High-resolution Quantitative Computed Tomography Research Articles

Femur strength predictions by nonlinear homogenized voxel finite element models reflect the microarchitecture of the femoral neck

In the human femoral neck, the contribution of the cortical and trabecular architecture to mechanical strength is known to depend on the load direction.In this work, we investigate if QCT-derived homogenized voxel finite element (hvFE) simulations of varying hip loading conditions can be used to study the architecture of the femoral neck. The strength of 19 pairs of human femora was measured ex vivo using nonlinear hvFE models derived from high-resolution peripheral QCT scans (voxel size: 30.3 µm). Standing and side-backwards falling loads were modeled. Quasi-static mechanical tests were performed on 20 bones for comparison. Associations of femur strength with volumetric bone mineral density (vBMD) or microstructural parameters of the femoral neck obtained from high-resolution QCT were compared between mechanical tests and simulations and between standing and falling loads.Proximal femur strength predictions by hvFE models were positively associated with the vBMD of the femoral neck (R² > 0.61, p < 0.001), as well as with its cortical thickness (R² > 0.27, p < 0.001), trabecular bone volume fraction (R² = 0.42, p < 0.001) and with the first two principal components of the femoral neck architecture (R² > 0.38, p < 0.001). Associations between femur strength and femoral neck microarchitecture were stronger for one-legged standing than for side-backwards falling. For both loading directions, associations between structural parameters and femur strength from hvFE models were in good agreement with those from mechanical tests. This suggests that hvFE models can reflect the load-direction-specific contribution of the femoral neck microarchitecture to femur strength.

Improved accuracy in the assessment of vertebral cortical thickness by quantitative computed tomography using the Iterative Convolution OptimizatioN (ICON) method.

Vertebral whole bone strength is substantially affected by cortical bone properties. Disease and therapy may affect cancellous and cortical bone differently. Unlike Dual X-ray Absorptiometry (DXA), Quantitative Computed Tomography (QCT) permits selective assessment of cortical and cancellous bone, but image quality limits the accuracy. We present an image processing method specifically adopted to thin cortices that substantially improves accuracy. Ten human vertebrae embedded in epoxy resin were imaged using clinical QCT and High-Resolution QCT (HR-QCT) protocols, both acquired on a clinical whole body CT scanner, whereas high resolution peripheral QCT (HR-pQCT) was used as gold standard. Microstructural variables and BMD were calculated using in-house software StructuralInsight for QCT and HR-QCT and the manufacturer's μCT evaluation software for HR-pQCT. An adjusted measure, a deconvolved cortical thickness (dcCt.Th), corrected for partial volume effects, was derived applying the new Iterative Convolution OptimizatioN (ICON) method. Direct measurements of cortical thickness (Ct.Th) showed substantial overestimation with mean ± standard deviation of 1.8 ± 0.5 mm for QCT and 1.5 ± 0.3 mm for HR-QCT compared to 0.37 ± 0.07 mm using HR-pQCT. Correlations of both QCT (r2 = 0.05, p > 0.5.) and HR-QCT (r2 = 0.38, p = 0.060) with the gold standard HR-pQCT were not significant. Also QCT-based BMD and BMC as well as HR-QCT-based BMD did not show a significant correlation with the gold standard approach. Only HR-QCT-based BMC showed a modest correlation (r2 = 0.59, p = 0.01) After applying ICON corrections, dcCt.Th resulted in 0.52 ± 0.09 mm for QCT and 0.43 ± 0.07 mm for HR-QCT, both significantly correlated to HR-pQCT (r2 = 0.75, p = 0.0012 and r2 = 0.93, p < 0.0001, respectively). The average overestimation bias of Ct.Th was reduced from (402 ± 157)% to (45 ± 17)% for QCT and from (330 ± 69)% to (19 ± 8)% for HR-QCT. Due to inaccurate segmentation uncorrected QCT-based Ct.Th measures as well as BMD and BMC showed no correlation to HR-pQCT and thus such bias cortical data can be misleading. The application of ICON reduced random overestimation bias to about 50 μm and 20 μm for QCT and HR-QCT, respectively, leading to a recovery of a significant correlation with the reference data of HR-pQCT. This reveals the potential for fairly accurate assessment of cortical thickness, allowing to better characterize cortical mechanical competence. These results warrant testing of the performance in vivo.

Influence of Teriparatide and Ibandronate on Cortical Bone in New Zealand White Rabbits: A HR-QCT Study.

