Benchtop proof of concept and comparison of iron- and magnesium-based bioresorbable flow diverters.

OBJECTIVE: Bioresorbable flow diverters (BRFDs) could significantly improve the performance of next-generation flow diverter technology. In the current work, magnesium and iron alloy BRFDs were prototyped and compared in terms of porosity/pore density, radial strength, flow diversion functionality, and resorption kinetics to offer insights into selecting the best available bioresorbable metal candidate for the BRFD application. METHODS: BRFDs were constructed with braided wires made from alloys of magnesium (MgBRFD) or iron (FeBRFD). Pore density and crush resistance force were measured using established methods. BRFDs were deployed in silicone aneurysm models attached to flow loops to investigate flow diversion functionality and resorption kinetics in a simulated physiological environment. RESULTS: The FeBRFD exhibited higher pore density (9.9 vs 4.3 pores/mm2) and crush resistance force (0.69 ± 0.05 vs 0.53 ± 0.05 N/cm, p = 0.0765, n = 3 per group) than the MgBRFD, although both crush resistances were within the range previously reported for FDA-approved flow diverters. The FeBRFD demonstrated greater flow diversion functionality than the MgBRFD, with significantly higher values of established flow diversion metrics (mean transit time 159.6 ± 11.9 vs 110.9 ± 1.6, p = 0.015; inverse washout slope 192.5 ± 9.0 vs 116.5 ± 1.5, p = 0.001; n = 3 per group; both metrics expressed as a percentage of the control condition). Last, the FeBRFD was able to maintain its braided structure for > 12 weeks, whereas the MgBRFD was almost completely resorbed after 5 weeks. CONCLUSIONS: The results of this study demonstrated the ability to manufacture BRFDs with magnesium and iron alloys. The data suggest that the iron alloy is the superior material candidate for the BRFD application due to its higher mechanical strength and lower resorption rate relative to the magnesium alloy.

Bioresorbable flow diverters for the treatment of intracranial aneurysms: review of current literature and future directions.

The use of flow diverters is a rapidly growing endovascular approach for the treatment of intracranial aneurysms. All FDA-approved flow diverters are composed of nitinol or cobalt-chromium, which will remain in the patient for the duration of their life. Bioresorbable flow diverters have been proposed by several independent investigators as the next generation of flow diverting devices. These devices aim to serve their transient function of occluding and healing the aneurysm prior to being safely resorbed by the body, eliminating complications associated with the permanent presence of conventional flow diverters. Theoretical advantages of bioresorbable flow diverters include (1) reduction in device-induced thrombosis; (2) reduction in chronic inflammation and device-induced stenosis; (3) reduction in side branch occlusion; (4) restoration of physiological vasomotor function; (5) reduction in imaging artifacts; and (6) use in pediatric applications. Advances made in the similar bioresorbable coronary stenting field highlight some of these advantages and demonstrate the feasibility and safety of bioresorbable endovascular devices in the clinic. The current work aims to review the progress of bioresorbable flow diverters, identify opportunities for further investigation, and ultimately stimulate the advancement of this technology.

Improved biocompatibility of Zn-Ag-based stent materials by microstructure refinement.

The metallurgical engineering of bioresorbable zinc (Zn)-based medical alloys would greatly benefit from clarification of the relationships between material properties and biological responses. Here we investigate the biocompatibility of three Zn-based silver (Ag)-containing alloys, ranging from binary to quinary alloy systems. Selected binary and quinary Zn-Ag-based alloys underwent solution treatment (ST) to increase the solubility of Ag-rich phases within the Zn bulk matrix, yielding two different microstructures (one without ST and a different one with ST) with the same elemental composition. This experimental design was intended to clarify the relationship between elemental profile/microstructure and biocompatibility for the Zn-Ag system. We found that the quinary alloy system (Zn-4Ag-0.8Cu-0.6Mn-0.15Zr) performed significantly better, in terms of histomorphometry, than any alloy system we have evaluated to date. Furthermore, when solution treated to increase strength and ductility and reduce the fraction of Ag-rich phases, the quinary alloy's biocompatibility further improved. In vitro corrosion testing and metallographic analysis of in vivo implants demonstrated a more uniform mode of corrosion for the solution treated alloy. We conclude that Zn-Ag alloys can be engineered through alloying to substantially reduce neointimal growth. The positive effect on neointimal growth can be further enhanced by dissolving the AgZn3 precipitates in the Zn matrix to improve the corrosion uniformity. These findings demonstrate that neointimal-forming cells can be regulated by elemental additions and microstructural changes in degradable Zn-based implant materials. STATEMENT OF SIGNIFICANCE: The metallurgical engineering of bioresorbable zinc (Zn)-based medical alloys would greatly benefit from clarification of the relationships between material properties and biological responses. Here, selected binary and quinary Zn-Ag-based alloys underwent solution treatment (ST) to increase the solubility of Ag-rich phases within the Zn bulk matrix, yielding two different microstructures (one without ST and a different one with ST) with the same elemental composition. We found that applying a thermal treatment restores mechanical strength and mitigates the strain rate sensitivity of Zn-Ag alloys by dissolving AgZn3 precipitates. Ag-rich nano-precipitates in Zn decrease biocompatibility, a phenomenon that can be counteracted by dissolving the AgZn3 precipitates in the bulk Zn matrix.

