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Sex steroids and bone mass in older men. Positive associations with serum estrogens and negative associations with androgens.
Open accessAbstract
The purpose of this study was to determine whether bone density in older men was associated with serum sex steroids or sex hormone binding globulin (SHBG). Bone density and sex steroids were measured in men over age 65 at 6-mo intervals for an average of 2.1 yr. Bone density was significantly positively associated with greater serum E2 concentrations (+0.21 < r < +0.35; 0.01 < P < 0.05) at all skeletal sites. There were weak negative correlations between serum testosterone and bone density (-0.20 < r < -0.28; 0.03 < P < 0.10) at the spine and hip. SHBG was negatively associated only with bone density in the greater trochanter (r = -0.26, P < 0.05). Greater body weight was associated with lower serum testosterone and SHBG, and greater E2. Because of these associations, regression models which adjusted for age, body weight, and serum sex steroids were constructed; these accounted for 10-30% of the variability in bone density, and showed consistent, significant positive associations between bone density and serum E2 concentrations in men, even after adjustments for weight and SHBG. These data suggest that estrogens may play an important role in the development or maintenance of the male skeleton, much as is the case for the female skeleton. These data also indicate that, within the normal range, lower serum testosterone concentrations are not associated with low bone density in men.
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“Moreover, in men, bone mineral density (BMD) at the greater trochanter, femoral neck and the lumbar spine is negatively correlated with concentrations of SHBG [146, 150–152].”
From Role of sex hormone-binding globulin in the free hormone hypothesis and the relevance of free testosterone in androgen physiology (2022) · cites this paper as [151]
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“These confounding results leave uncertainty in the relationship between T levels in aging and bone health.”
From Hormonal and Metabolic Changes of Aging and the Influence of Lifestyle Modifications (2021) · cites this paper as [175]
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“However, Slemenda and colleagues (41) found that BMD (assessed by DXA) at various sites in 93 healthy men over age 55 years correlated with serum estradiol levels (correlation coefficients, depending on the site, of +0.”
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“In older men, serum estradiol levels are positively associated with spinal BMD and negatively associated with vertebral fracture risk”
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The osteoporotic male: overlooked and undermanaged?
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Osteoporosis in Men: Update 2011
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“There is inconsistent evidence for role of testosterone in the maintenance of BMD in men (158, 382), although some studies found a direct association between decreasing testosterone levels and lower BMD (32, 134) and testosterone clinically improves trabecular BMD in the spine (385) Some of these…”
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The Role of Sex Steroids in the Pathogenesis of Osteoporosis
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Oestrogen, bones and men: when testosterone just isn't enough
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“Second, was oestrogen necessary for the maintenance of bone mass in adult men? Finally, what, if any, was the role of oestrogen (or possible oestrogen deficiency) in mediating age-related bone loss in men? To try to answer some of these questions, a number of crosssectional observational studies related bone mineral d…”
BackgroundPrevención y tratamiento de la osteoporosis
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“Estrogen plays an important role in regulating bone resorption (Riggs, 2000) and has been associated with greater bone density in men and women (Khosla et al., 1998; Slemenda et al., 1997).”
BackgroundGenetic and Constitutional Influences on Bone Turnover Markers: A Study of Male Twin Pairs
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“, hypogonadism, thyroid/ parathyroid dysfunction, recent fracture and prolonged bed rest, which is thought to contribute to marker level increases up to 50% [7]) were excluded.”
BackgroundLoures, M. A. A. D. R., Zerbini, C. A. F., Danowski, J. S., Pereira, R. M. R., Moreira, C., de Paula, A. P., Castro, C. H. D. M., Szejnfeld, V. L., de Mendonça, L. M. C., Radominiski, S. C., et al. (2017) · Revista Brasileira de Reumatologia · doi:10.1016/j.rbr.2017.06.002 · Cited by 15
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InfluentialEstrogen Effects on Bone in the Male Skeleton
Bilezikian, J. P., Khosla, S., & Riggs, B. L. (2002) · Elsevier eBooks · doi:10.1016/b978-012098652-1.50187-6 · Cited by 16
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Metadata
- Authors
- Slemenda, C. W., Longcope, C., Zhou, L., Hui, S. L., Peacock, M., & Johnston, C. C.
- Affiliations
- Indiana University Indianapolis (US)
- University of Massachusetts Chan Medical School (US)
- Indiana University School of Medicine (US)
- Indiana University Bloomington (US)
- ORCID
- Venue
- Journal of Clinical Investigation
- Published
- 1997-10-01
- Volume
- 100
- Issue
- 7
- Pages
- 1755-1759
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC508359
- OpenAlex
- W1993231839
- Cited by
- 455
- References
- 28
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 2 · 2023: 6 · 2022: 8 · 2021: 7 · 2020: 7 · 2019: 9 · 2018: 7 · 2017: 6 · 2016: 8 · 2015: 8 · 2014: 6 · 2013: 7 · 2012: 16
- FWCI
- 24.09
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5p01ag005793-15)
- National Institute on Aging (P01-AG-05793)
- National Center for Research Resources (M01RR000750)
- Topics
- Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Endocrinology › Estrogen and related hormone effects
- Keywords
- sex steroids, bone mineral density, older men, serum estrogen, estradiol, testosterone, sex hormone-binding globulin, bone mass, body weight, male skeleton
- MeSH terms
- Aged, Androgens, Body Constitution, Dehydroepiandrosterone, Estradiol, Estrogens, Estrone, Humans, Longitudinal Studies, Male, Middle Aged, Prospective Studies, Regression Analysis, Sex Hormone-Binding Globulin, Testosterone, Models, Statistical, Bone Density, Dehydroepiandrosterone Sulfate
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