Is multidetector CT-based bone mineral density and quantitative bone microstructure assessment at the spine still feasible using ultra-low tube current and sparse sampling?

OBJECTIVE: Osteoporosis diagnosis using multidetector CT (MDCT) is limited to relatively high radiation exposure. We investigated the effect of simulated ultra-low-dose protocols on in-vivo bone mineral density (BMD) and quantitative trabecular bone assessment. MATERIALS AND METHODS: Institutional review board approval was obtained. Twelve subjects with osteoporotic vertebral fractures and 12 age- and gender-matched controls undergoing routine thoracic and abdominal MDCT were included (average effective dose: 10 mSv). Ultra-low radiation examinations were achieved by simulating lower tube currents and sparse samplings at 50%, 25% and 10% of the original dose. BMD and trabecular bone parameters were extracted in T10-L5. RESULTS: Except for BMD measurements in sparse sampling data, absolute values of all parameters derived from ultra-low-dose data were significantly different from those derived from original dose images (p<0.05). BMD, apparent bone fraction and trabecular thickness were still consistently lower in subjects with than in those without fractures (p<0.05). CONCLUSION: In ultra-low-dose scans, BMD and microstructure parameters were able to differentiate subjects with and without vertebral fractures, suggesting osteoporosis diagnosis is feasible. However, absolute values differed from original values. BMD from sparse sampling appeared to be more robust. This dose-dependency of parameters should be considered for future clinical use. KEY POINTS: • BMD and quantitative bone parameters are assessable in ultra-low-dose in vivo MDCT scans. • Bone mineral density does not change significantly when sparse sampling is applied. • Quantitative trabecular bone microstructure measurements are sensitive to dose reduction. • Osteoporosis subjects could be differentiated even at 10% of original dose. • Radiation exposure should be considered when comparing quantitative bone parameters.

In Vivo Precision of Digital Topological Skeletonization Based Individual Trabecula Segmentation (ITS) Analysis of Trabecular Microstructure at the Distal Radius and Tibia by HR-pQCT.

Trabecular plate and rod microstructure plays a dominant role in the apparent mechanical properties of trabecular bone. With high-resolution computed tomography (CT) images, digital topological analysis (DTA) including skeletonization and topological classification was applied to transform the trabecular three-dimensional (3D) network into surface and curve skeletons. Using the DTA-based topological analysis and a new reconstruction/recovery scheme, individual trabecula segmentation (ITS) was developed to segment individual trabecular plates and rods and quantify the trabecular plate- and rod-related morphological parameters. High-resolution peripheral quantitative computed tomography (HR-pQCT) is an emerging in vivo imaging technique to visualize 3D bone microstructure. Based on HR-pQCT images, ITS was applied to various HR-pQCT datasets to examine trabecular plate- and rod-related microstructure and has demonstrated great potential in cross-sectional and longitudinal clinical applications. However, the reproducibility of ITS has not been fully determined. The aim of the current study is to quantify the precision errors of ITS plate-rod microstructural parameters. In addition, we utilized three different frequently used contour techniques to separate trabecular and cortical bone and to evaluate their effect on ITS measurements. Overall, good reproducibility was found for the standard HR-pQCT parameters with precision errors for volumetric BMD and bone size between 0.2%-2.0%, and trabecular bone microstructure between 4.9%-6.7% at the radius and tibia. High reproducibility was also achieved for ITS measurements using all three different contour techniques. For example, using automatic contour technology, low precision errors were found for plate and rod trabecular number (pTb.N, rTb.N, 0.9% and 3.6%), plate and rod trabecular thickness (pTb.Th, rTb.Th, 0.6% and 1.7%), plate trabecular surface (pTb.S, 3.4%), rod trabecular length (rTb.ℓ, 0.8%), and plate-plate junction density (P-P Junc.D, 2.3%) at the tibia. The precision errors at the radius were similar to those at the tibia. In addition, precision errors were affected by the contour technique. At the tibia, precision error by the manual contour method was significantly different from automatic and standard contour methods for pTb.N, rTb.N and rTb.Th. Precision error using the manual contour method was also significantly different from the standard contour method for rod trabecular number (rTb.N), rod trabecular thickness (rTb.Th), rod-rod and plate-rod junction densities (R-R Junc.D and P-R Junc.D) at the tibia. At the radius, the precision error was similar between the three different contour methods. Image quality was also found to significantly affect the ITS reproducibility. We concluded that ITS parameters are highly reproducible, giving assurance that future cross-sectional and longitudinal clinical HR-pQCT studies are feasible in the context of limited sample sizes.

