Age-Related Changes in Femoral Head Trabecular Microarchitecture.
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ABSTRACT:
SUBMITTER: Greenwood C
PROVIDER: S-EPMC6284768 | biostudies-other | 2018 Dec
REPOSITORIES: biostudies-other
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Project description:PurposeTo evaluate the normal aging effects on trabecular meshwork (TM) parameters using Fourier domain anterior segment optical coherence tomography (ASOCT) images.Patients and methodsOne eye from 45 participants with open angles was imaged. Two independent readers measured TM area, TM length, and area and length of the TM interface shadow from 3 age groups (18-40, 41-60, and 61-80). Measurements were compared using stepwise regression analysis.ResultsThe average TM parameters were 0.0487 (± 0.0092) mm(2) for TM area, 0.5502 (± 0.1033) mm for TM length, 0.1623 (± 0.341) mm(2) for TM interface shadow area, and 0.7755 (± 0.1574) mm for TM interface shadow length. Interobserver reproducibility coefficients ranged from 0.45 (TM length) to 0.82 (TM area). TM area and length were not correlated with age. While the TM interface shadow length did not correlate with age, the TM interface shadow area increased with age. Race, sex, intraocular pressure, and gonioscopy score were not correlated with any TM parameters.ConclusionAlthough the TM measurements were not correlated with age, the TM interface shadow area increased with age. Further study is required to determine whether there is any relationship between the age-related ASOCT findings of the TM interface shadow area and physiologic function.
| S-EPMC3791583 | biostudies-literature
Project description:The mechanism behind osteonecrosis of the femoral head (ONFH) remains unclear. The aim of this study was to explore the pathogenesis of ONFH from a biomechanical standpoint to provide a theoretical basis for improved treatments. We compared the bone structure of fractured femoral heads with that of necrotic femoral heads by Micro-CT scanning and histological evaluation. In addition, we compared the biomechanical properties of each zone in fractured femoral heads with those in necrotic femoral heads by using biomechanical tests. Compared with fractured femoral heads, bone microarchitecture and bone morphometry in necrotic zone and sclerotic zone of necrotic femoral heads have altered markedly. In addition, the biomechanical properties of the necrotic zone in femoral heads weaken markedly, while those of the sclerotic zone strengthen. We hypothesize that discordance between bone structure and function of the femoral head may be involved in the pathogenesis of ONFH and that more attention should be paid to the prevention and treatment of such discordance.
| S-EPMC5645321 | biostudies-literature
Project description:BackgroundSciuromorpha (squirrels and close relatives) are diverse in terms of body size and locomotor behavior. Individual species are specialized to perform climbing, gliding or digging behavior, the latter being the result of multiple independent evolutionary acquisitions. Each lifestyle involves characteristic loading patterns acting on the bones of sciuromorphs. Trabecular bone, as part of the bone inner structure, adapts to such loading patterns. This network of thin bony struts is subject to bone modeling, and therefore reflects habitual loading throughout lifetime. The present study investigates the effect of body size and lifestyle on trabecular structure in Sciuromorpha.MethodsBased upon high-resolution computed tomography scans, the femoral head 3D inner microstructure of 69 sciuromorph species was analyzed. Species were assigned to one of the following lifestyle categories: arboreal, aerial, fossorial and semifossorial. A cubic volume of interest was selected in the center of each femoral head and analyzed by extraction of various parameters that characterize trabecular architecture (degree of anisotropy, bone volume fraction, connectivity density, trabecular thickness, trabecular separation, bone surface density and main trabecular orientation). Our analysis included evaluation of the allometric signals and lifestyle-related adaptation in the trabecular parameters.ResultsWe show that bone surface density, bone volume fraction, and connectivity density are subject to positive allometry, and degree of anisotropy, trabecular thickness, and trabecular separation to negative allometry. The parameters connectivity density, bone surface density, trabecular thickness, and trabecular separation show functional signals which are related to locomotor behavior. Aerial species are distinguished from fossorial ones by a higher trabecular thickness, lower connectivity density and lower bone surface density. Arboreal species are distinguished from semifossorial ones by a higher trabecular separation.ConclusionThis study on sciuromorph trabeculae supplements the few non-primate studies on lifestyle-related functional adaptation of trabecular bone. We show that the architecture of the femoral head trabeculae in Sciuromorpha correlates with body mass and locomotor habits. Our findings provide a new basis for experimental research focused on functional significance of bone inner microstructure.