Finite element analysis in clinical patients with atherosclerosis.

Endovascular plaque composition is strongly related to stent strut stress and is responsible for strut fatigue, stent failure, and possible in-stent restenosis. To evaluate the effect of plaque on artery wall resistance to expansion we performed in silico analysis of atherosclerotic vessels. We generated finite element models from in vivo intravascular ultrasound virtual histology images to determine local artery surface stiffness and determined which plaque structures have the greatest influence. We validated the predictive capacity of our modeling approach by testing an atherosclerotic peripheral artery ex vivo with pressure-inflation testing at physiological pressures ranging from 10 to 200 mmHg. For this purpose, the in silico deformation of the arterial wall was compared to that observed ex vivo. We found that calcification had a positive effect on surface stiffness with fibrous plaque and necrotic core having negative effects. Additionally, larger plaque structures demonstrated significantly higher average surface stiffness and calcification located nearer the lumen was also shown to increase surface stiffness. Therefore, more developed plaques will have greater resistance to expansion and higher stent strut stress, with calcification located near the lumen further increasing stress in localized areas. Thus, it may be expected that such plaque structures may increase the likelihood of localized stent strut fracture.

Numerical wave speed sensitivity study for assessment of myocardial elasticity in a simplified linear elastic and isotropic left ventricle model.

Since tissue elasticity can change with pathology, noninvasive assessment of elasticity has received increasing attention. Emerging methods for assessing cardiac elasticity utilize either an external source to induce propagating shear waves or intrinsic longitudinal waves created by natural cardiac events such as left ventricle stretching that occurs due to atrial kick during late diastole. However, the effect of morphological variations that occur in diseased hearts on this longitudinal stretch wave and the corresponding estimate of elasticity is not well understood and is an active area of research. This study investigated the sensitivity of longitudinal wave speed to material properties and chamber geometry parameters through numerical simulations using a finite element model of a bullet-shaped chamber with homogeneous isotropic linear elastic material properties. A longitudinal impulse displacement was applied to the base edge of the model to investigate wave propagation from this boundary. Parametric studies were performed for variables of interest related to geometry and material properties. The wave speeds estimated from simulation results were used to determine wave speed sensitivity to each variable. Wave speed was found to be a strong function of material elasticity and a weak function of chamber geometry and viscous damping. Simulated wave speed as a function of elasticity was in good agreement with wave speeds determined from an analytical expression for longitudinal wave speed in elastic thin plates. These promising preliminary results increase our understanding of how these parameters affect intrinsic longitudinal wave speed and warrant future studies addressing the impact of patient-specific model geometry, material anisotropy and hyperelasticity, and boundary conditions on wave speed.

Morphological and Hemodynamic Changes during Cerebral Aneurysm Growth.

Computational fluid dynamics (CFD) has grown as a tool to help understand the hemodynamic properties related to the rupture of cerebral aneurysms. Few of these studies deal specifically with aneurysm growth and most only use a single time instance within the aneurysm growth history. The present retrospective study investigated four patient-specific aneurysms, once at initial diagnosis and then at follow-up, to analyze hemodynamic and morphological changes. Aneurysm geometries were segmented via the medical image processing software Mimics. The geometries were meshed and a computational fluid dynamics (CFD) analysis was performed using ANSYS. Results showed that major geometry bulk growth occurred in areas of low wall shear stress (WSS). Wall shape remodeling near neck impingement regions occurred in areas with large gradients of WSS and oscillatory shear index. This study found that growth occurred in areas where low WSS was accompanied by high velocity gradients between the aneurysm wall and large swirling flow structures. A new finding was that all cases showed an increase in kinetic energy from the first time point to the second, and this change in kinetic energy seems correlated to the change in aneurysm volume.