Evaluation of Trabecular Microstructure of Cancellous Bone Using Quarter-Detector Computed Tomography.

Quarter-detector computed tomography (QDCT) is an ultra-high-spatial-resolution imaging technique. This study aimed to verify the validity of trabecular structure evaluation using a QDCT scanner in the diagnosis of osteoporosis. We used a cancellous bone specimen image of the second lumbar vertebrae of an adult male with moderate osteoporosis. To obtain QDCT images, we created a three-dimensional model from micro-CT images of the specimen. Statistical analysis was performed on the relationship between micro-CT and QDCT imaging modalities. The differences between micro-CT and QDCT were assessed based on their significance with respect to the calculated mean measurements using the Mann-Whitney test. Single regression analysis was performed using linear regression, with micro-CT and QDCT as the explanatory and objective variables, respectively, to determine the relationship of the measured values between the two modalities. By applying the necessary correction to the micro-CT measured values, it is possible to perform an analysis equivalent to micro-CT, which offers higher spatial resolution than QDCT. We found evidence that if QDCT can be used, trabecular structure evaluation may contribute to image diagnosis to evaluate practical bone fragility.

Six-minute, in vivo MRI quantification of proximal femur trabecular bone 3D microstructure.

BACKGROUND: Assessment of proximal femur trabecular bone microstructure in vivo by magnetic resonance imaging has recently been validated for acquiring information independent of bone mineral density in osteoporotic patients. However, the requisite signal-to-noise ratio (SNR) and resolution for interrogation of the trabecular microstructure at this anatomical location prolongs the scan duration and renders the imaging protocol clinically infeasible. Parallel imaging and compressed sensing (PICS) techniques can reduce the scan duration of the imaging protocol without substantially compromising image quality. The present work investigates the limits of acceleration for a commonly used PICS technique, ℓ1-ESPIRiT, for the purpose of quantifying measures of trabecular bone microarchitecture. Based on a desired error tolerance, a six-minute, prospectively accelerated variant of the imaging protocol was developed and assessed for intersession reproducibility and agreement with the longer reference scan. PURPOSE: To investigate the limits of acceleration for MRI-based trabecular bone quantification by parallel imaging and compressed sensing reconstruction, and to develop a prototypical imaging protocol for assessing the proximal femur microstructure in a clinically practical scan time. METHODS: Healthy participants (n = 11) were scanned by a 3D balanced steady-state free precession (bSSFP) sequence satisfying the Nyquist criterion with a scan duration of about 18 min. The raw data were retrospectively undersampled and reconstructed to mimic various acceleration factors ranging from 2 to 6. Trabecular volumes-of-interest in four major femoral regions (greater trochanter, intertrochanteric region, femoral neck, and femoral head) were analyzed and six relevant measures of trabecular bone microarchitecture (bone volume fraction, surface-to-curve ratio, erosion index, elastic modulus, trabecular thickness, plates-to-rods ratio) were obtained for images of all accelerations. To assess agreement, median percent error and intraclass correlation coefficients (ICCs) were computed using the fully-sampled data as reference. Based on this analysis, a prospectively 3-fold accelerated sequence with a duration of about 6 min was developed and the analysis was repeated. RESULTS: A prospective acceleration factor of 3 demonstrated comparable performance in reproducibility and absolute agreement to the fully-sampled scan. The median CoV over all image-derived metrics was generally <6 % and ICCs >0.70. Also, measurements from prospectively 3-fold accelerated scans demonstrated in general median percent errors of <7 % and ICCs >0.70. CONCLUSION: The present work proposes a method to make in vivo quantitative assessment of proximal femur trabecular microstructure with a clinically practical scan duration of about 6 min.

Influence of processing parameters on mechanical properties of a 3D-printed trabecular bone microstructure.

Natural bone microstructure has shown to be the most efficient choice for the bone scaffold design. However, there are several process parameters involved in the generation of a microCT-based 3D-printed (3DP) bone. In this study, the effect of selected parameters on the reproducibility of mechanical properties of a 3DP trabecular bone structure is investigated. MicroCT images of a distal radial sample were used to reconstruct a 3D ROI of trabecular bone. Nine tensile tests on bulk material and 54 compression tests on 8.2 mm cubic samples were performed (9 cases × 6 specimens/case). The effect of input-image resolution, STL mesh decimation, boundary condition, support material, and repetition parameters on the weight, elastic modulus, and strength were studied. The elastic modulus and the strength of bulk material showed consistent results (CV% = 9 and 6%, respectively). The weight, elastic modulus, and strength of the cubic samples showed small intragroup variation (average CV% = 1.2, 9, and 5.5%, respectively). All studied parameters had a significant effect on the outcome variables with less effect on the weight. Utmost care to every step of the 3DP process and involved parameters is required to be able to reach the desired mechanical properties in the final printed specimen. © 2019 The Authors. Journal of Biomedical Materials Research Part B: Applied Biomaterials published by Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 108B:38-47, 2020.

