Browsing by Author "Amling, Michael (7005175450)"

Background. Age- and sex-specific 3D bone structure patterns in human radii and tibiae were investigated with respect to individuals' osteodensitometric status to unravel associations with site-specific fracture occurrences and underlying loading patterns. Methods. A sample of 385 patients (121 men and 264 women, age range: 23-91 years) were investigated. The patients were classified according to dual X-ray absorptiometry T-scores in three groups: control (n = 60), osteopenia (n = 160), and osteoporosis (n = 165). Bone architecture and geometry were assessed by high-resolution peripheral quantitative computed tomography of the cortical and trabecular compartments in distal radii and tibiae. Results. We found site-dependent age- and sex-related trends regarding bone architecture and geometry. Females displayed more pronounced age-related changes than males. Specifically, female radii showed both cortical and trabecular structural deterioration with aging, whereas the tibiae demonstrated exclusively cortical deterioration. The mean cortical perimeter revealed a significant age-related increase for both sexes even after adjusting for body height and weight, which suggests that periosteal expansion can be observed in both the tibia and also in the radius. Osteopenia and osteoporosis cases did not reveal higher cortical perimeters in comparison to controls. Conclusions. The tomographic assessment of bone structure further clarifies the architectural basis for increased bone fragility at distal radii and tibiae with advanced age leading to fracture predilection in females. Our findings may represent a morphological link to epidemiological data on age-dependent fracture incidences. Our data support the presence of periosteal apposition at both skeletal sites despite different loading magnitudes, and challenges the view on periosteal expansion just as a compensatory mechanism to counterbalance bone loss. © 2015 The Author.

Osteoclasts are unique cells capable of bone resorption and therefore have become a major target in osteoporosis treatment strategies. Bisphosphonates suppress bone turnover via interference with the internal enzymatic cell system of osteoclasts leading to cytoskeletal disruption. This mechanism found its clinical relevance in reducing bone resorption, stabilizing bone mass and reducing fracture risk in osteoporosis patients. However, knowledge about specific in vivo changes in osteoclast cell morphology and function is still insufficient. We examined osteoclasts in 23 paired bone biopsies from osteoporosis patients (18 males, 5 females; age: 52.6 ± 11.5. yrs) under nitrogen-containing bisphosphonate administration with a mean treatment duration of three years. Formalin-fixed, undecalcified sections were assessed by qualitative and quantitative bone histomorphometry, where the osteoclast morphology, nuclei, distribution, location as well as resorption parameters were investigated to obtain information about cell function and viability. After three years of treatment, resorption parameters decreased significantly while the number of osteoclasts remained unchanged. Out of 23 patients, nine developed previously termed "giant-osteoclasts" with increased size, numerous nuclei (>. 10 nuclei/Oc) and oftentimes detachment from the bone surface. These cells frequently had pycnotic nuclei and other morphological signs suggestive of osteoclast apoptosis. Characteristic large-sized osteoclasts were uniquely found in patients treated with nitrogen-containing bisphosphonates, thus being clearly distinguishable from giant-osteoclasts in other bone disorders such as Paget disease, secondary hyperparathyroidism or osteopetrosis. The resorption indices of large-sized osteoclasts, specifically the eroded perimeter and erosion depth, revealed significantly reduced values but not an entirely inhibited resorption capability. Bisphosphonate-osteoclasts' viability and affinity to bone seem significantly disturbed while the apoptotic process may be prolonged for a yet unknown period of time in favor of maintaining a low bone turnover. © 2013 Elsevier Inc.

