Globular structure of the hypermineralized tissue in human femoral neck

Bone becomes more fragile with ageing. Among many structural changes, a thin layer of highly mineralized and brittle tissue covers part of the external surface of the thin femoral neck cortex in older people and has been proposed to increase hip fragility. However, there have been very limited reports on this hypermineralized tissue in the femoral neck, especially on its ultrastructure. Such information is critical to understanding both the mineralization process and its contributions to hip fracture. Here, we use multiple advanced techniques to characterize the ultrastructure of the hypermineralized tissue in the neck across various length scales. Synchrotron radiation micro-CT found larger but less densely distributed cellular lacunae in hypermineralized tissue than in lamellar bone. When examined under FIB-SEM, the hypermineralized tissue was mainly composed of mineral globules with sizes varying from submicron to a few microns. Nano-sized channels were present within the mineral globules and oriented with the surrounding organic matrix. Transmission electron microscopy showed the apatite inside globules were poorly crystalline, while those at the boundaries between the globules had well-defined lattice structure with crystallinity similar to the apatite mineral in lamellar bone. No preferred mineral orientation was observed both inside each globule and at the boundaries. Collectively, we conclude based on these new observations that the hypermineralized tissue is non-lamellar and has less organized mineral, which may contribute to the high brittleness of the tissue.