Mechanical properties of femoral trabecular bone in dogs

BACKGROUND: Studying mechanical properties of canine trabecular bone is important for a better understanding of fracture mechanics or bone disorders and is also needed for numerical simulation of canine femora. No detailed data about elastic moduli and degrees of anisotropy of canine femoral trabecular bone has been published so far, hence the purpose of this study was to measure the elastic modulus of trabecular bone in canine femoral heads by ultrasound testing and to assess whether assuming isotropy of the cancellous bone in femoral heads in dogs is a valid simplification. METHODS: From 8 euthanized dogs, both femora were obtained and cubic specimens were cut from the centre of the femoral head which were oriented along the main pressure and tension trajectories. The specimens were tested using a 100 MHz ultrasound transducer in all three orthogonal directions. The directional elastic moduli of trabecular bone tissue and degrees of anisotropy were calculated. RESULTS: The elastic modulus along principal bone trajectories was found to be 11.2 GPa ± 0.4, 10.5 ± 2.1 GPa and 10.5 ± 1.8 GPa, respectively. The mean density of the specimens was 1.40 ± 0.09 g/cm(3). The degrees of anisotropy revealed a significant inverse relationship with specimen densities. No significant differences were found between the elastic moduli in x, y and z directions, suggesting an effective isotropy of trabecular bone tissue in canine femoral heads. DISCUSSION: This study presents detailed data about elastic moduli of trabecular bone tissue obtained from canine femoral heads. Limitations of the study are the relatively small number of animals investigated and the measurement of whole specimen densities instead of trabecular bone densities which might lead to an underestimation of Young's moduli. Publications on elastic moduli of trabecular bone tissue present results that are similar to our data. CONCLUSION: This study provides data about directional elastic moduli and degrees of anisotropy of canine femoral head trabecular bone and might be useful for biomechanical modeling of proximal canine femora

Effect of trabecular bone loss on cortical strain rate during impact in an in vitro model of avian femur

BACKGROUND: Osteoporotic hip fractures occur due to loss of cortical and trabecular bone mass and consequent degradation in whole bone strength. The direct cause of most fractures is a fall, and hence, characterizing the mechanical behavior of a whole osteopenic bone under impact is important. However, very little is known about the mechanical interactions between cortical and trabecular bone during impact, and it is specifically unclear to what extent epiphyseal trabecular bone contributes to impact resistance of whole bones. We hypothesized that trabecular bone serves as a structural support to the cortex during impact, and hence, loss of a critical mass of trabecular bone reduces internal constraining of the cortex, and, thereby, decreases the impact tolerance of the whole bone. METHODS: To test this hypothesis, we conducted cortical strain rate measurements in adult chicken's proximal femora subjected to a Charpy impact test, after removing different trabecular bone core masses to simulate different osteopenic severities. RESULTS: We found that removal of core trabecular bone decreased by ~10-fold the cortical strain rate at the side opposite to impact (p < 0.01), i.e. from 359,815 ± 1799 μm/m per second (mean ± standard error) for an intact (control) specimen down to 35,997 ± 180 μm/m per second where 67% of the total trabecular bone mass (~0.7 grams in adult chicken) were removed. After normalizing the strain rate by the initial weight of bone specimens, a sigmoid relation emerged between normalized strain rate and removed mass of trabecular bone, showing very little effect on the cortex strain rate if below 10% of the trabecular mass is removed, but most of the effect was already apparent for less than 30% trabecular bone loss. An analytical model of the experiments supported this behavior. CONCLUSION: We conclude that in our in vitro avian model, loss of over 10% of core trabecular bone substantially altered the deformation response of whole bone to impact, which supports the above hypothesis and indicates that integrity of trabecular bone is critical for resisting impact loads

Cells of the human intestinal tract mapped across space and time

The cellular landscape of the human intestinal tract is dynamic throughout life, developing in utero and changing in response to functional requirements and environmental exposures. Here, to comprehensively map cell lineages, we use single-cell RNA sequencing and antigen receptor analysis of almost half a million cells from up to 5 anatomical regions in the developing and up to 11 distinct anatomical regions in the healthy paediatric and adult human gut. This reveals the existence of transcriptionally distinct BEST4 epithelial cells throughout the human intestinal tract. Furthermore, we implicate IgG sensing as a function of intestinal tuft cells. We describe neural cell populations in the developing enteric nervous system, and predict cell-type-specific expression of genes associated with Hirschsprung’s disease. Finally, using a systems approach, we identify key cell players that drive the formation of secondary lymphoid tissue in early human development. We show that these programs are adopted in inflammatory bowel disease to recruit and retain immune cells at the site of inflammation. This catalogue of intestinal cells will provide new insights into cellular programs in development, homeostasis and disease

