Cited by 455Bone health and osteoporosis researchHormonal and reproductive studiesEstrogen and related hormone effects

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Sex steroids and bone mass in older men. Positive associations with serum estrogens and negative associations with androgens.

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Slemenda, C W, Longcope, C, Zhou, L, Hui, S L, Peacock, M, Johnston, C C·1997·Journal of Clinical Investigation

DOI 10.1172/jci119701PMC PMC508359

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Abstract

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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Estrogens as regulators of bone health in men
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Osteoporosis in Men
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Predictors of low bone mineral density in the elderly: the role of dietary intake, nutritional status and sarcopenia
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“This association has been explained on the strength of biomechanical forces (Glynn et al., 1995) and a greater aromatization of androgens at subcutaneous adipose tissue level (Rebuffe-Scrive et al., 1990; Murphy et al., 1993; Vaananen and Harkonen, 1996; Slemenda et al., 1997).”
Toremifene Increases Bone Mineral Density in Men Receiving Androgen Deprivation Therapy for Prostate Cancer: Interim Analysis of a Multicenter Phase 3 Clinical Study
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Background
Lasofoxifene (CP-336,156), a Selective Estrogen Receptor Modulator, Prevents Bone Loss Induced by Aging and Orchidectomy in the Adult Rat
Ke, H. Z., Qi, H., Crawford, D. T., Chidsey-Frink, K. L., Simmons, H. A., & Thompson, D. D. (2000) · Endocrinology · doi:10.1210/endo.141.4.7408 · Cited by 116
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The Effect of Aromatase Inhibition on Sex Steroids, Gonadotropins, and Markers of Bone Turnover in Older Men
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Genetics of Osteoporosis
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Osteoporosis and male age-related hypogonadism: role of sex steroids on bone (patho)physiology
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Andropause: is androgen replacement therapy indicated for the aging male?
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Osteoporosis in hemodialysis patients revisited by bone histomorphometry: A new insight into an old problem
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Narinx, N., David, K., Walravens, J., Vermeersch, P., Claessens, F., Fiers, T., Lapauw, B., Antonio, L., & Vanderschueren, D. (2022) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-022-04562-1 · Cited by 96
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“[79] There were also negative associ-”
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Pottelbergh, I. V., Lumbroso, S., Goemaere, S., Sultan, C., & Kaufman, J. (2001) · Clinical Endocrinology · doi:10.1046/j.1365-2265.2001.01403.x · Cited by 95
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Estrogens and Bone Health in Men
Khosla, S., Melton, L. J., & Riggs, B. L. (2001) · Calcified Tissue International · doi:10.1007/s00223-001-1044-8 · Cited by 72
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Background
Estrogen deposits extra mineral into bones of female rats in puberty, but simultaneously seems to suppress the responsiveness of female skeleton to mechanical loading
Järvinen, T. L. N., Kannus, P., Pajamäki, I., Vuohelainen, T., Tuukkanen, J., Järvinen, M., & Sievänen, H. T. (2003) · Bone · doi:10.1016/s8756-3282(03)00100-5 · Cited by 97
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Background
NEUROENDOCRINE AGING IN MEN
Anawalt, B. D., & Merriam, G. R. (2001) · Endocrinology and Metabolism Clinics of North America · doi:10.1016/s0889-8529(05)70206-1 · Cited by 93
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Background
Estrogen receptor alpha, but not estrogen receptor beta, is involved in the regulation of the OPG/RANKL (osteoprotegerin/receptor activator of NF-kappa B ligand) ratio and serum interleukin-6 in male mice
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Growth Hormone and Sex Steroid Effects on Bone Metabolism and Bone Mineral Density in Healthy Aged Women and Men
Christmas, C., O'Connor, K. G., Harman, S. M., Tobin, J. D., Münzer, T., Bellantoni, M. F., Clair, C. S., Pabst, K. M., Sorkin, J. D., & Blackman, M. R. (2002) · The Journals of Gerontology Series A · doi:10.1093/gerona/57.1.m12 · Cited by 90
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Background
Body composition characteristics are associated with the bone density of the proximal femur end in middle- and old-aged women and men
Kirchengast, S., Peterson, B., Hauser, G., & Knogler, W. (2001) · Maturitas · doi:10.1016/s0378-5122(01)00205-5 · Cited by 83
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Lasofoxifene (CP-336,156) Protects Against the Age-Related Changes in Bone Mass, Bone Strength, and Total Serum Cholesterol in Intact Aged Male Rats
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Testosterone Prevents Orchidectomy-Induced Bone Loss in Estrogen Receptor-α Knockout Mice
Vandenput, L., EDERVEEN, A. G. H., Erben, R. G., Stähr, K., Swinnen, J. V., Herck, E. V., Verstuyf, A., Boonen, S., Bouillon, R., & Vanderschueren, D. (2001) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.2001.5101 · Cited by 80

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: Zhou, L
Peacock, M
Venue: Journal of Clinical Investigation
Publisher: American Society for Clinical Investigation
Published: 1997-10-01
Volume: 100
Issue: 7
Pages: 1755-1759
ISSN: 0021-9738 (ISSN-L)
DOI: 10.1172/jci119701
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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Sex steroids and bone mass in older men. Positive associations with serum estrogens and negative associations with androgens.

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