Mechanisms of osteocyte stimulation in osteoporosis

Abstract

Experimental studies have shown that primary osteoporosis caused by oestrogen-deficiency results in localised alterations in bone tissue properties and mineral composition. Additionally, changes to the lacunar-canalicular architecture surrounding the mechanosensitive osteocyte have been observed in animal models of the disease. Recently, it has also been demonstrated that the mechanical stimulation sensed by osteocytes changes significantly during osteoporosis.Specifically, it was shown osteoporotic bone cells experience higher maximum strains than healthy bone cells after short durations of oestrogen deficiency. However, in long-term oestrogen deficiency there was no significant difference between bone cells in healthy and normal bone. The mechanisms by which these changes arise are unknown. In this study, we test the hypothesis that complex changes in tissue composition and lacunar-canalicular architecture during osteoporosis alter the mechanical stimulation of the osteocyte. The objective of this research is to employ computational methods to investigate the relationship between changes in bone tissue composition and microstructure and the mechanical stimulation of osteocytes during osteoporosis. By simulating physiological loading, it was observed that an initial decrease in tissue stiffness (of 0.425 GPa) and mineral content (of 0.66 wt% Ca) relative to controls could explain the mechanical stimulation observed at the early stages of oestrogen deficiency (5 weeks post-OVX) during in situ bone cell loading in an oestrogendeficient rat model of post-menopausal osteoporosis (Verbruggen et al. 2015). Moreover, it was found that a later increase in stiffness (of 1.175 GPa) and mineral content (of 1.64 wt% Ca) during long-term osteoporosis (34 weeks post-OVX), could explain the mechanical stimuli previously observed at a later time point due to the progression of osteoporosis. Furthermore, changes in canalicular tortuosity arising during osteoporosis were shown to result in increased osteogenic strain stimulation, though to a lesser extent than has been observed experimentally.The findings of this study indicate that changes in the extracellular environment during osteoporosis, arising from altered mineralisation and lacunar-canalicular architecture, lead to altered mechanical stimulation of osteocytes, and provide an enhanced understanding of changes in bone mechanobiology during osteoporosis.

Mechanically induced bone formation is not sensitive to local osteocyte density in rat vertebral cancellous bone

“…A more detailed representation of the lacunar‐canalicular network geometry and connectivity that accounts for the relationship between tissue strains, and fluid shears would be needed to further clarify this effect. Additionally, recent computational models suggest that size and shape of the canaliculi affect fluid velocities and therefore the fluid shear stress experienced by an osteocyte . Alignment and shape of osteocyte lacunae have also been shown to effect the stresses experienced by osteocytes .…”

“…Additionally, recent computational models suggest that size and shape of the canaliculi affect fluid velocities and therefore the fluid shear stress experienced by an osteocyte. 42,43 Alignment and shape of osteocyte lacunae have also been shown to effect the stresses experienced by osteocytes. 44 It is possible that these nano-scale aspects of geometry within the lacunar-canalicular system may be more influential in determining the locations of mechanically induced bone formation than the number of osteocytes alone.…”

Finite Element Study of the Effect of Osteon Morphology Variation Related Ageing, Osteoporosis, or Physical Activity Level on Its Poroelastic Behaviors

“…Variations in the morphol-ogy of osteon have been investigated in osteoporosis, and these alterations include more circular osteons and thinning of wall-thickness. The findings of this study suggest that the alterations of osteon morphology during osteoporosis can lead to decrease of the P and V, and may alter mechanical stimulation of osteocyte-lacunar-canalicular system 37) . This research provides a new way to elucidate how morphologic changes of the osteon alter the mechanical stimulation of osteocyte-lacunar-canalicular system.…”

In silico bone mechanobiology: modeling a multifaceted biological system

“…In contrast to CFD, the first complete 3D idealized FE model of a whole osteocyte lacuna was developed later, and predicted that strains in the lacunar walls are amplified by a factor of 1.26–1.52 for an applied global strain of 2000 με, increasing to a factor of 3 with the inclusion of canaliculi in the simulations (Figure (a)). While these studies employed idealized geometries, recent FE studies generated accurate 3D geometries of whole osteocytes using confocal laser scanning microscopy, predicting that geometry alone can amplify strain transfer to the osteocyte in vivo , both in healthy and osteoporotic bone . This was further corroborated by highly detailed FE models generated with geometries of the lacunar–canalicular network captured with synchrotron X‐ray nano‐tomography, which predicted strain amplification of up to a factor of 70 (Figure (b)).…”