Local disruption of the canalicular network in ageing human bone

Bone remodelling is regulated by osteocytes and occurs through complementary functions of bone building and bone resorbing cells, osteoblasts and osteoclasts. Osteocytes are enclosed in lacunae interconnected via an extended 3D network of canaliculi to form the osteocyte lacuno-canalicular network (OLCN), crucial to maintaining mineralised bone homeostasis. Loss of bone strength and bone mineral density occurs with ageing, possibly related to an observed deterioration of network connectivity leading to an altered fluid flow through the OLCN, shown to be a regulator of the bone remodelling process. We propose to investigate OLCN network distortions using synchrotron X-Ray nano-holotomography (SR XNH) in osteons of healthy individuals of different age and in samples from patients carrying a mutation affecting the OLCN. The possibility of resolving single canaliculi will provide insight into the deterioration process of the OLCN, a possible contributor of age-related bone loss.