Characterising variability and regional correlations of microstructure and mechanical competence of human tibial trabecular bone: An in-vivo HR-pQCT study.

OBJECTIVE: Quantifying spatial distribution of trabecular bone mechanical competence and microstructure is important for early diagnosis of skeletal disorders and potential risk of fracture. The objective of this study was to determine a spatial distribution of trabecular mechanical and morphological properties in human distal tibia and examine the contribution of regional variability of trabecular microarchitecture to mechanical competence. METHODS: A total of 340 representative volume elements at five anatomic regions of trabecular bone - anterior, posterior, lateral, medial and centre - from ten white European-origin postmenopausal women were studied. Region-specific trabecular parameters such as trabecular volume fraction, trabecular thickness, trabecular number, trabecular surface area, trabecular separation, plate-like structure fraction and finite element analysis of trabecular stiffness were determined based on in-vivo high resolution peripheral quantitative computed tomographic (HR-pQCT) images of distal tibiae from ten postmenopausal women. Mean values were compared using analysis of variance. The correlations between morphological parameters and stiffness were calculated. RESULTS: Significant regional variation in trabecular microarchitecture of the human distal tibia was observed (p < 0.05), with up to 106% differences between lowest (central and anterior) and highest (medial and posterior) regions. Higher proportion of plate-like trabecular morphology (63% and 53%) was found in medial and posterior regions in the distal tibia. Stiffness estimated from finite element models also differed significantly (p < 0.05), with stiffness being 4.5 times higher in the highest (medial) than lowest (central) regions. The bone volume fraction was the strongest correlate of stiffness in all regions. CONCLUSION: A novel finding of this study is the fact that significant regional variation of stiffness derived from two-phased FEA model with individual trabecula representation correlated highly to regional morphology obtained from in-vivo HR-pQCT images at the distal tibia. The correlations between regional morphological parameters and mechanical competence of trabecular bone were consistent at all regions studied, with regional BV/TV showing the highest correlation. The method developed for regional analysis of trabecular mechanical competence may offer a better insight into the relationship between mechanical behaviour and microstructure of bone. The findings provide evidence needed to further justify a larger-cohort feasibility study for early detection of bone degenerative diseases: examining regional variations in mechanical competence and trabecular specifications may allow better understanding of fracture risks in addition to others contributing factors.

Comparison of HR-pQCT- and microCT-based finite element models for the estimation of the mechanical properties of the calcaneus trabecular bone.

The calcaneus bone is formed of extensive trabecular bone and is therefore well suited to be used as an example of loaded bone to establish the ability of combining microfinite element (microFE) technique with high-resolution peripheral quantitative computed tomography (HR-pQCT) in determining its mechanical properties. HR-pQCT is increasingly used as a tool for in vivo bone clinical research, but its use has been limited to the distal radius and tibia. The goal of this study was to determine the applicability of HR-pQCT-derived microFE models of the calcaneus trabecular bone with 82 µm voxel size with reference to higher-resolution microCT-based models taken as gold standard. By comparing the outputs of microFE models generated from both HR-pQCT and microCT images of the trabecular bone of five calcaneus cadaveric specimens, it was found that the HR-pQCT-based models predicted mechanical properties for fracture load, total reaction force and von Mises stress are considerably different from microCT-based counterparts by 33, 64 and 70%, respectively. Also, the morphological analysis showed a comprehensive geometrical difference between HR-pQCT-based microFE models and their microCT-based equivalents. The results of the HR-pQCT-based models were found to have strong dependency on the threshold value chosen to binarise the images prior to finite element modelling. In addition, it was found that the voxel size has a strong impact on accuracy of imaged-based microFE models compared to other factors such as the presence of soft tissue and image scanning integration time. Therefore, although HR-pQCT has shown to be useful to predict overall structural and biomechanical changes, it is limited in providing local accurate biomechanical properties of trabecular bone and therefore should be used with caution when assessing bone remodelling through local changes of trabecular bone apposition and resorption in disease treatment monitoring.