| S-EPMC5954450 | biostudies-literature
Project description:Ageing of the skeleton is characterised by decreased bone mineral density, reduced strength, and increased risk of fracture. Although it is known that these changes are determined by the activities of bone cells through the processes of bone modelling and remodelling, details of the molecular mechanisms that underlie age-related changes in bone are still missing. Here, we analysed age-related changes in bone microarchitecture along with global gene expression in samples obtained from patients with osteoarthritis (OA). We hypothesised that changes would be evident in both microarchitecture and gene expression and aimed to identify novel molecular mechanisms that underlie ageing processes in bone. Samples of femoral head and neck were obtained from patients undergoing hip arthroplasty for OA, who were either ≤60 years or ≥70 years of age. Bone microarchitecture was analysed in cores of trabecular bone from the femoral head (17 from the younger group and 18 from the older), and cortical bone from the femoral neck (25 younger/22 older), using a Skyscan 1172 microCT scanner (Bruker). Gene expression was compared between the two age groups in 20 trabecular samples from each group, and 10 cortical samples from each group, using Clariom S Human microarrays (ThermoFisher Scientific). We found no significant changes between the two age groups in indices of trabecular or cortical bone microarchitecture. Gene expression analysis identified seven genes that had higher expression in the older group, including the transcription factor EGR1 and the glucose transporter SLC2A3 (GLUT3), and 21 differentially expressed genes in cortical bone samples (P<0.05, fold change>2). However, none of the comparisons of gene expression had false discovery rate-adjusted P<0.1. In contrast to our working hypothesis, we found only minor differences in gene expression and no differences in bone microarchitecture between the two age-groups. It is possible that pathological processes related to OA provide protection against age-related changes in bone. Our study suggests that in patients with OA, the bone properties measured here in femoral head and neck do not deteriorate significantly from the sixth to the eighth decade of life.
| S-EPMC7292911 | biostudies-literature
Project description:BackgroundGlucocorticoid usage and alcohol abuse are the most widely accepted risk factors for nontraumatic osteonecrosis of femoral head (ONFH). Despite distinct etiologies between glucocorticoid-associated ONFH (GONFH) and alcohol-associated ONFH (AONFH), little is known about the differences of the microarchitectural and histomorphologic characteristics between these subtypes of ONFH.PurposesTo investigate bone microarchitecture, bone remodeling activity and histomorphology characteristics of different regions in femoral heads between GONFH and AONFH.MethodsFrom September 2015 to October 2020, 85 patients diagnosed with GONFH and AONFH were recruited. Femoral heads were obtained after total hip replacement. Femoral head specimens were obtained from 42 patients (50 hips) with GONFH and 43 patients (50 hips) with AONFH. Micro-CT was utilized to assess the microstructure of 9 regions of interest (ROIs) in the femoral head. Along the supero-inferior orientation, the femoral head was divided into necrotic region, reactive interface, and normal region; along the medio-lateral orientation, the femoral head was divided into medial region, central region and lateral region. Decalcified and undecalcified bone histology was subsequently performed to evaluate histopathological alterations and bone remodeling levels.ResultsIn the necrotic region, most of the microarchitectural parameters did not differ significantly between GONFH and AONFH, whereas both the reactive interface and normal region revealed a less sclerotic microarchitecture but a higher bone remodeling level in GONFH than AONFH. Despite similar necrotic pathological manifestations, subchondral trabecular microfracture in the necrotic region was more severe and vasculature of the reactive interface was more abundant in GONFH.ConclusionsGONFH and AONFH shared similar microarchitecture and histopathological features in the necrotic region, while GONFH exhibited a less sclerotic microarchitecture and a more active bone metabolic status in both the reactive interface and normal region. These differences between GONFH and AONFH in bone microarchitectural and histopathological characteristics might contribute to the development of disease-modifying prevention strategies and treatments for ONFH, taking into etiologies.
