151. Mechanisms of osteocyte stimulation in osteoporosis
- Author
-
Ted J. Vaughan, Stefaan W. Verbruggen, Laoise M. McNamara, and ~
- Subjects
0301 basic medicine ,Trabecular bone ,Osteoporosis ,Hypoestrogenism ,Stimulation ,02 engineering and technology ,Bone tissue ,in-vivo ,Strain amplification ,Articular cartilage ,Mechanobiology ,Bone cell ,skin and connective tissue diseases ,Compact bone ,Cancellous bone ,Of the paper: Bone ,pulsating fluid-flow ,Finite element analysis ,Osteocyte ,in vivo ,medicine.anatomical_structure ,Mechanics of Materials ,Bone cells ,Female ,Biomedical engineering ,finite-element-analysis ,medicine.medical_specialty ,Materials science ,0206 medical engineering ,Osteocytes ,Bone and Bones ,Lacuna ,Biomaterials ,03 medical and health sciences ,Pulsating fluid flow ,Internal medicine ,medicine ,articular-cartilage ,Animals ,bone-cells ,Rats, Wistar ,Mechanical Engineering ,Chondrocyte pericellular matrix ,Estrogens ,Materials Engineering ,medicine.disease ,020601 biomedical engineering ,compact-bone ,Rats ,030104 developmental biology ,Endocrinology ,Stress, Mechanical - 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 that 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 oestrogen-deficient 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. (C) 2016 Elsevier Ltd. All rights reserved. The authors would like to acknowledge funding from the Irish Research Council (IRC) under the EMBARK program (S. W. V.), the European Research Council (ERC) under grant number 258992 (BONEMECHBIO) and the Irish Centre for High-End Computing (ICHEC). peer-reviewed 2018-05-10
- Published
- 2016