Experimental and finite element analysis of the mouse caudal vertebrae loading model: prediction of cortical and trabecular bone adaptation

Abstract

In this study, we attempt to predict cortical and trabecular bone adaptation in the mouse caudal vertebrae loading model using knowledge of bone's local mechanical environment at the onset of loading. In a previous study, we demonstrated appreciable 25.9 and 11% increases in both trabecular and cortical bone volume density, respectively, when subjecting the fifth caudal vertebrae (C5) of C57BL/6 (B6) mice to an acute loading regime (amplitude of 8N, 3000 cycles, 10 Hz, 3 times a week for 4 weeks). We have also established a validated finite element (FE) model of the C5 vertebra using micro-computed tomography (micro-CT), which characterizes, in 3D, the micro-mechanical strains present in both cortical and trabecular compartments due to the applied loads. To investigate the relationship between load-induced bone adaptation and mechanical strains in-vivo and in-silico data sets were compared. Using data from the previous cross-sectional study, we divided cortical and trabecular compartments into 15 subregions and determined, for each region, a bone formation parameter ΔBV/BS (a cross-sectional measure of the bone volume added to cortical and trabecular surfaces following the described loading regime). Linear regression was then used to correlate mean regional values of ΔBV/BS with mean values of mechanical strains derived from the FE models which were similarly regionalized. The mechanical parameters investigated were strain energy density (SED), the orthogonal strains (e (x), e (y), e (z)) and the three shear strains (e (xy), e (yz), e (zx)). For cortical regions, regression analysis showed SED to correlate extremely well with ΔBV/BS (R (2) = 0.82) and e (z) (R (2) = 0.89). Furthermore, SED was found to predict expansion of the cortical shell correlating significantly with the regional percentage increases in cortical tissue volume (R (2) = 0.92), cortical marrow volume (R (2) = 0.91) and cortical thickness (R (2) = 0.56). For trabecular regions, FE parameters were found not to correlate with load-induced trabecular bone morphology. These results indicate that load-induced cortical morphology can be predicted from population data, whereas the prediction of trabecular morphology requires subject-specific micro- architecture.

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

“…The current study contributes to a growing understanding of the relationship between whole bone loading, bone tissue stress and strain, and mechanically induced bone formation. A correlation between bone formation and regions of increased tissue stress/strain was also observed in prior studies in mice and rats . In the current study, the ability of tissue stress and strain to predict locations of bone formation did not exceed 41% (the probability of observing bone formation at locations of greatest SED), a value that is slightly larger than our prior work in rats (32%) .…”

“…In a series of experiments examining the relationship between tissue stress, and strain and bone formation, Müller and colleagues used the rodent tail loading model with serial in vivo micro‐computed tomography imaging to observe longitudinal changes in cancellous bone microarchitecture caused by regular mechanical stimuli (3 days of cyclic loading/week). After 4–6 weeks of mechanical loading, bone density increased and locations of new bone formation were shown to be at regions of bone tissue experiencing larger tissue stresses . Recently, our group associated tissue stress and strain in cancellous bone with regions of bone formation over an even shorter time period (7 days after loading) .…”

Cortical Bony Thickening of the Lateral Intercondylar Wall: The Functional Attachment of the Anterior Cruciate Ligament

“…3,25 Osteoblasts respond to the stress placed upon them on a microscopic level, and therefore adaptations to bone mass and thickness occur at localized sites of high stress and only at the specific location of that stress. 11,29 Given that bone is so responsive to the forces placed upon it, it is highly likely that the patterns observed in our study are due to the stresses on the bone resulting from the ligamentous attachments. 26 The areas of thickness can The patterns observed are not the same as the total footprint of the ACL, which has been well described elsewhere, and clearly not all of the fibers of the ACL had a functional effect in these individuals.…”

Studying osteocytes within their environment

“…This ‘microfluidic imaging’ approach is reviewed in more detail elsewhere [64] but can be briefly described by the following workflow (Figure 7): 1) Bone formation and resorption are spatially mapped and quantified in a mouse loading model using in vivo μCT [65] and 3D image registration techniques [66]. 2) The micromechanical environment in loaded bone is determined by creating μFE models of the loaded bone from the initial CT image [67, 68]. 3) At the end of a specific loading regime, cryosectioning [69] and laser-capture-microdissection technologies are used to extract individual osteocytes [70] which are then processed (dna–micro-arrays, RT-PCR) using state-of-the-art lab-on-a-chip technologies [71].…”