Simplified boundary conditions alter cortical-trabecular load sharing at the distal radius; A multiscale finite element analysis.

High-resolution peripheral quantitative computed tomography (HR-pQCT) derived micro-finite element (FE) modeling is used to evaluate mechanical behavior at the distal radius microstructure. However, these analyses typically simulate non-physiologic simplified platen-compression boundary conditions on a small section of the distal radius. Cortical and trabecular regions contribute uniquely to distal radius mechanical behavior, and various factors affect these regions distinctly. Generalized strength predictions from standardized platen-compression analyses may not adequately capture region specific responses in bone. Our goal was to compare load sharing within the cortical-trabecular compartments between the standardized platen-compression BC simulations, and physiologic BC simulations using a validated multiscale approach. Clinical- and high-resolution images were acquired from nine cadaveric forearm specimens using an HR-pQCT scanner. Multiscale FE models simulating physiologic BCs, and micro-FE only models simulating platen-compression BCs were created for each specimen. Cortical and trabecular loads (N) along the length of the distal radius micro-FE section were compared between BCs using correlations. Principal strain distributions were also compared quantitatively. Cortical and trabecular loads from the platen-compression BC simulations were strongly correlated to the physiologic BC simulations. However, a 30% difference in cortical loads distally, and a 53% difference in trabecular loads proximally was observed under platen BC simulations. Also, distribution of principal strains was clearly different. Our data indicated that platen-compression BC simulations alter cortical-trabecular load sharing. Therefore, results from these analyses should be interpreted in the appropriate mechanical context for clinical evaluations of normal and pathologic mechanical behavior at the distal radius.

Validation of calcaneus trabecular microstructure measurements by HR-pQCT.

OBJECTIVE: Assessment of calcaneus microstructure using high-resolution peripheral quantitative computed tomography (HR-pQCT) might be used to improve fracture risk predictions or to assess responses to pharmacological and physical interventions. To develop a standard clinical protocol for the calcaneus, we validated calcaneus trabecular microstructure measured by HR-pQCT against 'gold-standard' micro-CT measurements. METHODS: Ten human cadaveric feet were scanned in situ using HR-pQCT (isotropic 82µm voxel size) at 100, 150 and 200ms integration times, and at 100ms integration time following removal of the calcaneus from the foot (ex vivo). Dissected portions of these bones were scanned using micro-computed tomography (micro-CT) at an isotropic 17.4µm voxel size. HR-pQCT images were rigidly registered to those obtained with micro-CT and divided into multiple 5mm sided cubes to evaluate and compare morphometric parameters between the modalities. Standard HR-pQCT measurements (derived bone volume fraction (BV/TVd); trabecular number, Tb.N; derived trabecular thickness, Tb.Thd; derived trabecular spacing, Tb.Spd) and corresponding micro-CT voxel-based measurements (BV/TV, Tb.N, Tb.Th, Tb.Sp) were compared. RESULTS: A total of 108 regions of interest were analysed across the 10 specimens. At all integration times HR-pQCT BV/TVd was strongly correlated with micro-CT BV/TV (r2=0.95-0.98, RMSE=1%), but BV/TVd was systematically lower than that measured by micro-CT (mean bias=5%). In contrast, HR-pQCT systematically overestimated Tb.N at all integration times; of the in situ scans, 200ms yielded the lowest mean bias and the strongest correlation with micro-CT (r2=0.61, RMSE=0.15mm-1). Regional analysis revealed greater accuracy for Tb.N in the superior regions of the calcaneus at all integration times in situ (mean bias=0.44-0.85mm-1; r2=0.70-0.88, p<0.001 versus mean bias=0.63-1.46mm-1; r2≤0.08, p≥0.21 for inferior regions). Tb.Spd was underestimated by HR-pQCT compared to micro-CT, but showed similar trends with integration time and the region evaluated as Tb.N. HR-pQCT Tb.Thd was also underestimated and moderately correlated (r2=0.53-0.59) with micro-CT Tb.Th, independently from the integration time. Stronger correlations, smaller biases and error were found in the scans of the calcaneus ex vivo compared to in situ. CONCLUSION: Calcaneus trabecular BV/TVd and trabecular microstructure, particularly in the superior region of the calcaneus, can be assessed by HR-pQCT. The highest integration time examined, 200ms, compared best with micro-CT. Weaker correlations for microstructure at inferior regions, and also with lower integration times, might limit the use of the proposed protocol, which warrants further investigation in vivo.