Evaluation of the role of peripheral artery plaque geometry and composition on stent performance.

Peripheral stent fracture is a major precursor to restenosis of femoral artery atherosclerosis that has been treated with stent implantation. In this work, we validate a workflow for performing in silico stenting on a patient specific peripheral artery with heterogeneous plaque structure. Six human cadaveric femoral arteries were imaged ex vivo using intravascular ultrasound virtual histology (IVUS-VH) to obtain baseline vessel geometry and plaque structure. The vessels were then stented and the imaging repeated to obtain the stented vessel lumen area. Finite element (FE) models were then constructed using the IVUS-VH images, where the material property constants for each finite element were calculated using the proportions of each plaque component in the element, as identified by the IVUS-VH images. A virtual stent was deployed in each FE model, and the model lumen area was calculated and compared to the experimental lumen area to validate the modeling approach. The model was then used to compare stent performance for heterogeneous and homogeneous artery models, to determine whether plaque geometry or composition had added effects on stent performance. We found that the simulated lumen areas were similar to the corresponding experimental values, despite using generic material constants. Additionally, the heterogeneous and homogeneous lumen areas were also similar, implying that plaque geometry is a stronger predictor of stent expansion performance than plaque composition. Comparing stent stress and strain for heterogeneous and homogeneous models, it was found that stress from these two models had a strong linear correlation, while the strain correlation was weaker but still present. This implies that stent performance may be predicted with a simple homogeneous material models accounting for overall geometry of the plaque, providing that stent fatigue is calculated using stress criteria.

Finite Element Analysis of the Septal Cartilage L-Strut.

Importance: Septoplasty is one of the most commonly performed operations in the head and neck. However, the reasons for septoplasty failure and the additional stress of performing a chondrotomy on the septal cartilage are not well understood. Design, Setting, and Participants: A finite element model of the nasal septum was created using a microcomputed tomography scan of the nasoseptal complex that was reconstructed into a three-dimensional model in silico. Testing included four common chondrotomy designs: traditional L-strut, double-cornered chondrotomy (DCC), curved L-strut, and the C-curve. Tip displacement was applied in a vector parallel to the caudal strut to simulate nasal tip palpation. Main Outcomes and Measures: With finite element analysis, the maximum principal stress (MPS), von Mises stress (VMS), harvested cartilage volume, and surface area were recorded. Results: The highest MPS for the L-strut, DCC, curved L-strut, and C-curve was identified at the corner of the chondrotomy. The MPS at the corner of the chondrotomy was reduced 44% when comparing the C-curve with the traditional L-strut. The VMS patterns showed compressive stress along the caudal septum in all models, but at the corner, the stresses were highest in the chondrotomies designed with sharp-angled corners. The VMS showed a 76% decrease when comparing the C-curve with the traditional L-strut. The stress across the anterior septal angle is also higher in models with sharp-angled corners. Cartilage harvest volumetric and surface area assessments did not show meaningful differences between shapes. Conclusions and Relevance: The highest area of stress is near the transition of the dorsal to caudal septum in all models. Stresses are relatively higher in chondrotomy shapes that contain sharp-angled corners. The relative reduction in MPS and VMS utilizing a C-curve instead of an L-strut may decrease the likelihood that the septum will deform or fail in this region. The volume and surface area of the C-curve are similar to that of the L-strut technique. Avoiding sharp-angled corners reduces the stresses at the corner of the chondrotomy and across the anterior septal angle. Using a C-curve may be an improved septoplasty design.

In vitro Remote Aspiration Embolectomy for the Treatment of Acute Ischemic Stroke.

