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

Jonas Böcker; Marie-Therese Schmitz; Uwe Mittag; Jens Jordan; Jörn Rittweger

doi:10.3389/fphys.2021.743876

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

Front Physiol. 2022 Feb 22:12:743876. doi: 10.3389/fphys.2021.743876. eCollection 2021.

Authors

Jonas Böcker¹, Marie-Therese Schmitz^{1

2}, Uwe Mittag¹, Jens Jordan^{3

4}, Jörn Rittweger^{1

5}

Affiliations

¹ Department of Muscle and Bone Metabolism, German Aerospace Center, Institute of Aerospace Medicine, Cologne, Germany.
² Institute of Medical Biometry, Informatics and Epidemiology (IMBIE), University Hospital Bonn, Bonn, Germany.
³ Chair of Aerospace Medicine, University of Cologne, Cologne, Germany.
⁴ German Aerospace Center, Head of Institute of Aerospace Medicine, Cologne, Germany.
⁵ Department of Pediatrics and Adolescent Medicine, University Hospital of Cologne, Cologne, Germany.

Abstract

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 U _Meas from between-subject-variation (BSV) and within-subject variation (WSV). The results showed that U _Meas decreased 59.3-80% over the two decades of bed rest studies (p < 0.01), and that it was higher for muscles than for bones. The reduction of U _Meas could be explained by improved measurement procedures as well as a higher standardization. The vast majority (89.6%) of the individual responses pc _i exceeded the 95% confidence interval defined by U _Meas , indicating significant and substantial BSV, which was greater for bones than for muscles, especially at the epiphyseal 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 BSV bone, 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.

Keywords: bed rest; between-subject variation; bone loss; measurement uncertainty; muscle atrophy; within-subject variation.