9 research outputs found
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Micromechanics of Human Bone: Role of Architecture and Tissue Material Properties
Knowledge of the biomechanical behavior and failure mechanisms of human bone is fundamental to understanding the etiology of bone fractures as well as the mechanisms by which aging, disease, and treatment can alter the mechanical competence of bone. In this context, the focus of this dissertation was to enhance the current understanding of the biomechanical mechanisms of bone strength, and more specifically, to elucidate the role of architecture and tissue material properties in overall bone strength and whole-bone failure behavior.Using the latest advances in micro-computed tomography and high-resolution finite element modeling, we investigated the effect of typical population-variations in tissue-level ductility on human vertebral strength. We found that compared to the reference case, varying both cortical and trabecular tissue ultimate strains by ±1 SD from their mean values changed vertebral strength by at most ±8%, an effect that was relatively uniform across all the specimens. Overall strength changed similarly for similar (±1 SD) changes in trabecular versus cortical ductility. Further analysis revealed that only a tiny proportion of tissue failed (< 2%) when the whole bone reached its point of structure-level failure, and that the failure mode and location of this tiny amount were relatively insensitive to typical variations in tissue ductility. These findings suggest that it is the overall load transfer within the whole vertebral body —determined by bone volume fraction and microstructure— that dictates where failure occurs rather than typical variations in the ductility of the tissue. Together these findings suggest that typical variations in tissue ductility might have a relatively modest impact on vertebral strength compared to the multiple-fold variations in vertebral strength that are typically observed across any elderly population.Combining micro-computed tomography, high-resolution finite element modeling and biomechanical testing, we sought to provide further insight into the tissue modulus of trabecular bone and better elucidate its relation with bone volume fraction and trabecular microarchitecture. Our results indicated that effective tissue modulus of vertebral trabecular bone varied greatly among the specimens and was negatively correlated with bone volume fraction of each vertebra (R2 = 0.51, p < 0.05). These results suggest that there can be 3X variation in tissue modulus across the elderly human vertebrae, about 50% of which may be explained by variations in bone volume fraction. Together these findings suggest that as trabecular bone becomes older and thus more porous due to an imbalance between bone formation and resorption, the tissue may become stiffer to compensate for the bone loss.The work presented in this dissertation has also provided substantial insight into the structure–function relations for trabecular bone from different anatomic sites. We investigated the main structure–function relation —characterized by bone volume fraction versus on-axis yield stress— for human calcaneal trabecular bone and compared this relation to that for trabecular bone from other anatomic sites. We found that the relation between yield stress and bone volume fraction of the calcaneus was most similar to that of the proximal tibia. Furthermore, our results demonstrated that while there was no universal yield stress–bone volume fraction relation for trabecular bone across different anatomic sites for on-axis loading, the general (normalized) yield stress–bone volume fraction relation was similar for all sites. This similarity in the normalized relation suggests that a given percentage deviation from the mean bone mass has the same mechanical consequence at the calcaneus as it does at the other anatomic sites.In closure, this dissertation provides answers to some of the fundamental questions regarding the role of architecture and tissue material properties in explaining the variations in overall bone strength across individuals, and provides new insight into the etiology of age-related fractures. This work also outlines potential areas of future research to further advance our current understanding of overall bone strength and fracture etiology
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Micromechanics of Human Bone: Role of Architecture and Tissue Material Properties
Knowledge of the biomechanical behavior and failure mechanisms of human bone is fundamental to understanding the etiology of bone fractures as well as the mechanisms by which aging, disease, and treatment can alter the mechanical competence of bone. In this context, the focus of this dissertation was to enhance the current understanding of the biomechanical mechanisms of bone strength, and more specifically, to elucidate the role of architecture and tissue material properties in overall bone strength and whole-bone failure behavior.Using the latest advances in micro-computed tomography and high-resolution finite element modeling, we investigated the effect of typical population-variations in tissue-level ductility on human vertebral strength. We found that compared to the reference case, varying both cortical and trabecular tissue ultimate strains by ±1 SD from their mean values changed vertebral strength by at most ±8%, an effect that was relatively uniform across all the specimens. Overall strength changed similarly for similar (±1 SD) changes in trabecular versus cortical ductility. Further analysis revealed that only a tiny proportion of tissue failed (< 2%) when the whole bone reached its point of structure-level failure, and that the failure mode and location of this tiny amount were relatively insensitive to typical variations in tissue ductility. These findings suggest that it is the overall load transfer within the whole vertebral body —determined by bone volume fraction and microstructure— that dictates where failure occurs