BACKGROUND: "Remote aspiration," using suction from the proximal internal carotid artery (ICA) to open terminus occlusions, has been reported in small case series. However, it remains unclear whether remote aspiration is feasible for middle cerebral artery occlusions in the setting of potential inflow from communicating arteries. We performed an in vitro study to assess whether suction applied at various locations proximal to an occlusion could successfully aspirate the clot. METHODS: A glass model of 4 mm inner diameter (ID) with 1 mm distal narrowing and 2 mm side branch to simulate a communicating artery was constructed. A proximal side branch was placed to simulate inflow from the proximal ICA. The impact of three different-sized catheters (ID 0.088, 0.070, and 0.056 in) on histologically different (red blood cell-cell rich, fibrin-rich, and mixed) clot analogues was tested with the catheter tip placed remotely either distal or proximal to the collateral branch. Aspiration was attempted with (1) open system (flow in both the ICA and the collateral branch, (2) flow arrest with open collateral (no flow in the ICA, but flow in the collateral branch), and (3) closed system (no flow in either the ICA or the collateral branch). The outcome was success or failure of remote aspiration. RESULTS: For the 0.088-in catheter, remote aspiration was successful in all conditions. For the 0.070-in catheter, remote aspiration was unsuccessful without proximal flow arrest, but was successful in all other scenarios. For the 0.056-in catheter, remote aspiration was successful only with complete flow arrest. CONCLUSIONS: In a noncollapsible system, remote aspiration can be successfully achieved even in the setting of prominent branch arteries by using relatively large aspiration catheters. Proximal flow arrest may facilitate successful remote aspiration for some catheter sizes.

Patient specific characterization of artery and plaque material properties in peripheral artery disease.

Patient-specific finite element (FE) modeling of atherosclerotic plaque is challenging, as there is limited information available clinically to characterize plaque components. This study proposes that for the limited data available in vivo, material properties of plaque and artery can be identified using inverse FE analysis and either a simple neo-Hookean constitutive model or assuming linear elasticity provides sufficient accuracy to capture the changes in vessel deformation, which is the available clinical metric. To test this, 10 human cadaveric femoral arteries were each pressurized ex vivo at 6 pressure levels, while intravascular ultrasound (IVUS) and virtual histology (VH) imaging were performed during controlled pull-back to determine vessel geometry and plaque structure. The VH images were then utilized to construct FE models with heterogeneous material properties corresponding to the vessel plaque components. The constitutive models were then fit to each plaque component by minimizing the difference between the experimental and the simulated geometry using the inverse FE method. Additionally, we further simplified the analysis by assuming the vessel wall had a homogeneous structure, i.e. lumping artery and plaque as one tissue. We found that for the heterogeneous wall structure, the simulated and experimental vessel geometries compared well when the fitted neo-Hookean parameters or elastic modulus, in the case of linear elasticity, were utilized. Furthermore, taking the median of these fitted parameters then inputting these as plaque component mechanical properties in the finite element simulation yielded differences between simulated and experimental geometries that were on average around 2% greater (1.30-5.55% error range to 2.33-11.71% error range). For the homogeneous wall structure the simulated and experimental wall geometries had an average difference of around 4% although when the difference was calculated using the median fitted value this difference was larger than for the heterogeneous fits. Finally, comparison to uniaxial tension data and to literature constitutive models also gave confidence to the suitability of this simplified approach for patient-specific arterial simulation based on data that may be acquired in the clinic.

Mechanical testing setups affect spine segment fracture outcomes.

The purpose of the work presented here was to establish an experimental testing configuration that would generate a bending compression fracture in a laboratory setting. To this end, we designed and fabricated a fixture to accommodate a three level spine segment and to be able to perform mechanical testing by applying an off-centric compressive loading to create a flexion-type motion. Forces and moments occurring during testing were measured with a six-channel load cell. The initial testing configuration (Fixture A) included plates connected to the superior potted vertebral body and to the ball-socket joint of the testing system ram. Surprisingly, while all cadaveric specimens underwent a similar off-centric compressive loading, most of the specimens showed extension outcomes as opposed to the intended pure-flexion motion. The extension was due to fixture size and weight; by applying an off-centric load directly on the top plate, unintended large shear forces were generated. To resolve the issue, several modifications were made to the original fixture configuration. These modifications included the removal of the superior plates and the implementation of wedges at the superior surface of the fixture (Fixture B). A synthetic sample was used during this modification phase to minimize the number of cadaveric specimens while optimizing the process. The best outcomes were consistently observed when a 15°-wedge was used to provide flexion-type loading. Cadaveric specimens were then experimentally tested to fracture using the modified testing configuration (Fixture B). A comparison between both fixtures, A and B, revealed that almost all biomechanical parameters, including force, moment, and displacement data, were affected by the testing setup. These results suggest that fixture design and implementation for testing is of extreme importance, and can influence the fracture properties and affect the intended motion.

