Estrogens and Androgens in Skeletal Physiology and Pathophysiology.
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.
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 Institut Pasteur de Lille, Lille, France.
Maria
M
Almeida
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 Institut Pasteur de Lille, Lille, France.
Michaël R
MR
Laurent
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 Institut Pasteur de Lille, Lille, France.
Vanessa
V
Dubois
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 Institut Pasteur de Lille, Lille, France.
Frank
F
Claessens
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 Institut Pasteur de Lille, Lille, France.
Charles A
CA
O'Brien
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 Institut Pasteur de Lille, Lille, France.
Roger
R
Bouillon
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 Institut Pasteur de Lille, Lille, France.
Dirk
D
Vanderschueren
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 Institut Pasteur de Lille, Lille, France.
Stavros C
0000-0001-9681-8330
SC
Manolagas
D000728:Androgens / Q000378:metabolism*; D000818:Animals; D001842:Bone and Bones / Q000378:metabolism* / Q000503:physiopathology*; D004967:Estrogens / Q000378:metabolism*; D005260:Female; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D008297:Male; D010024:Osteoporosis / Q000378:metabolism / Q000503:physiopathology*
D000728:Androgens; D004967:Estrogens