Future planetary habitats will expose inhabitants to both reduced gravity and hypoxia. This study investigated the effects of short-term unloading and normobaric hypoxia on whole body and regional body composition (BC). Eleven healthy, recreationally active, male participants with a mean (SD) age of 24 (2) years and body mass index of 22.4 (3.2) kg·m(-2) completed the following 3 10-day campaigns in a randomised, cross-over designed protocol: (i) hypoxic ambulatory confinement (HAMB; FIO2 = 0.147 (0.008); PIO2 = 93.8 (0.9) mm Hg), (ii) hypoxic bed rest (HBR; FIO2 = 0.147 (0.008); PIO2 = 93.8 (0.9) mm Hg), and (iii) normoxic bed rest (NBR; FIO2 = 0.209; PIO2 = 133.5 (0.7) mm Hg). Nutritional requirements were individually precalculated and the actual intake was monitored throughout the study protocol. Body mass, whole body, and regional BC were assessed before and after the campaigns using dual-energy X-ray absorptiometry. The calculated daily targeted energy intake values were 2071 (170) kcal for HBR and NBR and 2417 (200) kcal for HAMB. In both HBR and NBR campaigns the actual energy intake was within the targeted level, whereas in the HAMB the intake was lower than targeted (-8%, p < 0.05). Body mass significantly decreased in all 3 campaigns (-2.1%, -2.8%, and -2.0% for HAMB, HBR, and NBR, respectively; p < 0.05), secondary to a significant decrease in lean mass (-3.8%, -3.8%, -4.3% for HAMB, HBR, and NBR, respectively; p < 0.05) along with a slight, albeit not significant, increase in fat mass. The same trend was observed in the regional BC regardless of the region and the campaign. These results demonstrate that, hypoxia per se, does not seem to alter whole body and regional BC during short-term bed rest.

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New Findings What is the central question of this study?It is well established that muscle and bone atrophy in conditions of inactivity or unloading, but there is little information regarding the effect of a hypoxic environment on the time course of these deconditioning physiological systems. What is the main finding and its importance?The main finding is that a horizontal 10 day bed rest in normoxia results in typical muscle atrophy, which is not aggravated by hypoxia. Changes in bone mineral content or in metabolism were not detected after either normoxic or hypoxic bed rest. Abstract Musculoskeletal atrophy constitutes a typical adaptation to inactivity and unloading of weightbearing bones. The reduced‐gravity environment in future Moon and Mars habitats is likely to be hypobaric hypoxic, and there is an urgent need to understand the effect of hypoxia on the process of inactivity‐induced musculoskeletal atrophy. This was the principal aim of the present study. Eleven males participated in three 10 day interventions: (i) hypoxic ambulatory confinement; (ii) hypoxic bed rest; and (iii) normoxic bed rest. Before and after the interventions, the muscle strength (isometric maximal voluntary contraction), mass (lean mass, by dual‐energy X‐ray absorptiometry), cross‐sectional area and total bone mineral content (determined with peripheral quantitative computed tomography) of the participants were measured. Blood and urine samples were collected before and on the 1st, 4th and 10th day of the intervention and analysed for biomarkers of bone resorption and formation. There was a significant reduction in thigh and lower leg muscle mass and volume after both normoxic and hypoxic bed rests. Muscle strength loss was proportionately greater than the loss in muscle mass for both thigh and lower leg. There was no indication of bone loss. Furthermore, the biomarkers of resorption and formation were not affected by any of the interventions. There was no significant effect of hypoxia on the musculoskeletal variables. Short‐term normoxic (10 day) bed rest resulted in muscular deconditioning, but not in the loss of bone mineral content or changes in bone metabolism. Hypoxia did not modify these results.