Skeletal unloading during microgravity rapidly disrupts bone and metabolic homeostasis, yet sex-specific physiological responses remain poorly characterised. Dry immersion (DI), a ground-based analogue of microgravity, provides a model to investigate early determinants of unloading-induced bone deconditioning. We assessed sex differences in biochemical markers of bone and energy metabolism during two 5-day European Space Agency DI campaigns (VIVALDI 1 and 2) involving healthy males (n=19) and females (n=18). DI induced rapid alterations in bone remodelling in both sexes, characterised by increased bone resorption. TRAP5b increased more in females than in males (+22% vs. +11%; p=0.02), while CTX rose (+10%; p<0.05) only in females at DI completion. Bone formation markers declined similarly in both sexes, including PINP (−22% males, −19% females; p<0.001), osteocalcin, and carboxylated osteocalcin, whereas bone alkaline phosphatase increased, indicating dissociation between new matrix formation and mineralisation. Periostin decreased in both sexes but more markedly in females (−29%; p<0.001) and did not recover post-DI. Calcium increased transiently at DI-48 h (p<0.001), while PTH declined throughout immersion and recovery (p<0.001). IGF-1 (+8%; p<0.001) and visfatin (+63% males, +78% females; p<0.001) increased, with visfatin normalising post-DI only in females. Overall, although both sexes exhibited early bone deconditioning, females showed greater and more persistent resorption and periostin reduction, suggesting a faster progression toward bone loss. These early sex-specific responses identify potential biomarker that may enhance mechanistic understanding and guide the development of targeted countermeasures for spaceflight- and immobilisation-related bone loss.
Fernández et al. (2026) studied this question.