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 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 vast majority (82.6%) 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 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.
Highlights
Microgravity exposure is associated with profound adaptations of the human body, including muscle atrophy and bone loss, both of are usually interpreted as a result of unloading and the lack of mechanical forces (Vico et al, 2000; LeBlanc et al, 2007; Fitts et al, 2010; Rittweger et al, 2018)
Differences between values of baseline data collection 1 (BDC1) and the within-subject means of the two baseline measurements were near-normally distributed without any substantial deviation, thereby justifying the approach outlined in the equations above
For computation of the measurement uncertainty UMeas, we used the results of the studies with two baseline measurements, meaning LTBR, RSL, and Valdoltra, respectively
Summary
Microgravity exposure is associated with profound adaptations of the human body, including muscle atrophy and bone loss, both of are usually interpreted as a result of unloading and the lack of mechanical forces (Vico et al, 2000; LeBlanc et al, 2007; Fitts et al, 2010; Rittweger et al, 2018). Besides BSV there is a within-subject variation (WSV) shown by differences in bone loss at different body sites after bed rest (Rittweger et al, 2005), the latter being a suitable analog of microgravity exposure on earth. CSA is a good approximation for muscle strength (Maughan et al, 1983; Rittweger et al, 2000; Fukunaga et al, 2001) Mitigating these profound adaptations and maintaining a sufficient physiological status is the aim of suitable countermeasures (Winnard et al, 2019). The variation may be explained by the fact that there are responders and non-responders toward a training intervention (Mann et al, 2014; Hecksteden et al, 2015; Ahtiainen et al, 2016) resulting in a BSV (McPhee et al, 2010; Ross et al, 2019)
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