No abstract

In the present study a rat animal model of lathyrism was employed to decipher whether anatomically confined alterations in collagen cross-links are sufficient to influence the mechanical properties of whole bone.Animal experiments were performed under an ethics committee approved protocol. Sixty-four female (47 day old) rats of equivalent weights were divided into four groups (16 per group): Controls were fed a semi-synthetic diet containing 0.6% calcium and 0.6% phosphorus for 2 or 4 weeks and β-APN treated animals were fed additionally with β-aminopropionitrile (0.1% dry weight). At the end of this period the rats in the four groups were sacrificed, and L2–L6 vertebra were collected. Collagen cross-links were determined by both biochemical and spectroscopic (Fourier transform infrared imaging (FTIRI)) analyses. Mineral content and distribution (BMDD) were determined by quantitative backscattered electron imaging (qBEI), and mineral maturity/crystallinity by FTIRI techniques. Micro-CT was used to describe the architectural properties. Mechanical performance of whole bone as well as of bone matrix material was tested by vertebral compression tests and by nano-indentation, respectively.The data of the present study indicate that β-APN treatment changed whole vertebra properties compared to non-treated rats, including collagen cross-links pattern, trabecular bone volume to tissue ratio and trabecular thickness, which were all decreased (p < 0.05). Further, compression tests revealed a significant negative impact of β-APN treatment on maximal force to failure and energy to failure, while stiffness was not influenced. Bone mineral density distribution (BMDD) was not altered either. At the material level, β-APN treated rats exhibited increased Pyd/Divalent cross-link ratios in areas confined to a newly formed bone. Moreover, nano-indentation experiments showed that the E-modulus and hardness were reduced only in newly formed bone areas under the influence of β-APN, despite a similar mineral content.In conclusion the results emphasize the pivotal role of collagen cross-links in the determination of bone quality and mechanical integrity. However, in this rat animal model of lathyrism, the coupled alterations of tissue structural properties make it difficult to weigh the contribution of the anatomically confined material changes to the overall mechanical performance of whole bone. Interestingly, the collagen cross-link ratio in bone forming areas had the same profile as seen in actively bone forming trabecular surfaces in human iliac crest biopsies of osteoporotic patients.

Finite element (FE) analysis has been applied for the past 40 years to simulate the mechanical behavior of bone. Although several validation studies have been performed on specific anatomical sites and load cases, this study aims to review the predictability of human bone strength at the three major osteoporotic fracture sites quantified in recently completed in vitro studies at our former institute. Specifically, the performance of FE analysis based on clinical computer tomography (QCT) is compared with the ones of the current densitometric standards, bone mineral content, bone mineral density (BMD) and areal BMD (aBMD). Clinical fractures were produced in monotonic axial compression of the distal radii, vertebral sections and in side loading of the proximal femora. QCT-based FE models of the three bones were developed to simulate as closely as possible the boundary conditions of each experiment. For all sites, the FE methodology exhibited the lowest errors and the highest correlations in predicting the experimental bone strength. Likely due to the improved CT image resolution, the quality of the FE prediction in the peripheral skeleton using high-resolution peripheral CT was superior to that in the axial skeleton with whole-body QCT. Because of its projective and scalar nature, the performance of aBMD in predicting bone strength depended on loading mode and was significantly inferior to FE in axial compression of radial or vertebral sections but not significantly inferior to FE in side loading of the femur. Considering the cumulated evidence from the published validation studies, it is concluded that FE models provide the most reliable surrogates of bone strength at any of the three fracture sites.

Different digital volume correlation (DVC) approaches are currently available or under development for bone tissue micromechanics. The aim of this study was to compare accuracy and precision errors of three DVC approaches for a particular three-dimensional (3D) zero-strain condition. Trabecular and cortical bone specimens were repeatedly scanned with a micro-computed tomography (CT). The errors affecting computed displacements and strains were extracted for a known virtual translation, as well as for repeated scans. Three DVC strategies were tested: two local approaches, based on fast-Fourier-transform (DaVis-FFT) or direct-correlation (DaVis-DC), and a global approach based on elastic registration and a finite element (FE) solver (ShIRT-FE). Different computation subvolume sizes were tested. Much larger errors were found for the repeated scans than for the virtual translation test. For each algorithm, errors decreased asymptotically for larger subvolume sizes in the range explored. Considering this particular set of images, ShIRT-FE showed an overall better accuracy and precision (a few hundreds microstrain for a subvolume of 50 voxels). When the largest subvolume (50-52 voxels) was applied to cortical bone, the accuracy error obtained for repeated scans with ShIRT-FE was approximately half of that for the best local approach (DaVis-DC). The difference was lower (250 microstrain) in the case of trabecular bone. In terms of precision, the errors shown by DaVis-DC were closer to the ones computed by ShIRT-FE (differences of 131 microstrain and 157 microstrain for cortical and trabecular bone, respectively). The multipass computation available for DaVis software improved the accuracy and precision only for the DaVis-FFT in the virtual translation, particularly for trabecular bone. The better accuracy and precision of ShIRT-FE, followed by DaVis-DC, were obtained with a higher computational cost when compared to DaVis-FFT. The results underline the importance of performing a quantitative comparison of DVC methods on the same set of samples by using also repeated scans, other than virtual translation tests only. ShIRT-FE provides the most accurate and precise results for this set of images. However, both DaVis approaches show reasonable results for large nodal spacing, particularly for trabecular bone. Finally, this study highlights the importance of using sufficiently large subvolumes, in order to achieve better accuracy and precision.