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      Skeletal adaptations in young male mice after 4 weeks aboard the International Space Station

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          Abstract

          Gravity has an important role in both the development and maintenance of bone mass. This is most evident in the rapid and intense bone loss observed in both humans and animals exposed to extended periods of microgravity in spaceflight. Here, cohabitating 9-week-old male C57BL/6 mice resided in spaceflight for ~4 weeks. A skeletal survey of these mice was compared to both habitat matched ground controls to determine the effects of microgravity and baseline samples in order to determine the effects of skeletal maturation on the resulting phenotype. We hypothesized that weight-bearing bones would experience an accelerated loss of bone mass compared to non-weight-bearing bones, and that spaceflight would also inhibit skeletal maturation in male mice. As expected, spaceflight had major negative effects on trabecular bone mass of the following weight-bearing bones: femur, tibia, and vertebrae. Interestingly, as opposed to the bone loss traditionally characterized for most weight-bearing skeletal compartments, the effects of spaceflight on the ribs and sternum resembled a failure to accumulate bone mass. Our study further adds to the insight that gravity has site-specific influences on the skeleton.

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          Most cited references24

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          Human Pathophysiological Adaptations to the Space Environment

          Space is an extreme environment for the human body, where during long-term missions microgravity and high radiation levels represent major threats to crew health. Intriguingly, space flight (SF) imposes on the body of highly selected, well-trained, and healthy individuals (astronauts and cosmonauts) pathophysiological adaptive changes akin to an accelerated aging process and to some diseases. Such effects, becoming manifest over a time span of weeks (i.e., cardiovascular deconditioning) to months (i.e., loss of bone density and muscle atrophy) of exposure to weightlessness, can be reduced through proper countermeasures during SF and in due time are mostly reversible after landing. Based on these considerations, it is increasingly accepted that SF might provide a mechanistic insight into certain pathophysiological processes, a concept of interest to pre-nosological medicine. In this article, we will review the main stress factors encountered in space and their impact on the human body and will also discuss the possible lessons learned with space exploration in reference to human health on Earth. In fact, this is a productive, cross-fertilized, endeavor in which studies performed on Earth yield countermeasures for protection of space crew health, and space research is translated into health measures for Earth-bound population.
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            The impact of microgravity on bone in humans.

            Experiencing real weightlessness in space is a dream for many of us who are interested in space research. Although space traveling fascinates us, it can cause both short-term and long-term health problems. Microgravity is the most important influence on the human organism in space. The human body undergoes dramatic changes during a long-term spaceflight. In this review, we will mainly focus on changes in calcium, sodium and bone metabolism of space travelers. Moreover, we report on the current knowledge on the mechanisms of bone loss in space, available models to simulate the effects of microgravity on bone on Earth as well as the combined effects of microgravity and cosmic radiation on bone. The available countermeasures applied in space will also be evaluated.
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              Skeletal health in long-duration astronauts: nature, assessment, and management recommendations from the NASA Bone Summit.

              Concern about the risk of bone loss in astronauts as a result of prolonged exposure to microgravity prompted the National Aeronautics and Space Administration to convene a Bone Summit with a panel of experts at the Johnson Space Center to review the medical data and research evidence from astronauts who have had prolonged exposure to spaceflight. Data were reviewed from 35 astronauts who had served on spaceflight missions lasting between 120 and 180 days with attention focused on astronauts who (1) were repeat fliers on long-duration missions, (2) were users of an advanced resistive exercise device (ARED), (3) were scanned by quantitative computed tomography (QCT) at the hip, (4) had hip bone strength estimated by finite element modeling, or (5) had lost >10% of areal bone mineral density (aBMD) at the hip or lumbar spine as measured by dual-energy X-ray absorptiometry (DXA). Because of the limitations of DXA in describing the effects of spaceflight on bone strength, the panel recommended that the U.S. space program use QCT and finite element modeling to further study the unique effects of spaceflight (and recovery) on bone health in order to better inform clinical decisions. Copyright © 2013 American Society for Bone and Mineral Research.
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                Author and article information

                Contributors
                +317 278-3482 , mkacena@iupui.edu
                Journal
                NPJ Microgravity
                NPJ Microgravity
                NPJ Microgravity
                Nature Publishing Group UK (London )
                2373-8065
                24 September 2019
                24 September 2019
                2019
                : 5
                : 21
                Affiliations
                [1 ]ISNI 0000 0001 2287 3919, GRID grid.257413.6, Department of Orthopaedic Surgery, , Indiana University School of Medicine, ; Indianapolis, IN USA
                [2 ]ISNI 0000 0000 9681 3540, GRID grid.280828.8, Richard L. Roudebush VA Medical Center, ; Indianapolis, IN USA
                [3 ]ISNI 0000 0001 2287 3919, GRID grid.257413.6, Biochemistry and Molecular Biology, , Indiana University School of Medicine, ; Indianapolis, IN USA
                [4 ]ISNI 0000 0001 2287 3919, GRID grid.257413.6, Microbiology and Immunology, , Indiana University School of Medicine, ; Indianapolis, IN USA
                [5 ]ISNI 0000 0001 2287 3919, GRID grid.257413.6, Anatomy and Cell Biology, , Indiana University School of Medicine, ; Indianapolis, IN USA
                [6 ]ISNI 0000 0000 9341 8465, GRID grid.420094.b, U.S. Army Center for Environmental Health Research, ; Fort Detrick, MD USA
                [7 ]ISNI 0000 0004 0646 0972, GRID grid.417469.9, Geneva Foundation, ; Fort Detrick, MD USA
                Article
                81
                10.1038/s41526-019-0081-4
                6760218
                297c4432-741c-4355-a95c-667a18ac5d98
                © The Author(s) 2019

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 20 March 2019
                : 22 August 2019
                Funding
                Funded by: FundRef https://doi.org/10.13039/100000002, U.S. Department of Health & Human Services | National Institutes of Health (NIH);
                Award ID: DK007519
                Award Recipient :
                Categories
                Article
                Custom metadata
                © The Author(s) 2019

                translational research,anatomy
                translational research, anatomy

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