Microgravity-related bone loss presents a challenge to astronauts undergoing long-duration spaceflight. Astronauts undergo a period of substantial bone apposition upon return to Earth, which provides a unique opportunity to examine the mechanisms of bone remodeling.

The objective of this study was to detect new trabecular bone connections in the form of topological bridging and quantify anisotropy changes in astronaut bone returning from the International Space Station (ISS).

Seventeen United States Orbital Segment (USOS) astronauts participating in ISS missions of varying lengths (3.5-7 months) had their distal tibia and radius imaged using high-resolution peripheral quantitative computed tomography (HR-pQCT) before spaceflight, at landing (R+0M), and at 12 months post-flight (R+12M).

Bone images were three-dimensionally rigid registered (3DR) longitudinally. A skeletonization decomposed the R+12M images to their underlying structure, allowing superimposition to the R+0M image where the difference highlighted areas of bone apposition during recovery. Anisotropy changes were tracked using mean intercept length (MIL).

To compare the sensitivity of topology and anisotropy changes in astronauts, a reference was established using same-day repeat HR-pQCT distal tibia (n=90) and radius (n=89) images from control participants. The topology and anisotropy difference significance was assessed using a Wilcoxon rank-sum test between astronauts and control, while the anisotropic precision was determined from control scan root-mean-square coefficient of variation (RMSCV%).

Astronauts’ group median apposition site average size was 1.2 times larger in the tibia and the same in the radius when compared to controls (p<0.01, p=0.64 respectively). Qualitatively examining the astronaut apposition sites revealed instances of bone bridging the space between two adjacent structures, indicating trabecular topological reconnection.

Estimated precision for anisotropy measures from the control scans ranged from 0.9 to 1.3%, while the astronauts’ change in anisotropy ranged from -2.9 to 6.4% (group median -0.02%) during in-flight loss and -5.0 to 6.8% (group median 0.1%) during post-flight recovery.

Bone resorption and apposition varied considerably between astronauts, with evidence of new topological connections across all participants. Several astronauts demonstrated a substantial change in anisotropy, suggesting directional alterations are concurrent with topology adaptation that occurs upon recovery on Earth.