A novel<i>in vivo</i>mouse model for mechanically stimulated bone adaptation – a combined experimental and computational validation study

Webster, Duncan J.; Morley, Philip L.; Lenthe, G. Harry van; Müller, Ralph

doi:10.1080/10255840802078014

Cited by 82 publications

(87 citation statements)

References 16 publications

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“…In short: fifteen-week-old female C57BL/6 mice underwent axial compressive loading of the sixth caudal vertebrae at either 8 N (loaded group; n = 8) or 0 N (control group; n = 8) for 3,000 cycles at 10 Hz three times per week for four weeks and weekly in vivo micro-computed tomography (micro-CT) scans. Loading was applied through pins inserted in adjacent vertebrae using a recently developed caudal vertebra axial compression device (CVAD) (Webster et al 2008(Webster et al , 2010. During the remaining period, mice were able to freely move their tail.…”

Section: Murine Caudal Vertebra Modelsmentioning

confidence: 99%

Bone morphology allows estimation of loading history in a murine model of bone adaptation

Christen

Rietbergen

Lambers

et al. 2011

Biomech Model Mechanobiol

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Bone adapts its morphology (density/microarchitecture) in response to the local loading conditions in such a way that a uniform tissue loading is achieved ('Wolff's law'). This paradigm has been used as a basis for bone remodeling simulations to predict the formation and adaptation of trabecular bone. However, in order to predict bone architectural changes in patients, the physiological external loading conditions, to which the bone was adapted, need to be determined. In the present study, we developed a novel bone loading estimation method to predict such external loading conditions by calculating the loading history that produces the most uniform bone tissue loading. We applied this method to murine caudal vertebrae of two groups that were in vivo loaded by either 0 or 8 N, respectively. Plausible load cases were sequentially applied to micro-finite element models of the mice vertebrae, and scaling factors were calculated for each load case to derive the most uniform tissue strainenergy density when all scaled load cases are applied simultaneously. The bone loading estimation method was able to predict the difference in loading history of the two groups and the correct load magnitude for the loaded group. This result suggests that the bone loading history can be estimated from its morphology and that such a method could be useful for predicting the loading history for bone remodeling studies or at sites where measurements are difficult, as in bone in vivo or fossil bones.

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Section: Murine Caudal Vertebra Modelsmentioning

confidence: 99%

Bone morphology allows estimation of loading history in a murine model of bone adaptation

Christen

Rietbergen

Lambers

et al. 2011

Biomech Model Mechanobiol

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“…All voxels were converted to eight-node brick elements, rendering models of approximately 1.8 million elements. For both the bone and the disc a Young's modulus of 14.8 GPa and a Poisson ratio of 0.3 were assigned to each element, as previously validated for caudal vertebrae [33]. The top was displaced 0.1%, while the bottom was constrained in all directions.…”

Section: Finite Element Analysismentioning

confidence: 99%

Longitudinal Assessment of In Vivo Bone Dynamics in a Mouse Tail Model of Postmenopausal Osteoporosis

et al. 2011

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Recently, it has been shown that transient bone biology can be observed in vivo using time-lapse microcomputed tomography (lCT) in the mouse tail bone. Nevertheless, in order for the mouse tail bone to be a model for human disease, the hallmarks of any disease must be mimicked. The aim of this study was to investigate whether postmenopausal osteoporosis could be modeled in caudal vertebrae of C57Bl/6 mice, considering static and dynamic bone morphometry as well as mechanical properties, and to describe temporal changes in bone remodeling rates. Twenty C57Bl/6 mice were ovariectomized (OVX, n = 11) or sham-operated (SHM, n = 9) and monitored with in vivo lCT on the day of surgery and every 2 weeks after, up to 12 weeks. There was a significant decrease in bone volume fraction for OVX (-35%) compared to SHM (?16%) in trabecular bone (P \ 0.001). For OVX, highturnover bone loss was observed, with the bone resorption rate exceeding the bone formation rate (P \ 0.001). Furthermore there was a significant decrease in whole-bone stiffness for OVX (-16%) compared to SHM (?11%, P \ 0.001). From these results we conclude that the mouse tail vertebra mimics postmenopausal bone loss with respect to these parameters and therefore might be a suitable model for postmenopausal osteoporosis. When evaluating temporal changes in remodeling rates, we found that OVX caused an immediate increase in bone resorption rate (P \ 0.001) and a delayed increase in bone formation rate (P \ 0.001). Monitoring transient bone biology is a promising method for future research.

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“…This hypothesis was investigated by comparing the results of the simulation with real cross-sectional animal data gained from an experimental loading model, which was established to investigate the behaviour of bone in response to superphysiological loads. More details with respect to this model can be found elsewhere (Webster et al 2008). Briefly, the fifth caudal vertebrae (C5) of 4 groups of 10 C57BL/6 (B6), 12-week-old, female mice were loaded in vivo with amplitudes of 0 (control), 2, 4 and 8 N, respectively, using a mechanical loading device (3000 cycles, 10 Hz, three times a week for four weeks).…”

Section: (C ) Extending and Validating A Model For Bone Adaptationmentioning

confidence: 99%

In silico biology of bone modelling and remodelling: adaptation

Gerhard

Webster

Lenthe

et al. 2009

Phil. Trans. R. Soc. A.

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Modelling and remodelling are the processes by which bone adapts its shape and internal structure to external influences. However, the cellular mechanisms triggering osteoclastic resorption and osteoblastic formation are still unknown. In order to investigate current biological theories, in silico models can be applied. In the past, most of these models were based on the continuum assumption, but some questions related to bone adaptation can be addressed better by models incorporating the trabecular microstructure. In this paper, existing simulation models are reviewed and one of the microstructural models is extended to test the hypothesis that bone adaptation can be simulated without particular knowledge of the local strain distribution in the bone. Validation using an experimental murine loading model showed that this is possible. Furthermore, the experimental model revealed that bone formation cannot be attributed only to an increase in trabecular thickness but also to structural reorganization including the growth of new trabeculae. How these new trabeculae arise is still an unresolved issue and might be better addressed by incorporating other levels of hierarchy, especially the cellular level. The cellular level sheds light on the activity and interplay between the different cell types, leading to the effective change in the whole bone. For this reason, hierarchical multi-scale simulations might help in the future to better understand the biomathematical laws behind bone adaptation.

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A novelin vivomouse model for mechanically stimulated bone adaptation – a combined experimental and computational validation study

Cited by 82 publications

References 16 publications

Bone morphology allows estimation of loading history in a murine model of bone adaptation

Bone morphology allows estimation of loading history in a murine model of bone adaptation

Longitudinal Assessment of In Vivo Bone Dynamics in a Mouse Tail Model of Postmenopausal Osteoporosis

In silico biology of bone modelling and remodelling: adaptation

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