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      The Bones of Children With Obesity

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          Abstract

          Excess adiposity in childhood may affect bone development, ultimately leading to bone frailty. Previous reports showing an increased rate of extremity fractures in children with obesity support this fear. On the other hand, there is also evidence suggesting that bone mineral content is higher in obese children than in normal weight peers. Both adipocytes and osteoblasts derive from multipotent mesenchymal stem cells (MSCs) and obesity drives the differentiation of MSCs toward adipocytes at the expense of osteoblast differentiation. Furthermore, adipocytes in bone marrow microenvironment release a number of pro-inflammatory and immunomodulatory molecules that up-regulate formation and activation of osteoclasts, thus favoring bone frailty. On the other hand, body adiposity represents a mechanical load, which is beneficial for bone accrual. In this frame, bone quality, and structure result from the balance of inflammatory and mechanical stimuli. Diet, physical activity and the hormonal milieu at puberty play a pivotal role on this balance. In this review, we will address the question whether the bone of obese children and adolescents is unhealthy in comparison with normal-weight peers and discuss mechanisms underlying the differences in bone quality and structure. We anticipate that many biases and confounders affect the clinical studies conducted so far and preclude us from achieving robust conclusions. Sample-size, lack of adequate controls, heterogeneity of study designs are the major drawbacks of the existing reports. Due to the increased body size of children with obesity, dual energy absorptiometry might overestimate bone mineral density in these individuals. Magnetic resonance imaging, peripheral quantitative CT (pQCT) scanning and high-resolution pQCT are promising techniques for the accurate estimate of bone mineral content in obese children. Moreover, no longitudinal study on the risk of incident osteoporosis in early adulthood of children and adolescents with obesity is available. Finally, we will address emerging dietary issues (i.e., the likely benefits for the bone health of polyunsaturated fatty acids and polyphenols) since an healthy diet (i.e., the Mediterranean diet) with balanced intake of certain nutrients associated with physical activity remain the cornerstones for achieving an adequate bone accrual in young individuals regardless of their adiposity degree.

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          Most cited references169

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          Estrogen and the skeleton.

          Estrogen is the major hormonal regulator of bone metabolism in women and men. Therefore, there is considerable interest in unraveling the pathways by which estrogen exerts its protective effects on bone. Although the major consequence of the loss of estrogen is an increase in bone resorption, estrogen deficiency is associated with a gap between bone resorption and formation, indicating that estrogen is also important for maintaining bone formation at the cellular level. Direct estrogen effects on osteocytes, osteoclasts, and osteoblasts lead to inhibition of bone remodeling, decreased bone resorption, and maintenance of bone formation, respectively. Estrogen also modulates osteoblast/osteocyte and T-cell regulation of osteoclasts. Unraveling these pleiotropic effects of estrogen may lead to new approaches to prevent and treat osteoporosis. Copyright © 2012 Elsevier Ltd. All rights reserved.
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            Adult haematopoietic stem cell niches

            Recent advances in imaging techniques and genetic tools have rapidly increased our understanding of the niches that maintain adult haematopoietic stem cells, including the constituent cell types and the factors that directly or indirectly regulate these niches.
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              Leptin inhibits bone formation through a hypothalamic relay: a central control of bone mass.

              Gonadal failure induces bone loss while obesity prevents it. This raises the possibility that bone mass, body weight, and gonadal function are regulated by common pathways. To test this hypothesis, we studied leptin-deficient and leptin receptor-deficient mice that are obese and hypogonadic. Both mutant mice have an increased bone formation leading to high bone mass despite hypogonadism and hypercortisolism. This phenotype is dominant, independent of the presence of fat, and specific for the absence of leptin signaling. There is no leptin signaling in osteoblasts but intracerebroventricular infusion of leptin causes bone loss in leptin-deficient and wild-type mice. This study identifies leptin as a potent inhibitor of bone formation acting through the central nervous system and therefore describes the central nature of bone mass control and its disorders.

                Author and article information

                Contributors
                Journal
                Front Endocrinol (Lausanne)
                Front Endocrinol (Lausanne)
                Front. Endocrinol.
                Frontiers in Endocrinology
                Frontiers Media S.A.
                1664-2392
                24 April 2020
                2020
                : 11
                : 200
                Affiliations
                [1] 1Endocrinology Unit, Pediatric University Department, Bambino Gesù Children's Hospital , Rome, Italy
                [2] 2Diabetes and Growth Disorders Unit, Dipartimento Pediatrico Universitario Ospedaliero Bambino Gesù Children's Hospital, Tor Vergata University , Rome, Italy
                [3] 3Department of Women's and Children's Health, Karolinska Institute and University Hospital , Stockholm, Sweden
                [4] 4Pediatric Clinic, Department of Surgical and Biomedical Sciences, University of Perugia , Perugia, Italy
                [5] 5Pediatric Resident, Pediatric Clinic, University of Brescia , Brescia, Italy
                [6] 6Research Area for Multifactorial Diseases, Bambino Gesù Children's Hospital , Rome, Italy
                Author notes

                Edited by: Amélie E. Coudert, Université Paris Diderot, France

                Reviewed by: Maria Felicia Faienza, University of Bari Aldo Moro, Italy; Connie M. Weaver, Purdue University, United States

                *Correspondence: Danilo Fintini danilo.fintini@ 123456opbg.net

                This article was submitted to Bone Research, a section of the journal Frontiers in Endocrinology

                †These authors have contributed equally to this work

                Article
                10.3389/fendo.2020.00200
                7193990
                32390939
                1f9fb838-6be8-4760-b79d-024810362866
                Copyright © 2020 Fintini, Cianfarani, Cofini, Andreoletti, Ubertini, Cappa and Manco.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 06 December 2019
                : 20 March 2020
                Page count
                Figures: 2, Tables: 4, Equations: 0, References: 197, Pages: 16, Words: 14281
                Categories
                Endocrinology
                Review

                Endocrinology & Diabetes
                bone,child,inflammation,lifestyle,obesity,physical activity,polyphenols,polyunsaturated fatty acids

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