Osteoclasts are unique cells capable of bone resorption and therefore have become a major target in osteoporosis treatment strategies. Bisphosphonates suppress bone turnover via interference with the internal enzymatic cell system of osteoclasts leading to cytoskeletal disruption. This mechanism found its clinical relevance in reducing bone resorption, stabilizing bone mass and reducing fracture risk in osteoporosis patients. However, knowledge about specific in vivo changes in osteoclast cell morphology and function is still insufficient. We examined osteoclasts in 23 paired bone biopsies from osteoporosis patients (18 males, 5 females; age: 52.6 ± 11.5. yrs) under nitrogen-containing bisphosphonate administration with a mean treatment duration of three years. Formalin-fixed, undecalcified sections were assessed by qualitative and quantitative bone histomorphometry, where the osteoclast morphology, nuclei, distribution, location as well as resorption parameters were investigated to obtain information about cell function and viability. After three years of treatment, resorption parameters decreased significantly while the number of osteoclasts remained unchanged. Out of 23 patients, nine developed previously termed "giant-osteoclasts" with increased size, numerous nuclei (>. 10 nuclei/Oc) and oftentimes detachment from the bone surface. These cells frequently had pycnotic nuclei and other morphological signs suggestive of osteoclast apoptosis. Characteristic large-sized osteoclasts were uniquely found in patients treated with nitrogen-containing bisphosphonates, thus being clearly distinguishable from giant-osteoclasts in other bone disorders such as Paget disease, secondary hyperparathyroidism or osteopetrosis. The resorption indices of large-sized osteoclasts, specifically the eroded perimeter and erosion depth, revealed significantly reduced values but not an entirely inhibited resorption capability. Bisphosphonate-osteoclasts' viability and affinity to bone seem significantly disturbed while the apoptotic process may be prolonged for a yet unknown period of time in favor of maintaining a low bone turnover. © 2013 Elsevier Inc.

Cement lines are known as thin peripheral boundaries of the osteons. With a thickness below 5 μm their composition of inorganic and organic compounds has been a matter of debate. Here, we hypothesized that cement lines become hypermineralized and their degree of mineralization is not constant but related to the tissue age of the osteon. Therefore, we analyzed the calcium content of osteons and their corresponding cement lines in a range of different tissue ages reflected by osteonal mineralization levels in femoral cortical bone of both postmenopausal women with osteoporosis and bisphosphonate-treated cases. Quantitative backscattered electron imaging (qBEI) showed that cement lines are hypermineralized entities with consistently higher calcium content than their corresponding osteons (mean calcium content: 29.46 ± 0.80 vs. 26.62 ± 1.11 wt%; p < 0.001). Micro-Raman spectroscopy complemented the qBEI data by showing a significantly higher phosphate/amide I ratio in the cement lines compared to the osteonal bone (8.78 ± 0.66 vs. 6.33 ± 0.58, p < 0.001), which was both due to an increased phosphate peak and a reduced amide I peak in cement lines. A clear positive correlation of cement line mineralization and the mineralization of the osteon was observed (r = 0.839, p = 0.003). However, the magnitude of the difference between cement line and osteonal calcium content decreased with increased osteonal calcium content (r = −0.709, p < 0.001), suggesting diverging mineralization dynamics in these osseous entities. The number of mineralized osteocyte lacunae per osteon bone area correlated positively with both osteonal and cement line calcium content (p < 0.01). The degree of mineralization of cement lines may represent another tissue-age related phenomenon, given that it strongly relates to the osteonal mineralization level. Understanding of the cement lines' mineralization and their changes in aging and disease states is important for predicting crack propagation pathways and fracture resistance mechanisms in human cortical bone. © 2018 Elsevier Inc.

Cement lines are known as thin peripheral boundaries of the osteons. With a thickness below 5 μm their composition of inorganic and organic compounds has been a matter of debate. Here, we hypothesized that cement lines become hypermineralized and their degree of mineralization is not constant but related to the tissue age of the osteon. Therefore, we analyzed the calcium content of osteons and their corresponding cement lines in a range of different tissue ages reflected by osteonal mineralization levels in femoral cortical bone of both postmenopausal women with osteoporosis and bisphosphonate-treated cases. Quantitative backscattered electron imaging (qBEI) showed that cement lines are hypermineralized entities with consistently higher calcium content than their corresponding osteons (mean calcium content: 29.46 ± 0.80 vs. 26.62 ± 1.11 wt%; p < 0.001). Micro-Raman spectroscopy complemented the qBEI data by showing a significantly higher phosphate/amide I ratio in the cement lines compared to the osteonal bone (8.78 ± 0.66 vs. 6.33 ± 0.58, p < 0.001), which was both due to an increased phosphate peak and a reduced amide I peak in cement lines. A clear positive correlation of cement line mineralization and the mineralization of the osteon was observed (r = 0.839, p = 0.003). However, the magnitude of the difference between cement line and osteonal calcium content decreased with increased osteonal calcium content (r = −0.709, p < 0.001), suggesting diverging mineralization dynamics in these osseous entities. The number of mineralized osteocyte lacunae per osteon bone area correlated positively with both osteonal and cement line calcium content (p < 0.01). The degree of mineralization of cement lines may represent another tissue-age related phenomenon, given that it strongly relates to the osteonal mineralization level. Understanding of the cement lines' mineralization and their changes in aging and disease states is important for predicting crack propagation pathways and fracture resistance mechanisms in human cortical bone. © 2018 Elsevier Inc.