Teriparatide (TPTD) is known to increase the cortical thickness and porosity. The purpose of the present study was to determine whether switching from TPTD to ibandronate (IBN) would be useful for improving cortical bone parameters as assessed using high-resolution quantitative computed tomography (HR-QCT) analyses in mature rabbits. Forty-two female New Zealand white rabbits (18-22weeks old) were randomized into six groups of 7 animals each as follows: 4-week vehicle administration group, 4-week TPTD administration group (20μg/kg, subcutaneously [s.c.], daily), 12-week vehicle administration group, 4-week TPTD administration+8-week vehicle administration group, 4-week TPTD administration+8-week lower-dose IBN administration group (20 μg/kg, s.c., every 4weeks), and 4-week TPTD administration+8-week higher-dose IBN administration group (100μg/kg, s.c., every 4weeks). After the 4- or 12-week experimental period, the cortical bone of the distal femoral diaphysis was processed for HR-QCT analysis. The 4-week TPTD administration increased the pore ratio, number, and density as well as the cortical area, thickness, and bone mineral content (BMC), without significant influencing the volumetric bone mineral density (BMD). The 4-week TPTD administration+8-week vehicle administration decreased the pore ratio, number, and density as well as the cortical area and thickness, compared with the 4-week TPTD administration, but the pore ratio, cortical area, and thickness were still higher compared with the 12-week vehicle administration. The 4-week TPTD administration+8-week higher-dose IBN administration, but not the 4-week TPTD administration+8-week lower-dose IBN administration, increased the cortical area, thickness, BMC, and volumetric BMD and decreased the pore ratio, but not the pore number or density, compared with the 4-week TPTD administration+8-week vehicle administration. These results suggest that higher-dose IBN after TPTD therapy has a beneficial effect on the BMC, volumetric BMD, cortical area, thickness, and porosity in mature rabbits.

Bone‐marrow densitometry: Assessment of marrow space of human vertebrae by single energy high resolution‐quantitative computed tomography

Accurate noninvasive assessment of vertebral bone marrow fat fraction is important for diagnostic assessment of a variety of disorders and therapies known to affect marrow composition. Moreover, it provides a means to correct fat-induced bias of single energy quantitative computed tomography (QCT) based bone mineral density (BMD) measurements. The authors developed new segmentation and calibration methods to obtain quantitative surrogate measures of marrow-fat density in the axial skeleton. The authors developed and tested two high resolution-QCT (HR-QCT) based methods which permit segmentation of bone voids in between trabeculae hypothesizing that they are representative of bone marrow space. The methods permit calculation of marrow content in units of mineral equivalent marrow density (MeMD). The first method is based on global thresholding and peeling (GTP) to define a volume of interest away from the transition between trabecular bone and marrow. The second method, morphological filtering (MF), uses spherical elements of different radii (0.1-1.2 mm) and automatically places them in between trabeculae to identify regions with large trabecular interspace, the bone-void space. To determine their performance, data were compared ex vivo to high-resolution peripheral CT (HR-pQCT) images as the gold-standard. The performance of the methods was tested on a set of excised human vertebrae with intact bone marrow tissue representative of an elderly population with low BMD. 86% (GTP) and 87% (MF) of the voxels identified as true marrow space on HR-pQCT images were correctly identified on HR-QCT images and thus these volumes of interest can be considered to be representative of true marrow space. Within this volume, MeMD was estimated with residual errors of 4.8 mg/cm(3) corresponding to accuracy errors in fat fraction on the order of 5% both for GTP and MF methods. The GTP and MF methods on HR-QCT images permit noninvasive localization and densitometric assessment of marrow fat with residual accuracy errors sufficient to study disorders and therapies known to affect bone marrow composition. Additionally, the methods can be used to correct BMD for fat induced bias. Application and testing in vivo and in longitudinal studies are warranted to determine the clinical performance and value of these methods.