| S-EPMC10031038 | biostudies-literature
Project description:BackgroundAortic stiffness as measured by carotid-femoral pulse wave velocity (cfPWV) is known to depend on blood pressure (BP), and this dependency may change with age. Therefore, the hydrostatic BP gradient resulting from a change in body posture may elicit a cfPWV change that is age-dependent. We aimed to analyze the relationship between BP gradient-induced by head-up body tilting-and related changes in cfPWV in individuals of varying age.MethodscfPWV and other hemodynamic parameters were measured in 30 healthy individuals at a head-up tilt of 0° (supine), 30°, and 60°. At each angle, the PWV gradient and resulting cfPWV were also estimated (predicted) by assuming a global nonlinear, exponential, pressure-diameter relationship characterized by a constant β0, and taking into account that (diastolic) foot-to-foot cfPWV acutely depends on diastolic BP.ResultscfPWV significantly increased upon body tilting (8.0 ± 2.0 m/s supine, 9.1 ± 2.6 m/s at 30°, 9.5 ± 3.2 m/s at 60°, P for trend <0.01); a positive trend was also observed for heart rate (HR; P < 0.01). When the observed, tilt-induced cfPWV change measured by applanation tonometry was compared with that predicted from the estimated BP hydrostatic gradient, the difference in observed-vs.-predicted PWV change increased nonlinearly as a function of age (R2 for quadratic trend = 0.38, P < 0.01, P vs. linear = 0.04). This result was unaffected by HR tilt-related variations (R2 for quadratic trend = 0.37, P < 0.01, P vs. linear = 0.04).ConclusionsUnder a hydrostatic pressure gradient, the pulse wave traveling along the aorta undergoes an age-related, nonlinear PWV increase exceeding the increase predicted from BP dependency.
| S-EPMC7814224 | biostudies-literature
Project description:Our understanding of the genetic control of bone strength has relied mainly on estimates of bone mineral density. Here we have mapped genetic factors that influence femoral and tibial microarchitecture using high-resolution x-ray computed tomography (8-μm isotropic voxels) across a family of 61 BXD strains of mice, roughly 10 isogenic cases per strain and balanced by sex. We computed heritabilities for 25 cortical and trabecular traits. Males and females have well-matched heritabilities, ranging from 0.25 to 0.75. We mapped 16 genetic loci most of which were detected only in females. There is also a bias in favor of loci that control cortical rather than trabecular bone. To evaluate candidate genes, we combined well-established gene ontologies with bone transcriptome data to compute bone-enrichment scores for all protein-coding genes. We aligned candidates with those of human genome-wide association studies. A subset of 50 strong candidates fell into three categories: (1) experimentally validated genes already known to modulate bone function (Adamts4, Ddr2, Darc, Adam12, Fkbp10, E2f6, Adam17, Grem2, Ifi204); (2) candidates without any experimentally validated function in bone (eg, Greb1, Ifi202b), but linked to skeletal phenotypes in human cohorts; and (3) candidates that have high bone-enrichment scores, but for which there is not yet any functional link to bone biology or skeletal system disease (including Ifi202b, Ly9, Ifi205, Mgmt, F2rl1, Iqgap2). Our results highlight contrasting genetic architecture between sexes and among major bone compartments. The alignment of murine and human data facilitates function analysis and should prove of value for preclinical testing of molecular control of bone structure. © 2019 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.
| S-EPMC6894729 | biostudies-literature
Project description:Individuals with diabetes mellitus type 2 (T2DM) have an increased risk of hip fracture, especially if vascular complications are present. However, microstructural origins of increased bone fragility in T2DM are still controversial. DXA measurement of the contralateral hip and three-dimensional microCT analyses of femoral neck trabecular microarchitecture were performed in 32 individuals (26 women and 6 men, 78 ± 7 years). The specimens were divided to two groups: T2DM individuals with hip fracture (DMFx, n = 18) and healthy controls (CTL, n = 14). DMFx group consisted of individuals with vascular complications (DMFx_VD, n = 8) and those without vascular complications (DMFx_NVD, n = 10). T-score was significantly lower in DMFx_VD and DMFx_NVD than in controls (p < 0.001). BV/TV, Tb.N, Tb.Sp, SMI, and FD varied among DMFx_NVD, DMFx_VD, and CTL groups (p = 0.023, p = 0.004, p = 0.008, p = 0.001, p = 0.007, respectively). Specifically, BV/TV of DMFx_VD was significantly lower than that of DMFx_NVD group (p = 0.020); DMFx_NVD group had higher Tb.N and lower Tb.Sp compared with DMFx_VD (p = 0.006, p = 0.012, respectively) and CTL (p = 0.026, p = 0.035, respectively). DMFx group and healthy controls showed similar BV/TV, Tb.Th, Tb.N, Tb.Sp, Conn.D, DA, and FD (p = 0.771, p = 0.503, p = 0.285, p = 0.266, p = 0.208, p = 0.235, p = 0.688, respectively), while SMI was significantly higher in controls (p = 0.005). Two distinct phenotypes of bone fragility were identified in T2DM patients: patients with vascular complications showed impaired trabecular microarchitecture, whereas bone fragility in the group without vascular complications was independent on trabecular microarchitecture pattern. Such heterogeneity among T2DM patients may explain contradicting literature data and may set a basis for further studies to evaluate fracture risk related to T2DM.