Type 2 diabetes mellitus (T2DM), a metabolic disease on the rise, is associated with substantial increase in bone fracture risk. Because individuals with T2DM have normal or high bone mineral density (BMD), osteodensitometric measurements of BMD do not predict fracture risk with T2DM. Here, we aim to identify the underlying mechanism of the diabetes-induced fracture risk using a high-resolution multi-scale analysis of human cortical bone with special emphasis on osseous cellular activity. Specifically, we show increased cortical porosity in a subgroup of T2DM individuals accompanied by changed mineralization patterns and glycoxidative damage to bone protein, caused by non-enzymatic glycation of bone by reducing sugar. Furthermore, the high porosity T2DM subgroup presents with higher regional mineralization heterogeneity and lower mineral maturity, whereas in the T2DM subgroup regional higher mineral-to-matrix ratio was observed. Both T2DM groups show significantly higher carboxymethyl-lysine accumulation. Our results show a dimorphic pattern of cortical bone reorganization in individuals afflicted with T2DM and hence provide new insight into the diabetic bone disease leading to increased fracture risk. © 2020 Elsevier Inc.

Type 2 diabetes mellitus (T2DM), a metabolic disease on the rise, is associated with substantial increase in bone fracture risk. Because individuals with T2DM have normal or high bone mineral density (BMD), osteodensitometric measurements of BMD do not predict fracture risk with T2DM. Here, we aim to identify the underlying mechanism of the diabetes-induced fracture risk using a high-resolution multi-scale analysis of human cortical bone with special emphasis on osseous cellular activity. Specifically, we show increased cortical porosity in a subgroup of T2DM individuals accompanied by changed mineralization patterns and glycoxidative damage to bone protein, caused by non-enzymatic glycation of bone by reducing sugar. Furthermore, the high porosity T2DM subgroup presents with higher regional mineralization heterogeneity and lower mineral maturity, whereas in the T2DM subgroup regional higher mineral-to-matrix ratio was observed. Both T2DM groups show significantly higher carboxymethyl-lysine accumulation. Our results show a dimorphic pattern of cortical bone reorganization in individuals afflicted with T2DM and hence provide new insight into the diabetic bone disease leading to increased fracture risk. © 2020 Elsevier Inc.

Background: The osteocytic lacunar network is considered to be an integral player in the regulation of bone homeostasis, and reduction in osteocytes is associated with reduced bone strength. Here, we analyzed site-specific patterns in osteocyte characteristics and matrix composition in the cortical compartment of the femoral neck to reveal the structural basis of its fragility. Methods: Cross-sections of the human femoral neck - one of the most common fracture sites - were acquired from 12 female cadavers (age 34–86 years) and analyzed with backscattered scanning electron microscopy and high-resolution micro-computed tomography (μ-CT). The 2D/3D density and size of the osteocyte lacunae as well as bone mineral density distribution (BMDD) were measured in two regions subject to different biomechanical loads in vivo: the inferomedial (medial) region (habitually highly loaded in compression) and the superolateral (lateral) region (lower habitual loading intensity). Using quantitative polarized light microscopy, collagen fiber orientation was quantified in these two regions, accordingly. Results: In 2D measurements, the inferomedial region displayed lower mineralization heterogeneity, 19% higher osteocyte lacunar density (p = 0.005), but equal lacunar size compared to the superolateral region. 3D measurements confirmed a significantly higher osteocyte lacunar density in the inferomedial region (p = 0.015). Osteocyte lacunar density decreased in aged individuals, and inter-site differences were reduced. Site-specific osteocyte characteristics were not accompanied by changes in collagen fiber orientation. Conclusions: Since osteocyte characteristics may provide valuable insights into bone mechanical competence, the variations in osteocyte properties might reflect the increased fracture susceptibility of the superolateral neck. © 2018