Multiple Aneurysms AnaTomy CHallenge 2018 (MATCH)-phase II: rupture risk assessment.

PURPOSE: Assessing the rupture probability of intracranial aneurysms (IAs) remains challenging. Therefore, hemodynamic simulations are increasingly applied toward supporting physicians during treatment planning. However, due to several assumptions, the clinical acceptance of these methods remains limited. METHODS: To provide an overview of state-of-the-art blood flow simulation capabilities, the Multiple Aneurysms AnaTomy CHallenge 2018 (MATCH) was conducted. Seventeen research groups from all over the world performed segmentations and hemodynamic simulations to identify the ruptured aneurysm in a patient harboring five IAs. Although simulation setups revealed good similarity, clear differences exist with respect to the analysis of aneurysm shape and blood flow results. Most groups (12/71%) included morphological and hemodynamic parameters in their analysis, with aspect ratio and wall shear stress as the most popular candidates, respectively. RESULTS: The majority of groups (7/41%) selected the largest aneurysm as being the ruptured one. Four (24%) of the participating groups were able to correctly select the ruptured aneurysm, while three groups (18%) ranked the ruptured aneurysm as the second most probable. Successful selections were based on the integration of clinically relevant information such as the aneurysm site, as well as advanced rupture probability models considering multiple parameters. Additionally, flow characteristics such as the quantification of inflow jets and the identification of multiple vortices led to correct predictions. CONCLUSIONS: MATCH compares state-of-the-art image-based blood flow simulation approaches to assess the rupture risk of IAs. Furthermore, this challenge highlights the importance of multivariate analyses by combining clinically relevant metadata with advanced morphological and hemodynamic quantification.

Optimizing Accuracy of Proximal Femur Elastic Modulus Equations.

Quantitative computed tomography-based finite element analysis (QCT/FEA) is a promising tool to predict femoral properties. One of the modeling parameters required as input for QCT/FEA is the elastic modulus, which varies with the location-dependent bone mineral density (ash density). The aim of this study was to develop optimized equations for the femoral elastic modulus. An inverse QCT/FEA method was employed, using an optimization process to minimize the error between the predicted femoral stiffness values and experimental values. We determined optimal coefficients of an elastic modulus equation that was a function of ash density only, and also optimal coefficients for several other equations that included along with ash density combinations of the variables sex and age. All of the optimized models were found to be more accurate than models from the literature. It was found that the addition of the variables sex and age to ash density made very minor improvements in stiffness predictions compared to the model with ash density alone. Even though the addition of age did not remarkably improve the statistical metrics, the effect of age was reflected in the elastic modulus equations as a decline of about 9% over a 60-year interval.

Multiple Aneurysms AnaTomy CHallenge 2018 (MATCH): Phase I: Segmentation.

PURPOSE: Advanced morphology analysis and image-based hemodynamic simulations are increasingly used to assess the rupture risk of intracranial aneurysms (IAs). However, the accuracy of those results strongly depends on the quality of the vessel wall segmentation. METHODS: To evaluate state-of-the-art segmentation approaches, the Multiple Aneurysms AnaTomy CHallenge (MATCH) was announced. Participants carried out segmentation in three anonymized 3D DSA datasets (left and right anterior, posterior circulation) of a patient harboring five IAs. Qualitative and quantitative inter-group comparisons were carried out with respect to aneurysm volumes and ostia. Further, over- and undersegmentation were evaluated based on highly resolved 2D images. Finally, clinically relevant morphological parameters were calculated. RESULTS: Based on the contributions of 26 participating groups, the findings reveal that no consensus regarding segmentation software or underlying algorithms exists. Qualitative similarity of the aneurysm representations was obtained. However, inter-group differences occurred regarding the luminal surface quality, number of vessel branches considered, aneurysm volumes (up to 20%) and ostium surface areas (up to 30%). Further, a systematic oversegmentation of the 3D surfaces was observed with a difference of approximately 10% to the highly resolved 2D reference image. Particularly, the neck of the ruptured aneurysm was overrepresented by all groups except for one. Finally, morphology parameters (e.g., undulation and non-sphericity) varied up to 25%. CONCLUSIONS: MATCH provides an overview of segmentation methodologies for IAs and highlights the variability of surface reconstruction. Further, the study emphasizes the need for careful processing of initial segmentation results for a realistic assessment of clinically relevant morphological parameters.

