OSTEOPOROSIS

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Clinical treatments for osteoporosis, such as Hormone therapy (HT) and bisphosphonate drug treatments serve to reduce fracture susceptibility to a certain extent. However, drugs only reduce fracture susceptibility by 50%. This may be owing to the fact that the mechanisms initiating the disease are poorly understood. Although osteoporosis reduces overall bone mass causing bone fragility, recent studies from Prof. McNamara’s group have shown that bone tissue composition is also altered at the microscopic level, and that these changes are undetectable by conventional diagnostic techniques (DEXA), but may contribute to bone fracture. In particular we have shown that bone loss and tissue mineral changes during oestrogen deficiency do not occur ubiquitously, but are more prevalent at specific anatomical regions within the femora of rat and ovine models of osteoporosis.

Recent studies in Prof. McNamara’s group have found for the first time that these complex tissue levels changes in bone composition might be explained by alterations in bone cell biology, in particular the mechanobiological responses. Most interestingly we have recently shown that the mechanical environment of bone cells is altered during early-stage osteoporosis. This suggests that a mechanobiological response may have occurred to alter the mechanical environment, perhaps in an attempt to restore homeostasis.

 

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Osteocytes are believed to be the primary sensor of mechanical stimuli in bone, which orchestrate osteoblasts and osteoclasts to adapt bone structure and composition to meet physiological loading demands. Experimental studies to quantify the mechanical environment surrounding bone cells are challenging, and as such, computational and theoretical approaches have modelled either the solid or fluid environment of osteocytes to predict how these cells are stimulated in vivo. Osteocytes are an elastic cellular structure that deforms in response to the external fluid flow imposed by mechanical loading. This represents a most challenging multi-physics problem in which fluid and solid domains interact, and as such, no previous study has accounted for this complex behaviour.

The objective of this study is to employ fluid-structure interaction (FSI) modelling to investigate the complex mechanical environment of osteocytes in vivo. Fluorescent staining of osteocytes was performed in order to visualise their native environment and develop geometrically accurate models of the osteocyte in vivo. By simulating loading levels representative of vigorous physiological activity ([Formula: see text] compression and 300 Pa pressure gradient), we predict average interstitial fluid velocities [Formula: see text] and average maximum shear stresses [Formula: see text] surrounding osteocytes in vivo. Interestingly, these values occur in the canaliculi around the osteocyte cell processes and are within the range of stimuli known to stimulate osteogenic responses by osteoblastic cells in vitro. Significantly, our results suggest that the greatest mechanical stimulation of the osteocyte occurs in the cell processes, which, cell culture studies have indicated, is the most mechanosensitive area of the cell. These are the first computational FSI models to simulate the complex multi-physics mechanical environment of osteocyte in vivo and provide a deeper understanding of bone mechanobiology.