Background: The osteocytic lacunar network is considered to be an integral player in the regulation of bone homeostasis, and reduction in osteocytes is associated with reduced bone strength. Here, we analyzed site-specific patterns in osteocyte characteristics and matrix composition in the cortical compartment of the femoral neck to reveal the structural basis of its fragility. Methods: Cross-sections of the human femoral neck - one of the most common fracture sites - were acquired from 12 female cadavers (age 34–86 years) and analyzed with backscattered scanning electron microscopy and high-resolution micro-computed tomography (μ-CT). The 2D/3D density and size of the osteocyte lacunae as well as bone mineral density distribution (BMDD) were measured in two regions subject to different biomechanical loads in vivo: the inferomedial (medial) region (habitually highly loaded in compression) and the superolateral (lateral) region (lower habitual loading intensity). Using quantitative polarized light microscopy, collagen fiber orientation was quantified in these two regions, accordingly. Results: In 2D measurements, the inferomedial region displayed lower mineralization heterogeneity, 19% higher osteocyte lacunar density (p = 0.005), but equal lacunar size compared to the superolateral region. 3D measurements confirmed a significantly higher osteocyte lacunar density in the inferomedial region (p = 0.015). Osteocyte lacunar density decreased in aged individuals, and inter-site differences were reduced. Site-specific osteocyte characteristics were not accompanied by changes in collagen fiber orientation. Conclusions: Since osteocyte characteristics may provide valuable insights into bone mechanical competence, the variations in osteocyte properties might reflect the increased fracture susceptibility of the superolateral neck. © 2018

Immobilization as a result of long-term bed rest can lead to gradual bone loss. Because of their distribution throughout the bone matrix and remarkable interconnectivity, osteocytes represent the major mechanosensors in bone and translate mechanical into biochemical signals controlling bone remodeling. To test whether immobilization affects the characteristics of the osteocyte network in human cortical bone, femoral diaphyseal bone specimens were analyzed in immobilized female individuals and compared with age-matched postmenopausal individuals with primary osteoporosis. Premenopausal and postmenopausal healthy individuals served as control groups. Cortical porosity, osteocyte number and lacunar area, the frequency of hypermineralized lacunae, as well as cortical bone calcium content (CaMean) were assessed using bone histomorphometry and quantitative backscattered electron imaging (qBEI). Bone matrix properties were further analyzed by Fourier transform infrared spectroscopy (FTIR). In the immobilization group, cortical porosity was significantly higher, and qBEI revealed a trend toward higher matrix mineralization compared with osteoporotic individuals. Osteocyte density and canalicular density showed a declining rate from premenopausal toward healthy postmenopausal and osteoporotic individuals with peculiar reductions in the immobilization group, whereas the number of hypermineralized lacunae accumulated inversely. In conclusion, reduced osteocyte density and impaired connectivity during immobilization are associated with a specific bone loss pattern, reflecting a phenotype clearly distinguishable from postmenopausal osteoporosis. Immobilization periods may lead to a loss of survival signals for osteocytes, provoking bone loss that is even higher than in osteoporosis states, whereas osteocytic osteolysis remains absent. © 2020 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research. © 2020 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research