rather than typical variations in the ductility of the tissue. Together these findings suggest that typical variations in tissue ductility might have a relatively modest impact on vertebral strength compared to the multiple-fold variations in vertebral strength that are typically observed across any elderly population.Combining micro-computed tomography, high-resolution finite element modeling and biomechanical testing, we sought to provide further insight into the tissue modulus of trabecular bone and better elucidate its relation with bone volume fraction and trabecular microarchitecture. Our results indicated that effective tissue modulus of vertebral trabecular bone varied greatly among the specimens and was negatively correlated with bone volume fraction of each vertebra (R2 = 0.51, p < 0.05). These results suggest that there can be 3X variation in tissue modulus across the elderly human vertebrae, about 50% of which may be explained by variations in bone volume fraction. Together these findings suggest that as trabecular bone becomes older and thus more porous due to an imbalance between bone formation and resorption, the tissue may become stiffer to compensate for the bone loss.The work presented in this dissertation has also provided substantial insight into the structure–function relations for trabecular bone from different anatomic sites. We investigated the main structure–function relation —characterized by bone volume fraction versus on-axis yield stress— for human calcaneal trabecular bone and compared this relation to that for trabecular bone from other anatomic sites. We found that the relation between yield stress and bone volume fraction of the calcaneus was most similar to that of the proximal tibia. Furthermore, our results demonstrated that while there was no universal yield stress–bone volume fraction relation for trabecular bone across different anatomic sites for on-axis loading, the general (normalized) yield stress–bone volume fraction relation was similar for all sites. This similarity in the normalized relation suggests that a given percentage deviation from the mean bone mass has the same mechanical consequence at the calcaneus as it does at the other anatomic sites.In closure, this dissertation provides answers to some of the fundamental questions regarding the role of architecture and tissue material properties in explaining the variations in overall bone strength across individuals, and provides new insight into the etiology of age-related fractures. This work also outlines potential areas of future research to further advance our current understanding of overall bone strength and fracture etiology
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High-precision method for cyclic loading of small-animal vertebrae to assess bone quality.
One potentially important bone quality characteristic is the response of bone to cyclic (repetitive) mechanical loading. In small animals, such as in rats and mice, cyclic loading experiments are particularly challenging to perform in a precise manner due to the small size of the bones and difficult-to-eliminate machine compliance. Addressing this issue, we developed a precise method for ex vivo cyclic compressive loading of isolated mouse vertebral bodies. The method has three key characteristics: 3D-printed support jigs for machining plano-parallel surfaces of the tiny vertebrae; pivotable loading platens to ensure uniform contact and loading of specimen surfaces; and specimen-specific micro-CT-based finite element analysis to measure stiffness to prescribe force levels that produce the same specified level of strain for all test specimens. To demonstrate utility, we measured fatigue life for three groups (n = 5-6 per group) of L5 vertebrae of C57BL/6J male mice, comparing our new method against two methods commonly used in the literature. We found reduced scatter of the mechanical behavior for this new method compared to the literature methods. In particular, for a controlled level of strain, the standard deviation of the measured fatigue life was up to 5-fold lower for the new method (F-ratio = 4.9; p < 0.01). The improved precision for this new method for biomechanical testing of small-animal vertebrae may help elucidate aspects of bone quality
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Relationships among ultrasonic and mechanical properties of cancellous bone in human calcaneus in vitro.
Clinical bone sonometers applied at the calcaneus measure broadband ultrasound attenuation and speed of sound. However, the relation of ultrasound measurements to bone strength is not well-characterized. Addressing this issue, we assessed the extent to which ultrasonic measurements convey in vitro mechanical properties in 25 human calcaneal cancellous bone specimens (approximately 2×4×2cm). Normalized broadband ultrasound attenuation, speed of sound, and broadband ultrasound backscatter were measured with 500kHz transducers. To assess mechanical properties, non-linear finite element analysis, based on micro-computed tomography images (34-micron cubic voxel), was used to estimate apparent elastic modulus, overall specimen stiffness, and apparent yield stress, with models typically having approximately 25-30 million elements. We found that ultrasound parameters were correlated with mechanical properties with R=0.70-0.82 (p<0.001). Multiple regression analysis indicated that ultrasound measurements provide additional information regarding mechanical properties beyond that provided by bone quantity alone (p≤0.05). Adding ultrasound variables to linear regression models based on bone quantity improved adjusted squared correlation coefficients from 0.65 to 0.77 (stiffness), 0.76 to 0.81 (apparent modulus), and 0.67 to 0.73 (yield stress). These results indicate that ultrasound can provide complementary (to bone quantity) information regarding mechanical behavior of cancellous bone
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High-precision method for cyclic loading of small-animal vertebrae to assess bone quality.
