Critical Role of Estrogens on Bone Homeostasis in Both Male and Female: From Physiology to Medical Implications

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Abstract

Bone is a multi-skilled tissue, protecting major organs, regulating calcium phosphate balance and producing hormones. Its development during childhood determines height and stature as well as resistance against fracture in advanced age. Estrogens are key regulators of bone turnover in both females and males. These hormones play a major role in longitudinal and width growth throughout puberty as well as in the regulation of bone turnover. In women, estrogen deficiency is one of the major causes of postmenopausal osteoporosis. In this review, we will summarize the main clinical and experimental studies reporting the effects of estrogens not only in females but also in males, during different life stages. Effects of estrogens on bone involve either Estrogen Receptor (ER)α or ERβ depending on the type of bone (femur, vertebrae, tibia, mandible), the compartment (trabecular or cortical), cell types involved (osteoclasts, osteoblasts and osteocytes) and sex. Finally, we will discuss new ongoing strategies to increase the benefit/risk ratio of the hormonal treatment of menopause.

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European guidance for the diagnosis and management of osteoporosis in postmenopausal women

J.A. Kanis, C. Cooper, R Rizzoli … (2018)

Summary Guidance is provided in a European setting on the assessment and treatment of postmenopausal women at risk from fractures due to osteoporosis. Introduction The International Osteoporosis Foundation and European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis published guidance for the diagnosis and management of osteoporosis in 2013. This manuscript updates these in a European setting. Methods Systematic reviews were updated. Results The following areas are reviewed: the role of bone mineral density measurement for the diagnosis of osteoporosis and assessment of fracture risk; general and pharmacological management of osteoporosis; monitoring of treatment; assessment of fracture risk; case-finding strategies; investigation of patients; health economics of treatment. The update includes new information on the evaluation of bone microstructure evaluation in facture risk assessment, the role of FRAX® and Fracture Liaison Services in secondary fracture prevention, long-term effects on fracture risk of dietary intakes, and increased fracture risk on stopping drug treatment. Conclusions A platform is provided on which specific guidelines can be developed for national use.

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From estrogen-centric to aging and oxidative stress: a revised perspective of the pathogenesis of osteoporosis.

Stavros C. Manolagas (2010)

Estrogen deficiency has been considered the seminal mechanism of osteoporosis in both women and men, but epidemiological evidence in humans and recent mechanistic studies in rodents indicate that aging and the associated increase in reactive oxygen species (ROS) are the proximal culprits. ROS greatly influence the generation and survival of osteoclasts, osteoblasts, and osteocytes. Moreover, oxidative defense by the FoxO transcription factors is indispensable for skeletal homeostasis at any age. Loss of estrogens or androgens decreases defense against oxidative stress in bone, and this accounts for the increased bone resorption associated with the acute loss of these hormones. ROS-activated FoxOs in early mesenchymal progenitors also divert ss-catenin away from Wnt signaling, leading to decreased osteoblastogenesis. This latter mechanism may be implicated in the pathogenesis of type 1 and 2 diabetes and ROS-mediated adverse effects of diabetes on bone formation. Attenuation of Wnt signaling by the activation of peroxisome proliferator-activated receptor gamma by ligands generated from lipid oxidation also contributes to the age-dependent decrease in bone formation, suggesting a mechanistic explanation for the link between atherosclerosis and osteoporosis. Additionally, increased glucocorticoid production and sensitivity with advancing age decrease skeletal hydration and thereby increase skeletal fragility by attenuating the volume of the bone vasculature and interstitial fluid. This emerging evidence provides a paradigm shift from the "estrogen-centric" account of the pathogenesis of involutional osteoporosis to one in which age-related mechanisms intrinsic to bone and oxidative stress are protagonists and age-related changes in other organs and tissues, such as ovaries, accentuate them.

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Biology of Bone Tissue: Structure, Function, and Factors That Influence Bone Cells

Rinaldo Florencio-Silva, Gisela Sasso, Estela Sasso-Cerri … (2015)

Bone tissue is continuously remodeled through the concerted actions of bone cells, which include bone resorption by osteoclasts and bone formation by osteoblasts, whereas osteocytes act as mechanosensors and orchestrators of the bone remodeling process. This process is under the control of local (e.g., growth factors and cytokines) and systemic (e.g., calcitonin and estrogens) factors that all together contribute for bone homeostasis. An imbalance between bone resorption and formation can result in bone diseases including osteoporosis. Recently, it has been recognized that, during bone remodeling, there are an intricate communication among bone cells. For instance, the coupling from bone resorption to bone formation is achieved by interaction between osteoclasts and osteoblasts. Moreover, osteocytes produce factors that influence osteoblast and osteoclast activities, whereas osteocyte apoptosis is followed by osteoclastic bone resorption. The increasing knowledge about the structure and functions of bone cells contributed to a better understanding of bone biology. It has been suggested that there is a complex communication between bone cells and other organs, indicating the dynamic nature of bone tissue. In this review, we discuss the current data about the structure and functions of bone cells and the factors that influence bone remodeling.

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Antoine Martinez: Role: Academic Editor

Journal

Journal ID (nlm-ta): Int J Mol Sci

Journal ID (iso-abbrev): Int J Mol Sci

Journal ID (publisher-id): ijms

Title: International Journal of Molecular Sciences

Publisher: MDPI

ISSN (Electronic): 1422-0067

Publication date (Electronic): 04 February 2021

Publication date Collection: February 2021

Volume: 22

Issue: 4

Electronic Location Identifier: 1568

Affiliations

[1 ]I2MC, INSERM UMR 1297, University of Toulouse III, F-31000 Toulouse, France; noirrit.e@ 123456odonto-tlse.eu (E.N.-E.); marie.valera@ 123456inserm.fr (M.-C.V.); tremollieres.f@ 123456chu-toulouse.fr (F.T.); jean-francois.arnal@ 123456inserm.fr (J.-F.A.); francoise.lenfant@ 123456inserm.fr (F.L.); Coralie.fontaine@ 123456inserm.fr (C.F.)

[2 ]Department of Pediatric Dentistry, Faculty of Dental Surgery, University of Toulouse III, F-31000 Toulouse, France

[3 ]Menopause and Metabolic Bone Disease Center, Hôpital Paule de Viguier, University Hospital of Toulouse, F-31000 Toulouse, France

[4 ]Department of Periodontology, Faculty of Dental Surgery, University of Toulouse III, F-31000 Toulouse, France

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[* ]Correspondence: alexia.vinel@ 123456inserm.fr ; Tel.: +33-5-61-77-36-10

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Publisher ID: ijms-22-01568

DOI: 10.3390/ijms22041568

PMC ID: 7913980

PubMed ID: 33557249

SO-VID: e77b2b5e-f886-421e-97e1-ebe5c187e2aa

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Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

Critical Role of Estrogens on Bone Homeostasis in Both Male and Female: From Physiology to Medical Implications

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Higher order chromatin architecture

Most cited references 138

European guidance for the diagnosis and management of osteoporosis in postmenopausal women

From estrogen-centric to aging and oxidative stress: a revised perspective of the pathogenesis of osteoporosis.

Biology of Bone Tissue: Structure, Function, and Factors That Influence Bone Cells

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