Robust Trabecular Microstructure in Type 2 Diabetes Revealed by Individual Trabecula Segmentation Analysis of HR-pQCT Images.

Type 2 diabetes (T2D) patients have an increased fracture risk, which may be partly explained by compromised bone microarchitecture within the cortical bone compartment. Data on trabecular bone parameters in T2D are contradictory. By high-resolution peripheral quantitative computed tomography (HR-pQCT), trabecular microarchitecture is preserved, yet larger trabecular holes are detected in T2D by MRI and DXA-based trabecular bone scores are abnormal. To determine if there are differences in trabecular microstructure, connectivity, and alignment in postmenopausal women with T2D as compared with controls, we performed an individual trabecula segmentation (ITS) analysis on HR-pQCT scans of the distal radius and tibia in 92 women with (n = 42) and without (n = 50) T2D. Unadjusted analyses showed that T2D subjects had greater total trabecular bone volume, trabecular plate volume fraction, plate number density, plate junction density, and axial alignment at the radius and tibia, and increased plate tissue fraction, but decreased rod tissue fraction and rod length at the radius (p < 0.05 for all). After adjustments for clinical covariates, plate number density and plate junction density remained higher at the radius and tibia, whereas total trabecular bone volume was increased and trabecular rod length was decreased at the radius. These differences remained significant after adjustment for hip BMD and trabecular volumetric bone density. Notably, the increased plate-like ITS qualities were seen in those with T2D duration of <10 years, whereas ITS parameters in subjects with T2D duration ≥10 years did not differ from those of control subjects. In conclusion, postmenopausal women with early T2D had a greater plate-like and less rod-like trabecular network. This early advantage in trabecular plate quality does not explain the well-established increased fracture risk in these patients and does not persist in the later stage of T2D. © 2018 American Society for Bone and Mineral Research.

Cranio-caudal asymmetries in trabecular architecture reflect vertebral fracture patterns.

Clinically, vertebral fractures often occur in the upper lumbar spine and involve the superior endplate of a vertebra (which is immediately caudal to a disc). Knowledge that the cranial endplate of a disc is thicker and has greater bone mineral density (BMD) than the corresponding caudal endplate helps to explain this phenomenon. In this study, we investigated structural differences in vertebral trabeculae on either side of a lumbar disc to provide further insight into vertebral fracture risk. As the focus is trabecular difference within a spinal motion segment, we define cranial and caudal vertebral trabeculae relative to the disc. Ninety-two spinal motion segments from 46 cadaveric lumbar spines (males, mean age 50years, range 21-63years) were studied. Disc narrowing on radiography and spread of barium sulfate (BaSO4) on discography were measured to indicate disc degeneration. Micro-computed tomography (µCT) images were obtained at a resolution of 82µm for each vertebra and processed to include only vertebral trabeculae. Using image processing, the vertebral trabeculae were divided into superior and inferior halves, and then into central and peripheral regions which were approximately opposite to the disc pulposus and annulus, and further into anterior and posterior sub-regions. Microarchitecture measurements for each vertebral region were obtained to determine the differences between the cranial and caudal trabeculae (relative to disc) and their associations with age and disc degeneration within each spinal motion segment. Data from the upper (L1/2-L3/4) and lower (L4/5) lumbar segments were analyzed separately. In the upper lumbar region, the trabeculae cranial to a disc on average had 5.3% greater BMD and trabecular bone volume, 3.6% greater trabecular number, 9.7% greater connectivity density, and 3.7% less trabecular separation than the corresponding caudal trabeculae (P<0.05 for all). Similar trends were observed in peripheral, anterior and posterior regions, but not in central region. No structural difference was observed in the trabeculae of L4/5 segment. Structural asymmetries of vertebral trabeculae were not associated with age, disc degeneration, or disc narrowing. Vertebral trabecular parameters cranial to the disc were greater than caudally in the upper but not in the lower lumbar region. Findings further explain why vertebral fractures are more common in the upper lumbar region and more frequently involve the endplate caudal to a disc.

Differences in Trabecular Microstructure Between Black and White Women Assessed by Individual Trabecular Segmentation Analysis of HR-pQCT Images.