Administration of romosozumab improves vertebral trabecular and cortical bone as assessed with quantitative computed tomography and finite element analysis

Romosozumab inhibits sclerostin, thereby increasing bone formation and decreasing bone resorption. This dual effect of romosozumab leads to rapid and substantial increases in areal bone mineral density (aBMD) as measured by dual-energy X-ray absorptiometry (DXA). In a phase 1b, randomized, double-blind, placebo-controlled study, romosozumab or placebo was administered to 32 women and 16 men with low aBMD for 3months, with a further 3-month follow-up: women received six doses of 1 or 2mg/kg every 2weeks (Q2W) or three doses of 2 or 3mg/kg every 4weeks (Q4W); men received 1mg/kg Q2W or 3mg/kg Q4W. Quantitative computed tomography (QCT) scans at lumbar (L1–2) vertebrae and high-resolution QCT (HR-QCT) scans at thoracic vertebra (T12) were analyzed in a subset of subjects at baseline, month 3, and month 6. The QCT subset included 24 romosozumab and 9 placebo subjects and the HR-QCT subset included 11 romosozumab and 3 placebo subjects. The analyses pooled the romosozumab doses. Linear finite element modeling of bone stiffness was performed. Compared with placebo, the romosozumab group showed improvements at month 3 for trabecular BMD by QCT and HR-QCT, HR-QCT trabecular bone volume fraction (BV/TV) and separation, density-weighted cortical thickness, and QCT stiffness (all p<0.05). At month 6, improvements from baseline were observed in QCT trabecular BMD and stiffness, and in HR-QCT BMD, trabecular BV/TV and separation, density-weighted cortical thickness, and stiffness in the romosozumab group (all p<0.05 compared with placebo). The mean (SE) increase in HR-QCT stiffness with romosozumab from baseline was 26.9%±6.8% and 35.0%±6.8% at months 3 and 6, respectively; subjects administered placebo had changes of −2.7%±13.4% and −6.4%±13.4%, respectively. In conclusion, romosozumab administered for 3months resulted in rapid and large improvements in trabecular and cortical bone mass and structure as well as whole bone stiffness, which continued 3months after the last romosozumab dose.

Quantitative computed tomography-based finite element analysis predictions of femoral strength and stiffness depend on computed tomography settings

The aim of the present study was to compare proximal femur strength and stiffness obtained experimentally with estimations from Finite Element Analysis (FEA) models derived from Quantitative Computed Tomography (QCT) scans acquired at two different scanner settings. QCT/FEA models could potentially aid in diagnosis and treatment of osteoporosis but several drawbacks still limit their predictive ability. One potential reason is that the models are still sensitive to scanner settings which could lead to changes in assigned material properties, thus limiting their results accuracy and clinical effectiveness. To find the mechanical properties we fracture tested 44 proximal femora in a sideways fall-on-the-hip configuration. Before testing, we CT scanned all femora twice, first at high resolution scanner settings, and second at low resolution scanner settings and built 88 QCT/FEA models of femoral strength and stiffness. The femoral set neck bone mineral density, as measured by DXA, uniformly covered the range from osteoporotic to normal. This study showed that the femoral strength and stiffness values predicted from high and low resolution scans were significantly different (p<0.0001). Strength estimated from high resolution QCT scans was larger for osteoporotic, but smaller for normal and osteopenic femora when compared to low resolution scans. In addition, stiffness estimated from high resolution scans was consistently larger than stiffness obtained from low resolution scans over the entire femoral dataset. While QCT/FEA techniques hold promise for use in clinical settings we provided evidence that further improvements are required to increase robustness in their predictive power under different scanner settings and modeling assumptions.

Imaging assessment of a portable hemodialysis device: detection of possible failure modes and monitoring of functional performance.

BackgroundThe purpose of this study was to investigate the utility and limitations of various imaging modalities in the noninvasive assessment of a novel compact hemodialyzer under development for renal replacement therapy, with specific aim towards monitoring its functional performance.MethodsThe prototype is a 4×3×6 cm aluminum cartridge housing “blood” and “dialysate” flow paths arranged in parallel. A sheet of semipermeable silicon nanopore membranes forms the blood-dialysate interface, allowing passage of small molecules. Blood flow was simulated using a peristaltic pump to instill iodinated contrast through the blood compartment, while de-ionized water was instilled through the dialysate compartment at a matched rate in the countercurrent direction. Images were acquired under these flow conditions using multi-detector computed tomography (MDCT), fluoroscopy, high-resolution quantitative computed tomography (HR-QCT), and magnetic resonance imaging (MRI). MDCT was used to monitor contrast diffusion efficiency by plotting contrast density as a function of position along the path of flow through the cartridge during steady state infusion at 1 and 20 mL/min. Both linear and exponential regressions were used to model contrast decay along the flow path.ResultsBoth linear and exponential models of contrast decay appeared to be reasonable approximations, yielding similar results for contrast diffusion during a single pass through the cartridge. There was no measurable difference in contrast diffusion when comparing 1 mL/min and 20 mL/min flow rates. Fluoroscopy allowed a gross qualitative assessment of flow within the device, and revealed flow inhomogeneity within the corner of the cartridge opposite the blood inlet port. MRI and HR-QCT were both severely limited due to the paramagnetic properties and high atomic number of the target material, respectively. During testing, we encountered several causes of device malfunction, including leak formation, trapped gas, and contrast-mediated nanopore clogging. We illustrate the imaging manifestations of each.ConclusionsDespite the inherent challenges in imaging a predominantly metallic device, some modalities show potential in the non-invasive assessment of a novel compact hemodialyzer. The approaches described here could potentially be translated to device evaluation in the implanted setting.

