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Cited by 860Bone health and osteoporosis researchEstrogen and related hormone effectsBone Metabolism and Diseases

Estrogens and androgens in skeletal physiology and pathophysiology

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Almeida, Maria, Laurent, Michaël R., Dubois, Vanessa, Claessens, Frank, O'Brien, Charles A., Bouillon, Roger, Vanderschueren, Dirk, Manolagas, Stavros C.·2017·Physiological Reviews
DOI 10.1152/physrev.00033.2015PMC PMC5539371
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Abstract

Estrogens and androgens influence the growth and maintenance of the mammalian skeleton and are responsible for its sexual dimorphism. Estrogen deficiency at menopause or loss of both estrogens and androgens in elderly men contribute to the development of osteoporosis, one of the most common and impactful metabolic diseases of old age. In the last 20 years, basic and clinical research advances, genetic insights from humans and rodents, and newer imaging technologies have changed considerably the landscape of our understanding of bone biology as well as the relationship between sex steroids and the physiology and pathophysiology of bone metabolism. Together with the appreciation of the side effects of estrogen-related therapies on breast cancer and cardiovascular diseases, these advances have also drastically altered the treatment of osteoporosis. In this article, we provide a comprehensive review of the molecular and cellular mechanisms of action of estrogens and androgens on bone, their influences on skeletal homeostasis during growth and adulthood, the pathogenetic mechanisms of the adverse effects of their deficiency on the female and male skeleton, as well as the role of natural and synthetic estrogenic or androgenic compounds in the pharmacotherapy of osteoporosis. We highlight latest advances on the crosstalk between hormonal and mechanical signals, the relevance of the antioxidant properties of estrogens and androgens, the difference of their cellular targets in different bone envelopes, the role of estrogen deficiency in male osteoporosis, and the contribution of estrogen or androgen deficiency to the monomorphic effects of aging on skeletal involution.

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Crossref · 10.1152/physrev.00033.2015

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  • Androgen effects on bone are mediated by both direct effects on the androgen receptor and indirect effects via aromatization of testosterone to estradiol acting on estrogen receptors.

    “These effects have been reported from studies of global and tissue or cell-selective inactivation of ARs or estrogen receptors that show that androgen effects are mediated by both direct effects on the AR as well as indirect effects mediated via aromatization of testosterone to estradiol to act on estrogen receptors [reviewed in (135)].”

    From Circulating Testosterone as the Hormonal Basis of Sex Differences in Athletic Performance (2018) · cites this paper as [135]

  • Extensive experimental evidence from genetic mouse models shows that sex differences in bone size, mass, and function are due to the sex difference in circulating testosterone.

    “There is extensive experimental evidence from genetic mouse models showing that the sex differences in bone size, mass, and function are due to the sex difference in circulating testosterone.”

    From Circulating Testosterone as the Hormonal Basis of Sex Differences in Athletic Performance (2018) · cites this paper as [135]

  • Sex differences in bone are absent prior to puberty but accrue progressively from the onset of male puberty due to the sex difference in exposure to adult male circulating testosterone concentrations.

    “As with muscle, sex differences in bone are absent prior to puberty but then accrue progressively from the onset of male puberty due to the sex difference in exposure to adult male circulating testosterone concentrations [reviewed in (135)].”

    From Circulating Testosterone as the Hormonal Basis of Sex Differences in Athletic Performance (2018) · cites this paper as [135]

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Research works printed but not linked: 12

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Authors
Almeida, M., Laurent, M. R., Dubois, V., Claessens, F., O'Brien, C. A., Bouillon, R., Vanderschueren, D., & Manolagas, S. C.
Affiliations
  • Inserm (FR)
  • Division of Endocrinology and Metabolism, Center for Osteoporosis and Metabolic Bone Diseases, University of Arkansas for Medical Sciences and the Central Arkansas Veterans Healthcare System, Little Rock, Arkansas; Departments of Cellular and Molecular Medicine and Clinical and Experimental Medicine, KU Leuven, Leuven, Belgium; Center for Metabolic Bone Diseases, University Hospitals Leuven, Leuven, Belgium; and Institut National de la Santé et de la Recherche Médicale UMR1011, University of Lille and...
ORCID
Venue
Physiological Reviews
Publisher
American Physiological Society
Published
2017-01
Volume
97
Issue
1
Pages
135-187
ISSN
  • 0031-9333 (ISSN-L)
  • 1522-1210
DOI
10.1152/physrev.00033.2015
PMC
PMC5539371
OpenAlex
W2547082780
Cited by
860
References
590
Citations by year
2026: 73 · 2025: 124 · 2024: 107 · 2023: 103 · 2022: 111 · 2021: 81 · 2020: 110 · 2019: 75 · 2018: 46 · 2017: 25 · 2016: 2 · 2015: 1
FWCI
7.84
Type
journal article
Language
en
Open access
Locations
  • Physiological Reviews (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • Ghent University Academic Bibliography (Ghent University) (submittedVersion)
  • Lirias (submittedVersion)
Funders
  • HHS | National Institutes of Health (NIH) (P01 AG13918, R01 AR56679, R01 AR049794)
  • Biomedical Laboratory Research and Development, VA Office of Research and Development (Biomedical Laboratory Research and Development Service of the VA Office of Research and Development) (I01 BX001405, 1I01BX000294)
  • University of Arkansas for Medical Sciences Tobacco Funds and Translational Research Institute (1UL1RR029884)
  • Research Foundation Flanders (G.0854.13N)
  • KU Leuven (Katholieke Universiteit Leuven) (G.0858.11, GOA/15/017)
Topics
  • Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
Keywords
estrogen, androgens, sex steroids, bone metabolism, osteoporosis, skeletal homeostasis, sexual dimorphism, menopause, male osteoporosis, aging, estrogen deficiency, estrogen receptor, androgen receptor, osteoporosis pharmacotherapy, bone growth
MeSH terms
Androgens, Animals, Bone and Bones, Estrogens, Female, Homeostasis, Humans, Male, Osteoporosis

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