Black women have lower fracture risk compared with white women, which may be partly explained by improved volumetric bone mineral density (vBMD) and bone microarchitecture primarily within the cortical bone compartment. To determine if there are differences in trabecular microstructure, connectivity, and alignment according to race/ethnicity, we performed individual trabecular segmentation (ITS) analyses on high-resolution peripheral quantitative computed tomography (HR-pQCT) scans of the distal radius and tibia in 273 peri- and postmenopausal black (n = 100) and white (n = 173) women participating in the Study of Women's Health Across the Nation in Boston. Unadjusted analyses showed that black women had greater trabecular plate volume fraction, plate thickness, plate number density, and plate surface area along with greater axial alignment of trabeculae, whereas white women had greater trabecular rod tissue fraction (p < 0.05 for all). Adjustment for clinical covariates augmented these race/ethnicity-related differences in plates and rods, such that white women had greater trabecular rod number density and rod-rod connectivity, whereas black women continued to have superior plate structural characteristics and axial alignment (p < 0.05 for all). These differences remained significant after adjustment for hip BMD and trabecular vBMD. In conclusion, black women had more plate-like trabecular morphology and higher axial alignment of trabeculae, whereas white women had more rod-like trabeculae. These differences may contribute to the improved bone strength and lower fracture risk observed in black women. © 2016 American Society for Bone and Mineral Research.

Minimizing Interpolation Bias and Precision Error in In Vivo µCT-Based Measurements of Bone Structure and Dynamics.

In vivo µCT imaging allows for high-resolution, longitudinal evaluation of bone properties. Based on this technology, several recent studies have developed in vivo dynamic bone histomorphometry techniques that utilize registered µCT images to identify regions of bone formation and resorption, allowing for longitudinal assessment of bone remodeling. However, this analysis requires a direct voxel-by-voxel subtraction between image pairs, necessitating rotation of the images into the same coordinate system, which introduces interpolation errors. We developed a novel image transformation scheme, matched-angle transformation (MAT), whereby the interpolation errors are minimized by equally rotating both the follow-up and baseline images instead of the standard of rotating one image while the other remains fixed. This new method greatly reduced interpolation biases caused by the standard transformation. Additionally, our study evaluated the reproducibility and precision of bone remodeling measurements made via in vivo dynamic bone histomorphometry. Although bone remodeling measurements showed moderate baseline noise, precision was adequate to measure physiologically relevant changes in bone remodeling, and measurements had relatively good reproducibility, with intra-class correlation coefficients of 0.75-0.95. This indicates that, when used in conjunction with MAT, in vivo dynamic histomorphometry provides a reliable assessment of bone remodeling.

X-ray-verified fractures are associated with finite element analysis-derived bone strength and trabecular microstructure in young adult men.

It has been suggested that fracture during childhood could be a predictor of low peak bone mass and thereby a potential risk factor for osteoporosis and fragility fractures later in life. The aim of this cross-sectional, population-based study was to investigate whether prevalent fractures, occurring from birth to young adulthood, were related to high-resolution peripheral quantitative computed tomography (HR-pQCT)-derived trabecular and cortical microstructure, as well as bone strength estimated by finite element (FEA) analysis of the radius and tibia in 833 young adult men around the time of peak bone mass (ages 23 to 25 years). In total, 292 subjects with prevalent X-ray-verified fractures were found. Men with prevalent fractures had lower trabecular bone volume fraction (BV/TV) at the radius (5.5%, p < 0.001) and tibia (3.7%, p < 0.001), as well as lower cortical thickness (5.1%, p < 0.01) and cortical cross-sectional area (4.1%, p < 0.01) at the tibia. No significant differences were seen for the cortical porosity or mean pore diameter. Using a logistic regression model (including age, smoking, physical activity, calcium intake, height, and weight as covariates), every SD decrease of FEA-estimated failure load was associated with an increased prevalence of fractures at both the radius (odds ratio [OR] 1.22 [1.03-1.45]) and tibia (OR 1.32 [1.11-1.56]). Including dual-energy X-ray absorptiometry (DXA)-derived radius areal bone mineral density (aBMD), cortical thickness, and trabecular BV/TV simultaneously in a logistic regression model (with age, smoking, physical activity, calcium intake, height, and weight as covariates), BV/TV was inversely and independently associated with prevalent fractures (OR 1.28 [1.04-1.59]), whereas aBMD and cortical thickness were not (OR 1.19 [0.92-1.55] and OR 0.91 [0.73-1.12], respectively). In conclusion, prevalent fractures in young adult men were associated with impaired trabecular BV/TV at the radius, independently of aBMD and cortical thickness, indicating that primarily trabecular bone deficits are of greatest importance for prevalent fracture in this population.