In this study we analyzed the trabecular bone micro-architecture in the inferomedial and superolateral subregions of the femoral neck in a group with hip fractures and a control group of elderly women, with aim to clarify the micro-structural basis of bone fragility.Proximal femora from 29 Caucasian female cadavers were collected at Institute of Forensic Medicine in Belgrade (15 women with hip fracture: age 79.5. ±. 8.5. yrs.; and 14 women without hip fractures: age 74.1. ±. 9.3. yrs.). The femoral neck section was scanned in dry conditions using a micro-computed tomography (Scanco μCT 40), at 70. kV, 114. μA, 300. ms integration time, 36. μm resolution, isotropic, 1024. ×. 1024. pixels per slice, automatically evaluating trabecular micro-architecture using the built-in program of the micro-CT with direct 3D morphometry. The samples were foam padded to avoid any movement artifacts during scanning.Analysis of the neck section in the fracture group compared to the control cases demonstrated significantly lower bone volume fraction (mean: 6.3% vs. 11.2%, p=0.002), lower connectivity density (0.33/mm 3 vs. 0.74/mm 3, p=0.019) and higher trabecular separation (0.87mm vs. 0.83mm, p=0.030). Division into the superolateral and inferomedial regions of interest revealed that the superolateral neck displayed even more differences in micro-architectural properties between the fracture and non-fracture groups. Namely, while in the inferomedial neck only bone volume fraction and degree of anisotropy displayed significant inter-group variability (lower BV/TV with higher degree of anisotropy in the fracture group), in the superolateral neck almost all parameters were different between the fracture cases and the controls, where the fracture group showed a lower trabecular bone volume fraction (3.6% vs. 8.2%, p=0.001), lower connectivity (0.21 vs. 0.63/mm 3, p=0.008), more rod like trabecular structure (SMI: 2.94 vs. 2.62, p=0.049), higher separation and the thinned trabeculae (Tb.Sp: 0.89 vs. 0.85mm, p=0.013; Tb.Th: 0.17 vs. 0.20mm, p=0.05). In addition, after adjusting for the effects of BV/TV, the majority of differences disappeared, demonstrating that the bone loss manifests itself via the changes in micro-architectural parameters: trabecular thinning, rising the spacing between individual trabeculae, reducing trabecular connectivity and accentuating trabecular perforations leading to predominance of rod-like trabecular elements.Preferential impairment of the superolateral neck trabecular structure and organization in women with hip fracture reveals the region-dependent micro-structural basis of bone fragility in elderly women. © 2011 Elsevier Inc.

In this study we analyzed the trabecular bone micro-architecture in the inferomedial and superolateral subregions of the femoral neck in a group with hip fractures and a control group of elderly women, with aim to clarify the micro-structural basis of bone fragility.Proximal femora from 29 Caucasian female cadavers were collected at Institute of Forensic Medicine in Belgrade (15 women with hip fracture: age 79.5. ±. 8.5. yrs.; and 14 women without hip fractures: age 74.1. ±. 9.3. yrs.). The femoral neck section was scanned in dry conditions using a micro-computed tomography (Scanco μCT 40), at 70. kV, 114. μA, 300. ms integration time, 36. μm resolution, isotropic, 1024. ×. 1024. pixels per slice, automatically evaluating trabecular micro-architecture using the built-in program of the micro-CT with direct 3D morphometry. The samples were foam padded to avoid any movement artifacts during scanning.Analysis of the neck section in the fracture group compared to the control cases demonstrated significantly lower bone volume fraction (mean: 6.3% vs. 11.2%, p=0.002), lower connectivity density (0.33/mm 3 vs. 0.74/mm 3, p=0.019) and higher trabecular separation (0.87mm vs. 0.83mm, p=0.030). Division into the superolateral and inferomedial regions of interest revealed that the superolateral neck displayed even more differences in micro-architectural properties between the fracture and non-fracture groups. Namely, while in the inferomedial neck only bone volume fraction and degree of anisotropy displayed significant inter-group variability (lower BV/TV with higher degree of anisotropy in the fracture group), in the superolateral neck almost all parameters were different between the fracture cases and the controls, where the fracture group showed a lower trabecular bone volume fraction (3.6% vs. 8.2%, p=0.001), lower connectivity (0.21 vs. 0.63/mm 3, p=0.008), more rod like trabecular structure (SMI: 2.94 vs. 2.62, p=0.049), higher separation and the thinned trabeculae (Tb.Sp: 0.89 vs. 0.85mm, p=0.013; Tb.Th: 0.17 vs. 0.20mm, p=0.05). In addition, after adjusting for the effects of BV/TV, the majority of differences disappeared, demonstrating that the bone loss manifests itself via the changes in micro-architectural parameters: trabecular thinning, rising the spacing between individual trabeculae, reducing trabecular connectivity and accentuating trabecular perforations leading to predominance of rod-like trabecular elements.Preferential impairment of the superolateral neck trabecular structure and organization in women with hip fracture reveals the region-dependent micro-structural basis of bone fragility in elderly women. © 2011 Elsevier Inc.

