Between-Subject and Within-Subject Variation of Muscle Atrophy and Bone Loss in Response to Experimental Bed Rest

To improve quantification of individual responses to bed rest interventions, we analyzed peripheral quantitative computer tomography (pQCT) datasets of the lower leg of 76 participants, who took part in eight different bed rest studies. A newly developed statistical approach differentiated measureme...

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Main Authors: Jonas Böcker, Marie-Therese Schmitz, Uwe Mittag, Jens Jordan, Jörn Rittweger
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-02-01
Series:Frontiers in Physiology
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Online Access:https://www.frontiersin.org/articles/10.3389/fphys.2021.743876/full
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author Jonas Böcker
Marie-Therese Schmitz
Marie-Therese Schmitz
Uwe Mittag
Jens Jordan
Jens Jordan
Jörn Rittweger
Jörn Rittweger
author_facet Jonas Böcker
Marie-Therese Schmitz
Marie-Therese Schmitz
Uwe Mittag
Jens Jordan
Jens Jordan
Jörn Rittweger
Jörn Rittweger
author_sort Jonas Böcker
collection DOAJ
description To improve quantification of individual responses to bed rest interventions, we analyzed peripheral quantitative computer tomography (pQCT) datasets of the lower leg of 76 participants, who took part in eight different bed rest studies. A newly developed statistical approach differentiated measurement uncertainty UMeas from between-subject-variation (BSV) and within-subject variation (WSV). The results showed that UMeas decreased 59.3% to 80% over the two decades of bed rest studies (p < 0.01), and that it was higher for muscles than for bones. The reduction of UMeas could be explained by improved measurement procedures as well as a higher standardization. The majority (59.1%) of the individual responses pci exceeded the 95% confidence interval defined by UMeas, indicating significant and substantial BSV, which was greater for bones than for muscles, especially at the diaphyseal measurement sites. Non-significant to small positive inter-site correlations between bone sites, but very large positive inter-site correlation between muscle sites suggests that substantial WSV exists in the tibia bone, but much less so in the calf musculature. Furthermore, endocortical circumference, an indicator of the individual’s bone geometry could partly explain WSV and BSV. These results demonstrate the existence of substantial bone BSV, and that it is partly driven by WSV, and likely also by physical activity and dietary habits prior to bed rest. In addition, genetic and epigenetic variation could potentially explain BSV, but not WSV. As to the latter, differences of bone characteristics and the bone resorption process could offer an explanation for its existence. The study has also demonstrated the importance of duplicate baseline measurements. Finally, we provide here a rationale for worst case scenarios with partly effective countermeasures in long-term space missions.
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spelling doaj-art-f39b9da3bedd4e36bca4335a1f1137ef2025-01-03T09:49:32ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2022-02-011210.3389/fphys.2021.743876743876Between-Subject and Within-Subject Variation of Muscle Atrophy and Bone Loss in Response to Experimental Bed RestJonas Böcker0Marie-Therese Schmitz1Marie-Therese Schmitz2Uwe Mittag3Jens Jordan4Jens Jordan5Jörn Rittweger6Jörn Rittweger7Department of Muscle and Bone Metabolism, German Aerospace Center, Institute of Aerospace Medicine, Cologne, GermanyDepartment of Muscle and Bone Metabolism, German Aerospace Center, Institute of Aerospace Medicine, Cologne, GermanyInstitute of Medical Biometry, Informatics and Epidemiology (IMBIE), University Hospital Bonn, Bonn, GermanyDepartment of Muscle and Bone Metabolism, German Aerospace Center, Institute of Aerospace Medicine, Cologne, GermanyChair of Aerospace Medicine, University of Cologne, Cologne, GermanyGerman Aerospace Center, Head of Institute of Aerospace Medicine, Cologne, GermanyDepartment of Muscle and Bone Metabolism, German Aerospace Center, Institute of Aerospace Medicine, Cologne, GermanyDepartment of Pediatrics and Adolescent Medicine, University Hospital of Cologne, Cologne, GermanyTo improve quantification of individual responses to bed rest interventions, we analyzed peripheral quantitative computer tomography (pQCT) datasets of the lower leg of 76 participants, who took part in eight different bed rest studies. A newly developed statistical approach differentiated measurement uncertainty UMeas from between-subject-variation (BSV) and within-subject variation (WSV). The results showed that UMeas decreased 59.3% to 80% over the two decades of bed rest studies (p < 0.01), and that it was higher for muscles than for bones. The reduction of UMeas could be explained by improved measurement procedures as well as a higher standardization. The majority (59.1%) of the individual responses pci exceeded the 95% confidence interval defined by UMeas, indicating significant and substantial BSV, which was greater for bones than for muscles, especially at the diaphyseal measurement sites. Non-significant to small positive inter-site correlations between bone sites, but very large positive inter-site correlation between muscle sites suggests that substantial WSV exists in the tibia bone, but much less so in the calf musculature. Furthermore, endocortical circumference, an indicator of the individual’s bone geometry could partly explain WSV and BSV. These results demonstrate the existence of substantial bone BSV, and that it is partly driven by WSV, and likely also by physical activity and dietary habits prior to bed rest. In addition, genetic and epigenetic variation could potentially explain BSV, but not WSV. As to the latter, differences of bone characteristics and the bone resorption process could offer an explanation for its existence. The study has also demonstrated the importance of duplicate baseline measurements. Finally, we provide here a rationale for worst case scenarios with partly effective countermeasures in long-term space missions.https://www.frontiersin.org/articles/10.3389/fphys.2021.743876/fullbetween-subject variationwithin-subject variationmeasurement uncertaintybed restmuscle atrophybone loss
spellingShingle Jonas Böcker
Marie-Therese Schmitz
Marie-Therese Schmitz
Uwe Mittag
Jens Jordan
Jens Jordan
Jörn Rittweger
Jörn Rittweger
Between-Subject and Within-Subject Variation of Muscle Atrophy and Bone Loss in Response to Experimental Bed Rest
Frontiers in Physiology
between-subject variation
within-subject variation
measurement uncertainty
bed rest
muscle atrophy
bone loss
title Between-Subject and Within-Subject Variation of Muscle Atrophy and Bone Loss in Response to Experimental Bed Rest
title_full Between-Subject and Within-Subject Variation of Muscle Atrophy and Bone Loss in Response to Experimental Bed Rest
title_fullStr Between-Subject and Within-Subject Variation of Muscle Atrophy and Bone Loss in Response to Experimental Bed Rest
title_full_unstemmed Between-Subject and Within-Subject Variation of Muscle Atrophy and Bone Loss in Response to Experimental Bed Rest
title_short Between-Subject and Within-Subject Variation of Muscle Atrophy and Bone Loss in Response to Experimental Bed Rest
title_sort between subject and within subject variation of muscle atrophy and bone loss in response to experimental bed rest
topic between-subject variation
within-subject variation
measurement uncertainty
bed rest
muscle atrophy
bone loss
url https://www.frontiersin.org/articles/10.3389/fphys.2021.743876/full
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