One potentially important bone quality characteristic is the response of bone to cyclic (repetitive) mechanical loading. In small animals, such as in rats and mice, cyclic loading experiments are particularly challenging to perform in a precise manner due to the small size of the bones and difficult-to-eliminate machine compliance. Addressing this issue, we developed a precise method for ex vivo cyclic compressive loading of isolated mouse vertebral bodies. The method has three key characteristics: 3D-printed support jigs for machining plano-parallel surfaces of the tiny vertebrae; pivotable loading platens to ensure uniform contact and loading of specimen surfaces; and specimen-specific micro-CT-based finite element analysis to measure stiffness to prescribe force levels that produce the same specified level of strain for all test specimens. To demonstrate utility, we measured fatigue life for three groups (n = 5-6 per group) of L5 vertebrae of C57BL/6J male mice, comparing our new method against two methods commonly used in the literature. We found reduced scatter of the mechanical behavior for this new method compared to the literature methods. In particular, for a controlled level of strain, the standard deviation of the measured fatigue life was up to 5-fold lower for the new method (F-ratio = 4.9; p < 0.01). The improved precision for this new method for biomechanical testing of small-animal vertebrae may help elucidate aspects of bone quality
High-precision method for cyclic loading of small-animal vertebrae to assess bone quality
One potentially important bone quality characteristic is the response of bone to cyclic (repetitive) mechanical loading. In small animals, such as in rats and mice, cyclic loading experiments are particularly challenging to perform in a precise manner due to the small size of the bones and difficult-to-eliminate machine compliance. Addressing this issue, we developed a precise method for ex vivo cyclic compressive loading of isolated mouse vertebral bodies. The method has three key characteristics: 3D-printed support jigs for machining plano-parallel surfaces of the tiny vertebrae; pivotable loading platens to ensure uniform contact and loading of specimen surfaces; and specimen-specific micro-CT-based finite element analysis to measure stiffness to prescribe force levels that produce the same specified level of strain for all test specimens. To demonstrate utility, we measured fatigue life for three groups (n = 5–6 per group) of L5 vertebrae of C57BL/6J male mice, comparing our new method against two methods commonly used in the literature. We found reduced scatter of the mechanical behavior for this new method compared to the literature methods. In particular, for a controlled level of strain, the standard deviation of the measured fatigue life was up to 5-fold lower for the new method (F-ratio = 4.9; p < 0.01). The improved precision for this new method for biomechanical testing of small-animal vertebrae may help elucidate aspects of bone quality. Keywords: Fatigue, Bone mechanics, Mouse, Vertebrae, Bone qualit
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Microstructural abnormalities are evident by histology but not HR-pQCT at the periosteal cortex of the human tibia under CVD and T2D conditions
Cortical bone microstructure deficits may increase fracture risk in individuals with cardiovascular disease and diabetes. High resolution peripheral quantitative computed tomography (HR-pQCT) enables in vivo microstructure characterization but is limited in its ability to visualize important biological features. We conducted histological analyses and HR-pQCT imaging of distal tibia bone samples from 6 donors with cardiovascular disease (CVD) and type 2 diabetes mellitus (T2D). Histology but not HR-pQCT identified previously undocumented morphopathological deficits that may contribute to cortical bone fragility. These observations may provide guidance for improved HR-pQCT microstructural characterization as well as insight into mechanisms of cortical bone degradation
Relations Between Bone Quantity, Microarchitecture, and Collagen Cross-links on Mechanics Following In Vivo Irradiation in Mice.
Humans are exposed to ionizing radiation via spaceflight or cancer radiotherapy, and exposure from radiotherapy is known to increase risk of skeletal fractures. Although irradiation can reduce trabecular bone mass, alter trabecular microarchitecture, and increase collagen cross-linking, the relative contributions of these effects to any loss of mechanical integrity remain unclear. To provide insight, while addressing both the monotonic strength and cyclic-loading fatigue life, we conducted total-body, acute, gamma-irradiation experiments on skeletally mature (17-week-old) C57BL/6J male mice (n = 84). Mice were administered doses of either 0 Gy (sham), 1 Gy (motivated by cumulative exposures from a Mars mission), or 5 Gy (motivated by clinical therapy regimens) with retrieval of the lumbar vertebrae at either a short-term (11-day) or long-term (12-week) time point after exposure. Micro-computed tomography was used to assess trabecular and cortical quantity and architecture, biochemical composition assays were used to assess collagen quality, and mechanical testing was performed to evaluate vertebral compressive strength and fatigue life. At 11 days post-exposure, 5 Gy irradiation significantly reduced trabecular mass (p < 0.001), altered microarchitecture (eg, connectivity density p < 0.001), and increased collagen cross-links (p < 0.001). Despite these changes, vertebral strength (p = 0.745) and fatigue life (p = 0.332) remained unaltered. At 12 weeks after 5 Gy exposure, the trends in trabecular bone persisted; in addition, regardless of irradiation, cortical thickness (p < 0.01) and fatigue life (p < 0.01) decreased. These results demonstrate that the highly significant effects of 5 Gy total-body irradiation on the trabecular bone morphology and collagen cross-links did not translate into detectable effects on vertebral mechanics. The only mechanical deficits observed were associated with aging. Together, these vertebral results suggest that for spaceflight, irradiation alone will likely not alter failure properties, and for radiotherapy, more investigations that include post-exposure time as a positive control and testing of both failure modalities are needed to determine the cause of increased fracture risk. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research. This article has been contributed to by US Government employees and their work is in the public domain in the USA