Comparative effects of teriparatide and risedronate in glucocorticoid-induced osteoporosis in men: 18-month results of the EuroGIOPs trial

Data on treatment of glucocorticoid-induced osteoporosis (GIO) in men are scarce. We performed a randomized, open-label trial in men who have taken glucocorticoids (GC) for ≥3 months, and had an areal bone mineral density (aBMD) T-score ≤ –1.5 standard deviations. Subjects received 20 μg/d teriparatide (n = 45) or 35 mg/week risedronate (n = 47) for 18 months. Primary objective was to compare lumbar spine (L1–L3) BMD measured by quantitative computed tomography (QCT). Secondary outcomes included BMD and microstructure measured by high-resolution QCT (HRQCT) at the 12th thoracic vertebra, biomechanical effects for axial compression, anterior bending, and axial torsion evaluated by finite element (FE) analysis from HRQCT data, aBMD by dual X-ray absorptiometry, biochemical markers, and safety. Computed tomography scans were performed at 0, 6, and 18 months. A mixed model repeated measures analysis was performed to compare changes from baseline between groups. Mean age was 56.3 years. Median GC dose and duration were 8.8 mg/d and 6.4 years, respectively; 39.1% of subjects had a prevalent fracture, and 32.6% received prior bisphosphonate treatment. At 18 months, trabecular BMD had significantly increased for both treatments, with significantly greater increases with teriparatide (16.3% versus 3.8%; p = 0.004). HRQCT trabecular and cortical variables significantly increased for both treatments with significantly larger improvements for teriparatide for integral and trabecular BMD and bone surface to volume ratio (BS/BV) as a microstructural measure. Vertebral strength increases at 18 months were significant in both groups (teriparatide: 26.0% to 34.0%; risedronate: 4.2% to 6.7%), with significantly higher increases in the teriparatide group for all loading modes (0.005 < p < 0.015). Adverse events were similar between groups. None of the patients on teriparatide but five (10.6%) on risedronate developed new clinical fractures (p = 0.056). In conclusion, in this 18-month trial in men with GIO, teriparatide showed larger improvements in spinal BMD, microstructure, and FE-derived strength than risedronate.

New horizons for the in vivo assessment of major aspects of bone quality

SummaryThe Biomechanically founded individualised osteoporosis Assessment and treatment (BioAsset) consortium pursues experimental and clinical studies in the context of skeletal effects of bisphosphonate treatment. Here, first results using newly developed diagnostic methods in a set of vertebral bone specimen obtained from donors with documented bisphosphonate history ranging from 0 to more than 5 years of treatment are presented. A new thoracolumbar quantitative computed tomography (QCT) protocol covering T6 to L4 plus high-resolution QCT (HRQCT) assessment of T12 were compared with high-resolution peripheral QCT (HRpQCT) and micro-CT scans of excised specimens serving as gold standard techniques. Finite element (FE) modelling was performed. Material, ultrastructural, and micromechanical properties were tested on a set of single trabeculae obtained from the donor specimens. A newly developed quantitative ultrasound (QUS) device for measuring the anisotropy of cortical material properties at the tibia was designed and built. The thoracolumbar QCT protocol permitted in situ imaging with good image quality and automated segmentation of vertebral bodies in the whole range from T6 to L4. The duration of bisphosphonate treatment was significantly associated with increased levels of mineralization and this effect could be measured with HRQCT performed on excised specimens. Microstructural parameters contributed to vertebral bone strength modelled by FE analysis independently of bone mineral density. The new QUS tibia scanner permitted measuring the acoustical anisotropy of reference materials. Taken together, these results document that new methods developed in BioAsset permit a more comprehensive assessment of bone fragility. The set of donor specimens with a documented history of bisphosphonate treatment allows for the assessment of the effects of long-term treatment from the organ down to the tissue and material level. These results will ultimately be linked to the parallel clinical study to provide guidance for determining the optimum duration of bisphosphonate treatment to reduce the incidence of osteoporotic fractures.