Exome-Wide Association Study of Competitive Performance in Elite Athletes

The aim of the study was to identify genetic variants associated with personal best scores in Turkish track and field athletes and to compare allelic frequencies between sprint/power and endurance athletes and controls using a whole-exome sequencing (WES) approach, followed by replication studies in independent cohorts. The discovery phase involved 60 elite Turkish athletes (31 sprint/power and 29 endurance) and 20 ethnically matched controls. The replication phase involved 1132 individuals (115 elite Russian sprinters, 373 elite Russian endurance athletes (of which 75 athletes were with VO2max measurements), 209 controls, 148 Russian and 287 Finnish individuals with muscle fiber composition and cross-sectional area (CSA) data). None of the single nucleotide polymorphisms (SNPs) reached an exome-wide significance level (p < 2.3 × 10−7) in genotype–phenotype and case–control studies of Turkish athletes. However, of the 53 nominally (p < 0.05) associated SNPs, four functional variants were replicated. The SIRT1 rs41299232 G allele was significantly over-represented in Turkish (p = 0.047) and Russian (p = 0.018) endurance athletes compared to sprint/power athletes and was associated with increased VO2max (p = 0.037) and a greater proportion of slow-twitch muscle fibers (p = 0.035). The NUP210 rs2280084 A allele was significantly over-represented in Turkish (p = 0.044) and Russian (p = 0.012) endurance athletes compared to sprint/power athletes. The TRPM2 rs1785440 G allele was significantly over-represented in Turkish endurance athletes compared to sprint/power athletes (p = 0.034) and was associated with increased VO2max (p = 0.008). The AGRN rs4074992 C allele was significantly over-represented in Turkish sprint/power athletes compared to endurance athletes (p = 0.037) and was associated with a greater CSA of fast-twitch muscle fibers (p = 0.024). In conclusion, we present the first WES study of athletes showing that this approach can be used to identify novel genetic markers associated with exercise- and sport-related phenotypes

Effect of repeated in vivo microCT imaging on the properties of the mouse tibia

In longitudinal studies, in vivo micro-Computed Tomography (microCT) imaging is used to investigate bone changes over time due to interventions in mice. However, ionising radiation can provoke significant variations in bone morphometric parameters. In a previous study, we evaluated the effect of reducing the integration time on the properties of the mouse tibia measured from microCT images. A scanning procedure (100 ms integration time, 256 mGy nominal radiation dose) was selected as the best compromise between image quality and radiation dose induced on the animal. In this work, the effect of repeated in vivo scans has been evaluated using the selected procedure. The right tibia of twelve female C57BL/6 (six wild type, WT, six ovariectomised, OVX) and twelve BALB/c (six WT, six OVX) mice was scanned every two weeks, starting at week 14 of age. At week 24, mice were sacrificed and both tibiae were scanned. Standard trabecular and cortical morphometric parameters were calculated. The spatial distribution of densitometric parameters (e.g. bone mineral content) was obtained by dividing each tibia in 40 partitions. Stiffness and strength in compression were estimated using homogeneous linear elastic microCT-based micro-Finite Element models. Differences between right (irradiated) and left (non-irradiated control) tibiae were evaluated for each parameter. The irradiated tibiae had higher Tb.Th (+3.3%) and Tb.Sp (+11.6%), and lower Tb.N (-14.2%) compared to non-irradiated tibiae, consistently across both strains and intervention groups. A reduction in Tb.BV/TV (-14.9%) was also observed in the C57BL/6 strain. In the OVX group, a small reduction was also observed in Tt.Ar (-5.0%). In conclusion, repeated microCT scans (at 256 mGy, 5 scans, every two weeks) had limited effects on the mouse tibia, compared to the expected changes induced by bone treatments. Therefore, the selected scanning protocol is acceptable for measuring the effect of bone interventions in vivo

Patient-specific finite element estimated femur strength as a predictor of the risk of hip fracture: the effect of methodological determinants

Summary: A finite element modelling pipeline was adopted to predict femur strength in a retrospective cohort of 100 women. The effects of the imaging protocol and the meshing technique on the ability of the femur strength to classify the fracture and the control groups were analysed. Introduction: The clinical standard to estimate the risk of osteoporotic hip fracture is based on the areal bone mineral density (aBMD). A few retrospective studies have concluded that finite element (FE)-based femoral strength is a better classifier of fracture and control groups than the aBMD, while others could not find significant differences. We investigated the effect of the imaging protocol and of the FE modelling techniques on the discriminatory power of femoral strength. Methods: A retrospective cohort of 100 post-menopausal women (50 with hip fracture, 50 controls) was examined. Each subject received a dual-energy absorptiometry (DXA) exam and a computed tomography (CT) scan of the proximal femur region. Each case was modelled a number of times, using different modelling pipelines, and the results were compared in terms of accuracy in discriminating the fracture and the control cases. The baseline pipeline involved local anatomical orientation and mesh morphing. Revised pipelines involved global anatomical orientation using a full-femur atlas registration and an optimised meshing algorithm. Minimum physiological (MPhyS) and pathological (MPatS) strengths were estimated for each subject. Area under the receiver operating characteristic (ROC) curve (AUC) was calculated to compare the ability of MPhyS, MPatS and aBMD to classify the control and the cases. Results: Differences in the modelling protocol were found to considerably affect the accuracy of the FE predictors. For the most optimised protocol, logistic regression showed aBMD Neck , MPhyS and MPatS to be significantly associated with the facture status, with AUC of 0.75, 0.75 and 0.79, respectively. Conclusion: The study emphasized the necessity of modelling the whole femur anatomy to develop a robust FE-based tool for hip fracture risk assessment. FE-strength performed only slightly better than the aBMD in discriminating the fracture and control cases. Differences between the published studies can be explained in terms of differences in the modelling protocol and cohort design

