Microarchitectural changes in the aging skeleton.

The age-related reduction in bone mass is disproportionally related to skeletal weakening, suggesting that microarchitectural changes are also important determinants of bone quality. The study of cortical and trabecular microstructure, which for many years was mainly based on two-dimensional histologic and scanning electron microscopy imaging, gained a tremendous momentum in the last decade and a half, due to the introduction of microcomputed tomography (μCT). This technology provides highly accurate qualitative and quantitative analyses based on three-dimensional images at micrometer resolution, which combined with finite elemental analysis predicts the biomechanical implications of microstructural changes. Global μCT analyses of trabecular bone have repeatedly suggested that the main age-related change in this compartment is a decrease in trabecular number with unaltered, or even increased, trabecular thickness. However, we show here that this may result from a bias whereby thick trabeculae near the cortex and the early clearance of thin struts mask authentic trabecular thinning. The main cortical age-related change is increased porosity due to negatively balanced osteonal remodeling and expansion of Haversian canals, which occasionally merge with endosteal and periosteal resorption bays, thus leading to rapid cortical thinning and cortical weakening. The recent emergence of CT systems with submicrometer resolution provides novel information on the age-related decrease in osteocyte lacunar density and related micropetrosis, the result of lacunar hypermineralization. Last but not least, the use of the submicrometer CT systems confirmed the occurrence of microcracks in the skeletal mineralized matrix and vastly advanced their morphologic characterization and mode of initiation and propagation.