High resolution quantitative computed tomography-based assessment of trabecular microstructure and strength estimates by finite-element analysis of the spine, but not DXA, reflects vertebral fracture status in men with glucocorticoid-induced osteoporosis

High-resolution quantitative computed tomography (HRQCT)-based analysis of spinal bone density and microstructure, finite element analysis (FEA), and DXA were used to investigate the vertebral bone status of men with glucocorticoid-induced osteoporosis (GIO). DXA of L1–L3 and total hip, QCT of L1–L3, and HRQCT of T12 were available for 73 men (54.6±14.0years) with GIO. Prevalent vertebral fracture status was evaluated on radiographs using a semi-quantitative (SQ) score (normal=0 to severe fracture=3), and the spinal deformity index (SDI) score (sum of SQ scores of T4 to L4 vertebrae). Thirty-one (42.4%) subjects had prevalent vertebral fractures. Cortical BMD (Ct.BMD) and thickness (Ct.Th), trabecular BMD (Tb.BMD), apparent trabecular bone volume fraction (app.BV/TV), and apparent trabecular separation (app.Tb.Sp) were analyzed by HRQCT. Stiffness and strength of T12 were computed by HRQCT-based nonlinear FEA for axial compression, anterior bending and axial torsion. In logistic regressions adjusted for age, glucocorticoid dose and osteoporosis treatment, Tb.BMD was most closely associated with vertebral fracture status (standardized odds ratio [sOR]: Tb.BMD T12: 4.05 [95% CI: 1.8–9.0], Tb.BMD L1–L3: 3.95 [1.8–8.9]). Strength divided by cross-sectional area for axial compression showed the most significant association with spine fracture status among FEA variables (2.56 [1.29–5.07]). SDI was best predicted by a microstructural model using Ct.Th and app.Tb.Sp (r2=0.57, p<0.001). Spinal or hip DXA measurements did not show significant associations with fracture status or severity.In this cross-sectional study of males with GIO, QCT, HRQCT-based measurements and FEA variables were superior to DXA in discriminating between patients of differing prevalent vertebral fracture status. A microstructural model combining aspects of cortical and trabecular bone reflected fracture severity most accurately.

Bone texture analysis of human femurs using a new device (BMA™) improves failure load prediction

We measured bone texture parameters of excised human femurs with a new device (BMA™). We also measured bone mineral density by DXA and investigated the performance of these parameters in the prediction of failure load. Our results suggest that bone texture parameters improve failure load prediction when added to bone mineral density. Bone mineral density (BMD) is a strong determinant of bone strength. However, nearly half of the fractures occur in patients with BMD which does not reach the osteoporotic threshold. In order to assess fracture risk properly, other factors are important to be taken into account such as clinical risk factors as well as macro- and microarchitecture of bone. Bone microarchitecture is usually assessed by high-resolution QCT, but this cannot be applied in routine clinical settings due to irradiation, cost and availability concerns. Texture analysis of bone has shown to be correlated to bone strength. We used a new device to get digitized X-rays of 12 excised human femurs in order to measure bone texture parameters in three different regions of interest (ROIs). We investigated the performance of these parameters in the prediction of the failure load using biomechanical tests. Texture parameters measured were the fractal dimension (Hmean), the co-occurrence matrix, and the run length matrix. We also measured bone mineral density by DXA in the same ROIs as well as in standard DXA hip regions. The Spearman correlation coefficient between BMD and texture parameters measured in the same ROIs ranged from -0.05 (nonsignificant (NS)) to 0.57 (p = 0.003). There was no correlation between Hmean and co-occurrence matrix nor Hmean and run length matrix in the same ROI (r = -0.04 to 0.52, NS). Co-occurrence matrix and run length matrix in the same ROI were highly correlated (r = 0.90 to 0.99, p < 0.0001). Univariate analysis with the failure load revealed significant correlation only with BMD results, not texture parameters. Multiple regression analysis showed that the best predictors of failure load were BMD, Hmean, and run length matrix at the femoral neck, as well as age and sex, with an adjusted r (2) = 0.88. Added to femoral neck BMD, Hmean and run length matrix at the femoral neck (without the effect of age and sex) improved failure load prediction (compared to femoral neck BMD alone) from adjusted r (2) = 0.67 to adjusted r (2) = 0.84. Our results suggest that bone texture measurement improves failure load prediction when added to BMD.