Although the concept of the occlusal load transfer through the facial skeleton along the buttresses has been extensively studied, there has been no study to link microarchitecture of the mid-facial bones to the occlusal load distribution. The aim of this study was to analyze micro-structural properties of the mid-facial bones in relation to occlusal stress. The study was performed by combining the three-dimensional finite element analysis (3D FEA) and micro-computed tomography analysis (micro-CT). Clenching was simulated on the computer model of the adult male human skull which was also used as a source of bone specimens. After the FEA was run, stress was measured at the specific sites in cortical shell and trabecular bone of the model along and between the buttresses. From the corresponding sites on the skull, twenty-five cortical and thirteen cancellous bone specimens were harvested. The specimens were classified into high stress or low stress group based on the stress levels measured via the FEA. Micro-architecture of each specimen was assessed by micro-CT. In the high stress group, cortical bone showed a tendency toward greater thickness and density, lower porosity, and greater pore separation. Stress-related differences in microstructure between the groups were more pronounced in trabecular bone, which showed significantly greater bone volume fraction (BV/TV) and trabecular thickness (Tb.Th) in the high stress group. Our results suggest that the mid-facial bones in the adult dentate male skull exhibit regional variations in cortical and trabecular bone micro-architecture that could be a consequence of different occlusal stress. © 2014 Elsevier Inc.

Although the concept of the occlusal load transfer through the facial skeleton along the buttresses has been extensively studied, there has been no study to link microarchitecture of the mid-facial bones to the occlusal load distribution. The aim of this study was to analyze micro-structural properties of the mid-facial bones in relation to occlusal stress. The study was performed by combining the three-dimensional finite element analysis (3D FEA) and micro-computed tomography analysis (micro-CT). Clenching was simulated on the computer model of the adult male human skull which was also used as a source of bone specimens. After the FEA was run, stress was measured at the specific sites in cortical shell and trabecular bone of the model along and between the buttresses. From the corresponding sites on the skull, twenty-five cortical and thirteen cancellous bone specimens were harvested. The specimens were classified into high stress or low stress group based on the stress levels measured via the FEA. Micro-architecture of each specimen was assessed by micro-CT. In the high stress group, cortical bone showed a tendency toward greater thickness and density, lower porosity, and greater pore separation. Stress-related differences in microstructure between the groups were more pronounced in trabecular bone, which showed significantly greater bone volume fraction (BV/TV) and trabecular thickness (Tb.Th) in the high stress group. Our results suggest that the mid-facial bones in the adult dentate male skull exhibit regional variations in cortical and trabecular bone micro-architecture that could be a consequence of different occlusal stress. © 2014 Elsevier Inc.