| S-EPMC8302969 | biostudies-literature
Project description:Achondroplasia (ACH), the most common form of human dwarfism is caused by a mutation in the Fibroblast Growth Factor Receptor 3 (FGFR3) gene, resulting in constitutive activation of the receptor. In order to gain insight into molecular mechanisms involved in the physiopathology, a conditional mouse model carrying the Y367C mutation corresponding to the human Y373C TDI mutation was produced (fgfr3neoY367C/+). Crossing these mice with CMV-CRE mice produces dwarf fgfr3Y367C/+ and fgfr3+/+ controls littermates. Dwarf fgfr3Y367C/+ mice exhibited skeletal dysplasia at birth, the phenotype becoming progressively more pronounced as the mice got older, with reduced length of long bone, narrow trunk, short ribs and macrocephaly. Histological examination of epiphyseal growth plates showed a disorganized growth plate, with reduced size of the hypertrophic and proliferative zone and an accelerated secondary ossification center formation (full phenotype description in Pannier S et al, Activating Fgfr3 Y367C mutation causes hearing loss and inner ear defect in a mouse model of chondrodysplasia. Biochimica et biophysica acta 2009; Pannier S et al, Delayed bone age due to a dual effect of FGFR3 mutation in Achondroplasia. Bone 2010; Jonquoy A et al, A novel tyrosine kinase inhibitor restores chondrocyte differentiation and promotes bone growth in a gain-of-function Fgfr3 mouse model. Human molecular genetics 2012; Martin L et al, Constitutively-active FGFR3 disrupts primary cilium length and IFT20 trafficking in various chondrocyte models of achondroplasia. Human molecular genetics 2018).
2020-12-31 | GSE145821 | GEO
Project description:In a phase 2 trial of 222 postmenopausal women with osteoporosis aged 55 to 85 years randomized to one of three different doses of abaloparatide-SC, subcutaneous teriparatide, or placebo for 24 weeks, abaloparatide-SC resulted in improvements in skeletal microarchitecture as measured by the trabecular bone score. INTRODUCTION:Subcutaneous abaloparatide (abaloparatide-SC) increases total hip and lumbar spine bone mineral density and reduces vertebral and non-vertebral fractures. In this study, we analyzed the extent to which abaloparatide-SC improves skeletal microarchitecture, assessed indirectly by trabecular bone score (TBS). METHODS:This is a post hoc analysis of a phase 2 trial of 222 postmenopausal women with osteoporosis aged 55 to 85 years randomized to abaloparatide-SC (20, 40, or 80 ?g), subcutaneous teriparatide (20 ?g), or placebo for 24 weeks. TBS was measured from lumbar spine dual X-ray absorptiometry (DXA) images in 138 women for whom the DXA device was TBS software compatible. Assessments were made at baseline, 12 and 24 weeks. Between-group differences were assessed by generalized estimating equations adjusted for relevant baseline characteristics, and a pre-determined least significant change analysis was performed. RESULTS:After 24 weeks, TBS increased significantly by 2.27, 3.14, and 4.21% versus baseline in participants on 20, 40, and 80 ?g abaloparatide-SC daily, respectively, and by 2.21% in those on teriparatide (p?<?0.05 for each). The TBS in the placebo group declined by 1.08%. The TBS increase in each treatment group was significantly higher than placebo at 24 weeks (p?<?0.0001 for each) after adjustment for age, BMI, and baseline TBS. A dose-response was observed at 24 weeks across the three doses of abaloparatide-SC and placebo (p?=?0.02). The increase in TBS in the abaloparatide-SC 80 ?g group was significantly greater than TPTD (p?<?0.03). CONCLUSIONS:These results are consistent with an effect of abaloparatide-SC to improve lumbar spine skeletal microarchitecture, as assessed by TBS.
| S-EPMC5818587 | biostudies-literature