An in vivo comparison of hip structure analysis (HSA) with measurements obtained by QCT

SummaryIn a population of elderly women, bone cross-sectional area (CSA), cross-sectional moment of inertia (CSMI), section modulus (Z), femoral neck axis length (FNAL), and width measured with hip structure analysis (HSA) on dual-energy x-ray absorptiometry (DXA) images in the femoral neck and trochanteric regions are highly correlated to quantitative computed tomography (QCT) measurements.IntroductionHSA is a method of obtaining measurements of proximal femur structure using 2D DXA technology. This study was designed to examine the correlations between HSA measurements and 3D QCT.MethodsForty-one women (mean age, 82.8 ± 2.5 years) were measured using DXA and a 64-slice CT scanner (1 mm slice thickness, 0.29 mm in plane resolution). HSA parameters were calculated at the narrow neck (NN) and trochanteric (IT) regions on the DXA image. These regions were then translated to anatomically equivalent regions on the QCT dataset by co-registering the DXA image and QCT dataset using four DXA images acquired at different angles.ResultsAt the NN and IT regions, high linear correlations were measured between HSA and QCT for CSA r = 0.95 and 0.93, CSMI r = 0.94 and 0.93, and Z r = 0.93 and 0.89, respectively. All correlations were highly significant (p < 0.001), but there were differences in slope and offset between the two techniques, at least in part due to differences in calibration between the two techniques. FNAL and width of the bone at the NN and IT regions, physical measurements independent of the calibration, were highly correlated (r = 0.90–0.95, p < 0.001) and had slopes close to 1.0 (range, 0.978 to 1.003).ConclusionCSA, CSMI, Z, FNAL, and width measured by HSA correlate highly to high-resolution QCT.

On the Interpretation of Rat Carcinogenicity Studies for Human PTH(1-34) and Human PTH(1-84)

On the Interpretation of Rat Carcinogenicity Studies for Human PTH(1-34) and Human PTH(1-84)

Densitometric, morphometric and mechanical distributions in the human proximal femur

With the prevalent use of DXA-measured BMD to assess pathologic hip fractures and its recently reported lack of reliability to predict fracture or account for efficacy of anti-resorptive therapy, it is reasonable to assess whether variations in the primary and secondary tensile and compressive trabecular microstructure can account for variations in proximal femur strength in comparison to DXA-measured BMD. To that end, microstructural and densitometric measures of trabecular bone specimens, from discrete sites within the proximal femur, were correlated with their mechanical properties. We hypothesize that accounting for regional variations in trabecular microstructure will improve predictions of proximal femur strength and stiffness compared to bone density measured by DXA. Forty-seven samples (seven donors) from seven distinct sites of human proximal femur underwent DXA and μCT imaging and mechanical testing. The results revealed significant variations in BMC, morphometric indices and mechanical properties within the proximal femur. This work has demonstrated that the mechanical performance of each sub-region is highly dependent on the corresponding trabecular microstructure. BMD measured by DXA at standard regions of interest cannot resolve the variations in trabecular density and microstructure that govern the mechanical behavior of the proximal femur. This work suggests that a quantitative Singh index that uses high resolution QCT to monitor the trabecular microstructure at specific sub-regions of the proximal femur may allow better predictions of hip fracture risk in individual patients and an improved assessment of changing bone structure in response to pharmacological interventions.

Microstructural insight into pedestrian pelvic fracture as assessed by high-resolution computed tomography

Pelvic and femoral neck bone surface strains were recorded in five full-body human cadaver vehicle–pedestrian impacts. Impacts were performed at 40 km/h using automotive front ends constructed to represent those used in previously reported finite element simulations. While experimental kinematics and bone strains closely matched model predictions, observed pelvic fractures did not consistently agree with the model, and could not be solely explained by vehicle geometry. In an attempt to reconcile injury outcome with factors apart from vehicle design, a proxy measure of subject skeletal health was assessed by high-resolution quantitative computed tomography (HRqCT) of the femoral neck. The incidence of hip/pelvis fracture was found to be consistent with low volumetric bone mineral density and low trabecular bone density. This finding lends quantitative support to the notion that healthy trabecular architecture is crucial in withstanding non-physiological impact loads. Furthermore, it is recommended that injury criteria used to assess vehicle safety with regard to pedestrians consider the increased susceptibility of elderly victims to pelvic fracture.