Modeling trabecular bone adaptation to local bending load regulated by mechanosensing osteocytes

Cancellous bone has a complicated three-dimensional porous microstructure that consists of strut-like or plate-like trabeculae. The arrangement of the trabeculae is remodeled throughout the organism’s lifetime to functionally adapt to the surrounding mechanical environment. During bone remodeling, osteocytes buried in the bone matrix are believed to play a pivotal role as mechanosensory cells and help regulate the coupling of osteoclastic bone resorption and osteoblastic bone formation according to the mechanical stimuli. Previously, we constructed a mathematical model of trabecular bone remodeling incorporating cellular mechanosensing and intercellular signal transmission, in which osteocytes are assumed to sense the flow of interstitial fluid as a mechanical stimulus that regulates bone remodeling. Our remodeling simulation could describe the reorientation of a single strut-like trabecula under uniaxial loading. In the present study, to investigate the effects of a bending load on trabecular bone remodeling, we simulated the morphological change in a single trabecula under a cyclic bending load based on our mathematical model. The simulation results showed that the application of the bending load influences not only the formation of the plate-like trabecula but also the changes in trabecular topology. These results suggest the possibility that the characteristic trabecular morphology, such as the strut-like or plate-like form, is determined depending on the local mechanical environment

Interstitial fluid flow in canaliculi as a mechanical stimulus for cancellous bone remodeling: in silico validation

Cancellous bone has a dynamic 3-dimensional architecture of trabeculae, the arrangement of which is continually reorganized via bone remodeling to adapt to the mechanical environment. Osteocytes are currently believed to be the major mechanosensory cells and to regulate osteoclastic bone resorption and osteoblastic bone formation in response to mechanical stimuli. We previously developed a mathematical model of trabecular bone remodeling incorporating the possible mechanisms of cellular mechanosensing and intercellular communication in which we assumed that interstitial fluid flow activates the osteocytes to regulate bone remodeling. While the proposed model has been validated by the simulation of remodeling of a single trabecula, it remains unclear whether it can successfully represent in silico the functional adaptation of cancellous bone with its multiple trabeculae. In the present study, we demonstrated the response of cancellous bone morphology to uniaxial or bending loads using a combination of our remodeling model with the voxel finite element method. In this simulation, cancellous bone with randomly arranged trabeculae remodeled to form a well-organized architecture oriented parallel to the direction of loading, in agreement with the previous simulation results and experimental findings. These results suggested that our mathematical model for trabecular bone remodeling enables us to predict the reorganization of cancellous bone architecture from cellular activities. Furthermore, our remodeling model can represent the phenomenological law of bone transformation toward a locally uniform state of stress or strain at the trabecular level

Microscale fluid flow analysis in a human osteocyte canaliculus using a realistic high-resolution image-based three-dimensional model

Osteocytes play a pivotal role in the regulation of skeletal mass. Osteocyte processes are thought to sense the flow of interstitial fluid that is driven through the osteocyte canaliculi by mechanical stimuli placed upon bone, but how this flow elicits a cellular response is virtually unknown. Modern theoretical models assume that osteocyte canaliculi contain ultrastructural features that amplify the fluid flow-derived mechanical signal. Unfortunately the calcified bone matrix has considerably hampered studies on the osteocyte process within its canaliculus. Using one of the few ultra high voltage electron microscopes (UHVEM) available worldwide, we applied UHVEM tomography at 2 MeV to reconstruct unique three-dimensional images of osteocyte canaliculi in 1 μm sections of human bone. A realistic three-dimensional image-based model of a single canaliculus was constructed, and the fluid dynamics of a Newtonian fluid flow within the canaliculus was analyzed. We created virtual 2.2 nm thick sections through a canaliculus and found that traditional TEM techniques create a false impression that osteocyte processes are directly attached to the canalicular wall. The canalicular wall had a highly irregular surface and contained protruding axisymmetric structures similar in size and shape to collagen fibrils. We also found that the microscopic surface roughness of the canalicular wall strongly influenced the fluid flow profiles, whereby highly inhomogeneous flow patterns emerged. These inhomogeneous flow patterns may induce deformation of cytoskeletal elements in the osteocyte process, thereby amplifying mechanical signals. Based on these observations, new and realistic models can be developed that will significantly enhance our understanding of the process of mechanotransduction in bone