Skeletal growth, modeling, and remodeling are regulated by various molecules, one of them being the recently identified osteoanabolic factor WNT1. We have previously reported that WNT1 transcriptionally activates the expression of Omd, encoding Osteomodulin (OMD), in a murine mesenchymal cell line, which potentially explained the skeletal fragility of mice with mutational WNT1 inactivation, since OMD has been shown to regulate type I collagen fibril formation in vitro. In this study we confirmed the strong induction of Omd expression in a genome-wide expression analysis of transfected cells, and we obtained further evidence for Omd being a direct target gene of WNT1. To assess the in vivo relevance of this regulation, we crossed Omd-deficient mice with a mouse line harboring an inducible, osteoblast-specific Wnt1 transgene. After induction of Wnt1 expression for 1 or 3 weeks, the osteoanabolic potency of WNT1 was not impaired despite the Omd deficiency. Since current knowledge regarding the in vivo physiological function of OMD is limited, we next focused on skeletal phenotyping of wild-type and Omd-deficient littermates, in the absence of a Wnt1 transgene. Here we did not observe an impact of Omd deficiency on trabecular bone parameters by histomorphometry and μCT either. Importantly, however, male and female Omd-deficient mice at the ages of 12 and 24 weeks displayed a slender bone phenotype with significantly smaller long bones in the transversal dimension, while the longitudinal bone growth remained unaffected. Although mechanical testing revealed no significant changes explained by impaired bone material properties, atomic force microscopy of the femoral bone surface of Omd-deficient mice revealed moderate changes at the nanostructural level, indicating altered regulation of collagen fibril formation and aggregation. Taken together, our data demonstrate that, although OMD is dispensable for the osteoanabolic effect of WNT1, its deficiency in mice specifically modulates transversal cortical bone morphology. © The Author(s) 2024.

Objectives: Parallel with body growth and development, bone structure in non-adults is reorganized to achieve the particular design observed in mature individuals. We traced the changes in three-dimensional trabecular microarchitectural design during the phases of locomotor maturation to clarify how human bone adapts to mechanical demands. Materials and Methods: Micro-CT was performed on biomechanically-relevant subregions of the proximal femur (medial, intermediate and lateral neck regions, intertrochanteric region, metaphyseal region) from early postnatal period to late childhood. Results: Developmental patterns of trabecular microarchitecture showed that gestationally overproduced bone present at birth underwent the most dramatic reduction during the first year, followed by a reversing trend in some of the quantitative parameters (e.g., bone volume fraction, trabecular anisotropy). Certain regional anisotropy already present at birth is further accentuated into the childhood suggesting an adaptation to differential loading environments. Trabecular eccentricity in the femoral neck was particularly accentuated during childhood, giving the medial neck—the site mostly loaded in walking—superior microarchitectural design (high bone volume fraction and anisotropy, the earliest appearance and predominance of plate- and honeycomb-shaped trabeculae). Discussion: While providing quantitative data on how bone microarchitecture adapts to increasing mechanical demands occurring during the phases of locomotor maturation, the study reveals how regional anisotropy develops in the proximal femur to ensure a functional and competent bone structure. Decomposing the region-specific patterns of bone mass accrual is important in understanding skeletal adaptations to bipedalism, as well for understanding why fractures often occur location-dependent, both in pediatric and elderly individuals. © 2017 Wiley Periodicals, Inc.

Objectives: Parallel with body growth and development, bone structure in non-adults is reorganized to achieve the particular design observed in mature individuals. We traced the changes in three-dimensional trabecular microarchitectural design during the phases of locomotor maturation to clarify how human bone adapts to mechanical demands. Materials and Methods: Micro-CT was performed on biomechanically-relevant subregions of the proximal femur (medial, intermediate and lateral neck regions, intertrochanteric region, metaphyseal region) from early postnatal period to late childhood. Results: Developmental patterns of trabecular microarchitecture showed that gestationally overproduced bone present at birth underwent the most dramatic reduction during the first year, followed by a reversing trend in some of the quantitative parameters (e.g., bone volume fraction, trabecular anisotropy). Certain regional anisotropy already present at birth is further accentuated into the childhood suggesting an adaptation to differential loading environments. Trabecular eccentricity in the femoral neck was particularly accentuated during childhood, giving the medial neck—the site mostly loaded in walking—superior microarchitectural design (high bone volume fraction and anisotropy, the earliest appearance and predominance of plate- and honeycomb-shaped trabeculae). Discussion: While providing quantitative data on how bone microarchitecture adapts to increasing mechanical demands occurring during the phases of locomotor maturation, the study reveals how regional anisotropy develops in the proximal femur to ensure a functional and competent bone structure. Decomposing the region-specific patterns of bone mass accrual is important in understanding skeletal adaptations to bipedalism, as well for understanding why fractures often occur location-dependent, both in pediatric and elderly individuals. © 2017 Wiley Periodicals, Inc.