Characterisation of time-dependent mechanical behaviour of trabecular bone and its constituents

Trabecular bone is a porous composite material which consists of a mineral phase (mainly hydroxyapatite), organic phase (mostly type I collagen) and water assembled into a complex, hierarchical structure. In biomechanical modelling, its mechanical response to loads is generally assumed to be instantaneous, i.e. it is treated as a time-independent material. It is, however, recognised that the response of trabecular bone to loads is time-dependent. Study of this time-dependent behaviour is important in several contexts such as: to understand energy dissipation ability of bone; to understand the age-related non-traumatic fractures; to predict implant loosening due to cyclic loading; to understand progressive vertebral deformity; and for pre-clinical evaluation of total joint replacement. To investigate time-dependent behaviour, bovine trabecular bone samples were subjected to compressive loading, creep, unloading and recovery at multiple load levels (corresponding to apparent strain of 2,000-25,000 με). The results show that: the time-dependent behaviour of trabecular bone comprises of both recoverable and irrecoverable strains; the strain response is nonlinearly related to applied load levels; and the response is associated with bone volume fraction. It was found that bone with low porosity demonstrates elastic stiffening followed by elastic softening, while elastic softening is demonstrated by porous bone at relatively low loads. Linear, nonlinear viscoelastic and nonlinear viscoelastic-viscoplastic constitutive models were developed to predict trabecular bone’s time-dependent behaviour. Nonlinear viscoelastic constitutive model was found to predict the recovery behaviour well, while nonlinear viscoelastic-viscoplastic model predicts the full creep-recovery behaviour reasonably well. Depending on the requirements all these models can be used to incorporate time-dependent behaviour in finite element models. To evaluate the contribution of the key constituents of trabecular bone and its microstructure, tests were conducted on demineralised and deproteinised samples. Reversed cyclic loading experiments (tension to compression) were conducted on demineralised trabecular bone samples. It was found that demineralised bone exhibits asymmetric mechanical response - elastic stiffening in tension and softening in compression. This tension to compression transition was found to be smooth. Tensile multiple-load-creep-unload-recovery experiments on demineralised trabecular samples show irrecoverable strain (or residual strain) even at the low stress levels. Demineralised trabecular bone samples demonstrate elastic stiffening with increasing load levels in tension, and their time-dependent behaviour is nonlinear with respect to applied loads . Nonlinear viscoelastic constitutive model was developed which can predict its recovery behaviour well. Experiments on deproteinised samples showed that their modulus and strength are reasonably well related to bone volume fraction. The study considers an application of time-dependent behaviour of trabecular bone. Time-dependent properties are assigned to trabecular bone in a bone-screw system, in which the screw is subjected to cyclic loading. It is found that separation between bone and the screw at the interface can increase with increasing number of cycles which can accentuate loosening. The relative larger deformation occurs when this system to be loaded at the higher loading frequency. The deformation at the bone-screw interface is related to trabecular bone’s bone volume fraction; screws in a more porous bone are at a higher risk of loosening

A multiscale model to predict current absolute risk of femoral fracture in a postmenopausal population

Osteoporotic hip fractures are a major healthcare problem. Fall severity and bone strength are important risk factors of hip fracture. This study aims to obtain a mechanistic explanation for fracture risk in dependence of these risk factors. A novel modelling approach is developed that combines models at different scales to overcome the challenge of a large space–time domain of interest and considers the variability of impact forces between potential falls in a subject. The multiscale model and its component models are verified with respect to numerical approximations made therein, the propagation of measurement uncertainties of model inputs is quantified, and model predictions are validated against experimental and clinical data. The main results are model predicted absolute risk of current fracture (ARF0) that ranged from 1.93 to 81.6% (median 36.1%) for subjects in a retrospective cohort of 98 postmenopausal British women (49 fracture cases and 49 controls); ARF0 was computed up to a precision of 1.92 percentage points (pp) due to numerical approximations made in the model; ARF0 possessed an uncertainty of 4.00 pp due to uncertainties in measuring model inputs; ARF0 classified observed fracture status in the above cohort with AUC = 0.852 (95% CI 0.753–0.918), 77.6% specificity (95% CI 63.4–86.5%) and 81.6% sensitivity (95% CI 68.3–91.1%). These results demonstrate that ARF0 can be computed using the model with sufficient precision to distinguish between subjects and that the novel mechanism of fracture risk determination based on fall dynamics, hip impact and bone strength can be considered validated