vitamin d status : Bi-directional mendelian randomization analysis of multiple cohorts
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Genetic determinants of trabecular and cortical volumetric bone mineral densities and bone microstructure
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Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture
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Comparisons of immunoassay and mass spectrometry measurements of serum estradiol levels and their influence on clinical association studies in men
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Assessment of gene-by-sex interaction effect on bone mineral density
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A genome-wide association meta-analysis of circulating sex hormone-binding globulin reveals multiple loci implicated in sex steroid hormone regulation
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Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture
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WNT16 influences bone mineral density, cortical bone thickness, bone strength, and osteoporotic fracture risk
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The role of IGF-1 for fracture risk in men
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Sex steroids and bone health in older Chinese men
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Meta-analysis of genome-wide scans for total body BMD in children and adults reveals allelic heterogeneity and age-specific effects at the WNT16 locus
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Genetic variation near IRS1 associates with reduced adiposity and an impaired metabolic profile
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Eight common genetic variants associated with serum DHEAS levels suggest a key role in ageing mechanisms
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Low DHEAS levels are associated with depressive symptoms in elderly Chinese men: results from a large study
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