Site specific bone loss induced by spaceflight in mice: a multiscale evaluation of trabecular and cortical structure and quality

Intrinsic quality, micro and nano structure of bone after 1 month of spaceflight and during 1 week of recovery had never been investigated. The aim was to explore these properties in appendicular and axial skeleton of mature mice.Ten C57/Bl6 male mice flew on the 30-day space Russian BION-M1 high-orbit satellite mission (Biomedical Ethics Commission of IBMP, n°319). Five were euthanized 12 h after landing, the others 8 days later. A ground control group was kept in the same conditions as in flight (housing, food and climate).Body weight, soleus muscle mass, and femur length were not significantly different between groups.In the femur, microgravity significantly decreased trabecular BV/TV (−65% vs Ctr) (micro-CT), increased trabecular and periosteal TRAP+ osteoclast surfaces and marrow adiposity (X22 vs Ctr), and decreased Ct.Th (−5.4% vs Ctr). Nano-indentation analysis indicated that cortical modulus, hardness and working energy were significantly decreased whereas the degree of mineralization (micro radiography) was not affected by microgravity. Microgravity did not affect cortical osteocyte lacuna density but decreased their mean 3D volume (Synchrotron Radiation nanotomography, nu003e8000 lacunae per sample). Eight days after landing, osteoclast cell surface were restored but trabecular BV/TV and Ct.Th remained lower than Ctr group.In vertebrae, microgravity significantly decreased BV/TV (−36% vs Ctr) and the modulus in the younger mineralized matrix which tended to increase after recovery. Degree of mineralization, mineral and collagen intrinsic quality (infra-red spectroscopy) were not changed by microgravity.To summarize, microgravity severely decreased bone mass, altered bone structure and intrinsic mechanical properties in both sites and increased femoral marrow adiposity. One week after landing, these properties tended to be rescued in vertebrae but remained altered in the femur despite normalized osteoclastic cell surfaces. The decrease of osteocyte lacunar volume suggests the existence of an intra-cortical bone preservation mechanism in absence of mechanical loading.