Background: Currently, bone densitometry fails to identify nearly half of those elderly patients at immediate fracture risk. To improve clinical assessment of vertebral fracture risk, we aimed to determine how the DXA-based 2D parameter Trabecular Bone Score (TBS) relates to subregional variability in 3D trabecular microstructure in young and elderly women compared to aBMD. Methods: T12 vertebrae from 29 women (11 young: 32 ± 6 years, 18 aged: 71 ± 5 years) were DXA-scanned ex vivo in anterior-posterior (AP) and lateral projection providing vertebral aBMD and TBS. Additionally, aBMD and TBS were measured for three horizontal (superior, mid-horizontal, inferior) and three vertical subregions (anterior, mid-vertical, posterior) and related to 3D microstructure indices, i.e. bone volume per tissue volume (BV/TV), trabecular number and thickness (Tb.N, Tb.Th), based on HRpQCT. Results: Subregional high-resolution tomography showed significant differences in trabecular parameters for both age groups: In horizontal subregions, BV/TV was lowest superiorly, Tb.Th was highest mid-horizontally, and Tb.N was lowest mid-horizontally and highest inferiorly. Correspondingly, aBMD varied between horizontal subregions, with differences depending on projection direction. TBS varied only in lateral projections of the aged group, with lower values for the mid-horizontal subregion. In vertical subregions, BV/TV, Tb.N, and aBMD were highest posteriorly for both groups. TBS did not differ between vertical subregions. Regression analysis showed aBMD as a predictor explained more of the variance in subregional 3D microstructure compared to TBS. Stepwise multi-regression analysis revealed only three combinations of subregion, projection, and group where aBMD and TBS were both significant predictors. Conclusions: Subregional aBMD reflects variations in trabecular bone microstructure better than subregional TBS for trisected regions. Specifically, lateral aBMD identifies microstructural heterogeneities independent of age and may improve prediction of vertebral strength and susceptibility to specific fracture types. © 2019 Elsevier Inc.

Background: Currently, bone densitometry fails to identify nearly half of those elderly patients at immediate fracture risk. To improve clinical assessment of vertebral fracture risk, we aimed to determine how the DXA-based 2D parameter Trabecular Bone Score (TBS) relates to subregional variability in 3D trabecular microstructure in young and elderly women compared to aBMD. Methods: T12 vertebrae from 29 women (11 young: 32 ± 6 years, 18 aged: 71 ± 5 years) were DXA-scanned ex vivo in anterior-posterior (AP) and lateral projection providing vertebral aBMD and TBS. Additionally, aBMD and TBS were measured for three horizontal (superior, mid-horizontal, inferior) and three vertical subregions (anterior, mid-vertical, posterior) and related to 3D microstructure indices, i.e. bone volume per tissue volume (BV/TV), trabecular number and thickness (Tb.N, Tb.Th), based on HRpQCT. Results: Subregional high-resolution tomography showed significant differences in trabecular parameters for both age groups: In horizontal subregions, BV/TV was lowest superiorly, Tb.Th was highest mid-horizontally, and Tb.N was lowest mid-horizontally and highest inferiorly. Correspondingly, aBMD varied between horizontal subregions, with differences depending on projection direction. TBS varied only in lateral projections of the aged group, with lower values for the mid-horizontal subregion. In vertical subregions, BV/TV, Tb.N, and aBMD were highest posteriorly for both groups. TBS did not differ between vertical subregions. Regression analysis showed aBMD as a predictor explained more of the variance in subregional 3D microstructure compared to TBS. Stepwise multi-regression analysis revealed only three combinations of subregion, projection, and group where aBMD and TBS were both significant predictors. Conclusions: Subregional aBMD reflects variations in trabecular bone microstructure better than subregional TBS for trisected regions. Specifically, lateral aBMD identifies microstructural heterogeneities independent of age and may improve prediction of vertebral strength and susceptibility to specific fracture types. © 2019 Elsevier Inc.