Noninvasive in vivo monitoring of bone architecture alterations in hindlimb-unloaded female rats using novel three-dimensional microcomputed tomography

Introduction: Until now, data concerning structural changes of cancellous bone have only been available after necropsy of animals. In this study, we tested a novel microcomputed tomography (muCT) technique designed to monitor such changes repeatedly at a resolution of 26 mum with an acquisition time of about 10 minutes to map the entire proximal tibial metaphysis. Materials and Methods: Four-month-old female Wistar rats were randomized to seven groups of 10 animals to be either tail-suspended or to act as controls. muCT and DXA measurements were performed at 0, 7, 14, and 23 days in suspended and control rats. One group was killed at each of these time points, and bone samples were processed for histomorphometry and ex vivo muCT. Results: We verified that a good correlation was obtained between two-dimensional bone parameters evaluated in longitudinal tibial sections either by histomorphometry or muCT and muCT parameters obtained from either in vivo or ex vivo tibias. The longitudinal survey allowed earlier detection of both growth and unloading-related bone changes than the transverse survey. In controls, aging induced denser bones, reorganization of the trabecular network toward a more oriented plate-like structure, and an isotropic pattern. Unloading first inhibited cortical and cancellous bone growth and then induced bone loss characterized by fewer trabeculae, reduced connectivity density, and enhanced structure model index (SMI), revealing a lighter cancellous structure with development of rod-like characteristics. Conclusion: We show for the first time that this muCT prototype has a great potential to accurately, repeatedly, reliably, and rapidly investigate alterations of three-dimensional trabecular microarchitecture.