Clinical review 144: Estrogen and the male skeleton

Sundeep Khosla, L. Joseph Melton, B. Lawrence Riggs

Research output: Contribution to journalArticle

247 Citations (Scopus)

Abstract

Because estrogen (E) and T are the major sex steroids in women and men, respectively, the traditional view had been that E primarily regulated bone turnover in women and T played the analogous role in men. The description of ER-deficient and aromatase-deficient males, however, initiated a major shift in our thinking on the relative roles of T and E in regulating the male skeleton, because these individuals all had unfused epiphyses, high bone turnover, and osteopenia. Similar, albeit less striking, findings were noted in mouse models with knock-out of either the ER-α or the aromatase genes. Although these human experiments of nature and mouse knock-out models clearly demonstrated an important role for E in the growth and maturation of the male skeleton, they did not define the role of E vs. T in regulating the adult male skeleton. The past several years have witnessed an accumulation of evidence from observational as well as direct interventional studies that now clearly indicates that E plays a major, and likely dominant, role in bone metabolism in men. These data also suggest that a threshold level of bioavailable (or non-SHBG bound) E is needed for skeletal E sufficiency in the male, and that with aging, an increasing percentage of elderly men begin to fall below this level. It is this subset of men who may be at greatest risk for the development of age-related bone loss and osteoporosis. Moreover, these men may also be the ones most likely to respond favorably to treatment with selective E receptor modulators, or perhaps even to T replacement, because the skeletal effects of the latter may be mediated largely via aromatization to E.

Original languageEnglish (US)
Pages (from-to)1443-1450
Number of pages8
JournalJournal of Clinical Endocrinology and Metabolism
Volume87
Issue number4
DOIs
StatePublished - 2002

Fingerprint

Skeleton
Bone
Estrogens
Aromatase
Bone Remodeling
Osteoporosis
Aromatization
Set theory
Epiphyses
Metabolism
Modulators
Metabolic Bone Diseases
Knockout Mice
Genes
Aging of materials
Steroids
Bone and Bones
Growth
Experiments
Therapeutics

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology, Diabetes and Metabolism

Cite this

Clinical review 144 : Estrogen and the male skeleton. / Khosla, Sundeep; Joseph Melton, L.; Lawrence Riggs, B.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 87, No. 4, 2002, p. 1443-1450.

Research output: Contribution to journalArticle

Khosla, Sundeep ; Joseph Melton, L. ; Lawrence Riggs, B. / Clinical review 144 : Estrogen and the male skeleton. In: Journal of Clinical Endocrinology and Metabolism. 2002 ; Vol. 87, No. 4. pp. 1443-1450.
@article{8df143df173040ceb7dad4f1eae81539,
title = "Clinical review 144: Estrogen and the male skeleton",
abstract = "Because estrogen (E) and T are the major sex steroids in women and men, respectively, the traditional view had been that E primarily regulated bone turnover in women and T played the analogous role in men. The description of ER-deficient and aromatase-deficient males, however, initiated a major shift in our thinking on the relative roles of T and E in regulating the male skeleton, because these individuals all had unfused epiphyses, high bone turnover, and osteopenia. Similar, albeit less striking, findings were noted in mouse models with knock-out of either the ER-α or the aromatase genes. Although these human experiments of nature and mouse knock-out models clearly demonstrated an important role for E in the growth and maturation of the male skeleton, they did not define the role of E vs. T in regulating the adult male skeleton. The past several years have witnessed an accumulation of evidence from observational as well as direct interventional studies that now clearly indicates that E plays a major, and likely dominant, role in bone metabolism in men. These data also suggest that a threshold level of bioavailable (or non-SHBG bound) E is needed for skeletal E sufficiency in the male, and that with aging, an increasing percentage of elderly men begin to fall below this level. It is this subset of men who may be at greatest risk for the development of age-related bone loss and osteoporosis. Moreover, these men may also be the ones most likely to respond favorably to treatment with selective E receptor modulators, or perhaps even to T replacement, because the skeletal effects of the latter may be mediated largely via aromatization to E.",
author = "Sundeep Khosla and {Joseph Melton}, L. and {Lawrence Riggs}, B.",
year = "2002",
doi = "10.1210/jc.87.4.1443",
language = "English (US)",
volume = "87",
pages = "1443--1450",
journal = "Journal of Clinical Endocrinology and Metabolism",
issn = "0021-972X",
publisher = "The Endocrine Society",
number = "4",

}

TY - JOUR

T1 - Clinical review 144

T2 - Estrogen and the male skeleton

AU - Khosla, Sundeep

AU - Joseph Melton, L.

AU - Lawrence Riggs, B.

PY - 2002

Y1 - 2002

N2 - Because estrogen (E) and T are the major sex steroids in women and men, respectively, the traditional view had been that E primarily regulated bone turnover in women and T played the analogous role in men. The description of ER-deficient and aromatase-deficient males, however, initiated a major shift in our thinking on the relative roles of T and E in regulating the male skeleton, because these individuals all had unfused epiphyses, high bone turnover, and osteopenia. Similar, albeit less striking, findings were noted in mouse models with knock-out of either the ER-α or the aromatase genes. Although these human experiments of nature and mouse knock-out models clearly demonstrated an important role for E in the growth and maturation of the male skeleton, they did not define the role of E vs. T in regulating the adult male skeleton. The past several years have witnessed an accumulation of evidence from observational as well as direct interventional studies that now clearly indicates that E plays a major, and likely dominant, role in bone metabolism in men. These data also suggest that a threshold level of bioavailable (or non-SHBG bound) E is needed for skeletal E sufficiency in the male, and that with aging, an increasing percentage of elderly men begin to fall below this level. It is this subset of men who may be at greatest risk for the development of age-related bone loss and osteoporosis. Moreover, these men may also be the ones most likely to respond favorably to treatment with selective E receptor modulators, or perhaps even to T replacement, because the skeletal effects of the latter may be mediated largely via aromatization to E.

AB - Because estrogen (E) and T are the major sex steroids in women and men, respectively, the traditional view had been that E primarily regulated bone turnover in women and T played the analogous role in men. The description of ER-deficient and aromatase-deficient males, however, initiated a major shift in our thinking on the relative roles of T and E in regulating the male skeleton, because these individuals all had unfused epiphyses, high bone turnover, and osteopenia. Similar, albeit less striking, findings were noted in mouse models with knock-out of either the ER-α or the aromatase genes. Although these human experiments of nature and mouse knock-out models clearly demonstrated an important role for E in the growth and maturation of the male skeleton, they did not define the role of E vs. T in regulating the adult male skeleton. The past several years have witnessed an accumulation of evidence from observational as well as direct interventional studies that now clearly indicates that E plays a major, and likely dominant, role in bone metabolism in men. These data also suggest that a threshold level of bioavailable (or non-SHBG bound) E is needed for skeletal E sufficiency in the male, and that with aging, an increasing percentage of elderly men begin to fall below this level. It is this subset of men who may be at greatest risk for the development of age-related bone loss and osteoporosis. Moreover, these men may also be the ones most likely to respond favorably to treatment with selective E receptor modulators, or perhaps even to T replacement, because the skeletal effects of the latter may be mediated largely via aromatization to E.

UR - http://www.scopus.com/inward/record.url?scp=0036283611&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0036283611&partnerID=8YFLogxK

U2 - 10.1210/jc.87.4.1443

DO - 10.1210/jc.87.4.1443

M3 - Article

C2 - 11932262

AN - SCOPUS:0036283611

VL - 87

SP - 1443

EP - 1450

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

SN - 0021-972X

IS - 4

ER -