Table_1_Between-Subject and Within-Subject Variation of Muscle Atrophy and Bone Loss in Response to Experimental Bed Rest.pdf

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.

为提升卧床干预个体应答反应的量化分析精度，我们针对参与8项不同卧床研究的76名受试者的小腿外周定量计算机断层扫描（peripheral quantitative computer tomography, pQCT）数据集展开分析。本研究采用全新开发的统计学方法，将测量不确定度（UMeas）与受试者间变异（between-subject-variation, BSV）、受试者内变异（within-subject variation, WSV）加以区分。研究结果显示，在近二十年的卧床研究中，测量不确定度下降了59.3%至80%（p < 0.01），且肌肉组织的测量不确定度高于骨骼。测量不确定度的降低可归因于测量流程的优化与标准化程度的提升。多数（59.1%）个体应答的pci超出了由测量不确定度定义的95%置信区间，这表明存在显著且可观的受试者间变异，且骨骼的受试者间变异大于肌肉，尤其在骨干测量位点处更为明显。骨位点间的相关性呈无统计学意义至弱正相关的水平，而肌肉位点间则呈现极强的正相关，这提示胫骨骨骼存在显著的受试者内变异，而小腿肌肉组织的受试者内变异则相对较弱。此外，骨内膜周长——这一反映个体骨骼几何形态的指标——可部分解释受试者内变异与受试者间变异。上述结果证实了骨骼存在显著的受试者间变异，且该变异部分由受试者内变异驱动，同时可能也受卧床前的体力活动与饮食习惯影响。此外，遗传与表观遗传变异或可解释受试者间变异，但无法解释受试者内变异。针对受试者内变异，骨骼特性差异与骨吸收过程或可作为其存在的解释依据。本研究同时证实了重复基线测量的重要性。最后，本研究为长期太空任务中部分有效对抗措施对应的最坏场景提供了理论依据。