Bone Brittleness Varies with Genetic Background in A/J and C57BL/6J Inbred Mice (original) (raw)
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Calcified Tissue International, 2008
The femoral neck is a relevant and sensitive site for studying the degree of osteopenia. Engineering principles predict that bone structural parameters, like cross-sectional geometry, are important determinants of bone mechanical parameters. Mechanical parameters are also directly affected by the material properties of the bone tissue. However, the relative importance of structural and material properties is still unknown. The aim of this study was to compare bone competence and structural parameters between a murine strain showing a low bone mass phenotype, C57BL/6 (B6), and another one showing a high bone mass phenotype, C3H/He (C3H), in order to better determine the role of bone structure and geometry in bone failure behavior. Murine femora of 12-and 16-week-old B6 and 12-and 16-week-old C3H inbred strains were mechanically tested under axial loading of the femoral head. In order to assess the structural properties, we performed three-dimensional morphometric analyses in five different compartments of the mouse femur using micro-computed tomography. The mechanical tests revealed that B6 femora became stiffer, stronger, and tougher at 12-16 weeks, while bone brittleness stayed constant. C3H bone stiffness increased, but strength remained constant, work to failure decreased, and bone became more brittle. These age effects indicated that B6 did not reach peak bone properties at 16 weeks of age and C3H did reach maximal skeletal biomechanical properties before 16 weeks of age. Our investigations showed that 83% of the strength of the femoral neck in the B6 strain was explained by cortical thickness at this location; in contrast, in C3H none of the mechanical properties of the femoral neck was explained by bone structural parameters. The relative contributions of bone structural and material properties on bone strength are different in B6 and C3H. We hypothesize that these different contributions are related to differences at the ultrastructural level of bone that affect bone failure.
European Journal of Medical Research, 2018
Objectives: Rat fracture models are extensively used to characterize normal and pathological bone healing. Despite, systematic research on inter-and intra-individual differences of common rat bones examined is surprisingly not available. Thus, we studied the biomechanical behaviour and radiological characteristics of the humerus, the tibia and the femur of the male Wistar rat-all of which are potentially available in the experimental situation-to identify useful or detrimental biomechanical properties of each bone and to facilitate sample size calculations. Methods: 40 paired femura, tibiae and humeri of male Wistar rats (10-38 weeks, weight between 240 and 720 g) were analysed by DXA, pQCT scan and three-point-bending. Bearing and loading bars of the biomechanical setup were adapted percentually to the bone's length. Subgroups of light (skeletal immature) rats under 400 g (N = 11, 22 specimens of each bone) and heavy (mature) rats over 400 g (N = 9, 18 specimens of each bone) were formed and evaluated separately. Results: Radiologically, neither significant differences between left and right bones, nor a specific side preference was evident. Mean side differences of the BMC were relatively small (1-3% measured by DXA and 2.5-5% by pQCT). Over all, bone mineral content (BMC) assessed by DXA and pQCT (TOT CNT, CORT CNT) showed high correlations between each other (BMC vs. TOT and CORT CNT: R 2 = 0.94-0.99). The load-displacement diagram showed a typical, reproducible curve for each type of bone. Tibiae were the longest bones (mean 41.8 ± 4.12 mm) followed by femurs (mean 38.9 ± 4.12 mm) and humeri (mean 29.88 ± 3.33 mm). Failure loads and stiffness ranged from 175.4 ± 45.23 N / 315.6 ± 63.00 N/mm for the femurs, 124.6 ± 41.13 N / 260.5 ± 59.97 N/mm for the humeri to 117.1 ± 3 3.94 N / 143.8 ± 36.99 N/mm for the tibiae. Smallest interindividual differences were observed in failure loads of the femurs (CV% 8.6) and tibiae (CV% 10.7) of heavy animals, light animals showed good consistency in failure loads of the humeri (CV% 7.7). Most consistent results of both sides (left vs. right) in failure loads were provided by the femurs of light animals (mean difference 4.0 ± 2.8%); concerning stiffness, humeri of heavy animals were most consistent (mean difference of 6.2 ± 5%). In general, the failure loads showed strong correlations to the BMC (R 2 = 0.85-0.88) whereas stiffness correlated only moderate, except for the humerus (BMC vs. stiffness: R 2 = 0.79). Discussion: Altogether, the rat's femur of mature specimens showed the most accurate and consistent radiological and biomechanical results. In synopsis with the common experimental use enabling comparison among different
Biological Basis of Bone Strength: Anatomy, Physiology and Measurement
Journal of Musculoskeletal and Neuronal Interactions, 2020
Understanding how bones are innately designed, robustly developed and delicately maintained through intricate anatomical features and physiological processes across the lifespan is vital to inform our assessment of normal bone health, and essential to aid our interpretation of adverse clinical outcomes affecting bone through primary or secondary causes. Accordingly this review serves to introduce new researchers and clinicians engaging with bone and mineral metabolism, and provide a contemporary update for established researchers or clinicians. Specifically, we describe the mechanical and non-mechanical functions of the skeleton; its multidimensional and hierarchical anatomy (macroscopic, microscopic, organic, inorganic, woven and lamellar features); its cellular and hormonal physiology (deterministic and homeostatic processes that govern and regulate bone); and processes of mechanotransduction, modelling, remodeling and degradation that underpin bone adaptation or maladaptation. In addition, we also explore commonly used methods for measuring bone metabolic activity or material features (imaging or biochemical markers) together with their limitations.
Molecular Genetic Studies of Bone Mechanical Strain and of Pedigrees With Very High Bone Density
2002
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Calcified Tissue International, 2008
Fracture susceptibility is heritable and dependent upon bone morphology and quality. However, studies of bone quality are typically overshadowed by emphasis on bone geometry and bone mineral density. Given that differences in mineral and matrix composition exist in a variety of species, we hypothesized that genetic variation in bone quality and tissue-level mechanical properties would also exist within species. Sixteen-week-old female A/J, C57BL/6J (B6), and C3H/HeJ (C3H) inbred mouse femora were analyzed using Fourier transform infrared imaging and tissue-level mechanical testing for variation in mineral composition, mineral maturity, collagen cross-link ratio, and tissuelevel mechanical properties. A/J femora had an increased mineral-to-matrix ratio compared to B6. The C3H mineral-to-matrix ratio was intermediate of A/J and B6. C3H femora had reduced acid phosphate and carbonate levels and an increased collagen cross-link ratio compared to A/J and B6. Modulus values paralleled mineral-to-matrix values, with A/J femora being the most stiff, B6 being the least stiff, and C3H having intermediate stiffness. In addition, work-to-failure varied among the strains, with the highly mineralized and brittle A/J femora performing the least amount of work-tofailure. Inbred mice are therefore able to differentially modulate the composition of their bone mineral and the maturity of their bone matrix in conjunction with tissue-level mechanical properties. These results suggest that specific combinations of bone quality and morphological traits are genetically regulated such that mechanically functional bones can be constructed in different ways.