Factors associated with proximal femur fracture determined in a large cadaveric cohort.

Many researchers have used cadaveric fracture tests to determine the relationship between proximal femur (hip) fracture strength and a multitude of possible explanatory variables, typically considered one or two at a time. These variables include subject-specific proximal femur variables such as femoral neck areal bone mineral density (aBMD), sex, age, and geometry, as well as physiological hip fracture event variables such as fall speed and angle of impact. However, to our knowledge, no study has included all of these variables simultaneously in the same experimental dataset. To address this gap, the present study simultaneously included all of these subject-specific and fracture event variables in multivariate models to understand their contributions to femoral strength and fracture type. The primary aim of this study was to determine not only whether each of these variables contributed to the prediction of femoral strength, but also to determine the relative importance of each variable in strength prediction. A secondary aim was to similarly characterize the importance of these variables for the prediction of fracture type. To accomplish these aims, we characterized 197 proximal femurs (covering a wide range of subject-specific variables) with DXA and CT scans, and then tested the femurs to fracture in a sideways fall on the hip configuration. Each femur was tested using one of three fall speed conditions and one of four angles of impact (bone orientations). During each test, we acquired measurements of relevant force and displacement data. We then reduced the test data to determine femoral strength, and we used post-fracture CT scans to classify the fracture type (e.g., trochanteric, cervical). Using these results, the explanatory variables were analyzed with mixed statistical models to explain variations in hip fracture strength and fracture type, respectively. Five explanatory variables were statistically significant in explaining the variability in femoral strength: aBMD, sex, age, fall speed, and neck-shaft angle (P ≤ 0.0135). These five variables, including significant interactions, explained 80% of the variability in hip fracture strength. Additionally, when only aBMD, sex, and age (P < 0.0001) were considered in the model, again including significant interactions, these three variables alone explained 79% of the variability in hip fracture strength. So while fall speed (P = 0.0135) and neck-shaft angle (P = 0.0041) were statistically significant, the inclusion of these variables did not appreciably improve the prediction of hip fracture strength compared to the model that considered only aBMD, sex and age. For the variables we included in this study, in the ranges we considered, our findings indicate that the clinically-available information of patient age, sex and aBMD are sufficient for femoral strength assessment. These findings also suggest that there is little value in the extra effort required to characterize the effect of femoral geometry on strength, or to account for the probabilistic nature of fall-related factors such as fall speed and angle of impact. For fracture type, the only explanatory variable found to be significant was aBMD (P ≤ 0.0099). We found that the odds of having intertrochanteric fractures increased by 47% when aBMD decreased by one standard deviation (0.2 g/cm2).

Are DXA/aBMD and QCT/FEA Stiffness and Strength Estimates Sensitive to Sex and Age?

Dual X-ray absorptiometry (DXA) measures areal bone mineral density (aBMD) by simplifying a complex 3D bone structure to a 2D projection and is not equally effective for explaining fracture strength in women and men. Unlike DXA, subject-specific quantitative computed tomography-based finite element analysis (QCT/FEA) estimates fracture strength using 3D bone mineral distribution and geometry. By using experimentally-measured femoral stiffness and strength from a one hundred sample cadaveric cohort that included variations in sex and age, we wanted to determine if QCT/FEA estimates were able to better predict the experimental variations than DXA/aBMD. For each femur, DXA/aBMD was assessed and a QCT/FEA model was developed to estimate femoral stiffness and strength. Then, the femur was mechanically tested to fracture in a sideways fall on the hip position to measure stiffness and strength. DXA/aBMD and QCT/FEA estimates were compared for their sensitivity to sex and age with multivariate statistical analyses. When comparing the measured data with DXA/aBMD predictions, both age and sex were significant (p ≤ 0.0398) for both femoral stiffness and strength. However, QCT/FEA predictions of stiffness and strength showed sex was insignificant (p ≥ 0.23). Age was still significant (p ≤ 0.0072). These results indicate that QCT/FEA, unlike DXA/aBMD, accounted for bone differences due to sex.