Comparison of trabecular bone density at vertebral and radial sites using quantitative computed tomography

Trabecular volumetric bone mineral density (VMD) was measured at the lumbar spine using quantitative computed tomography (QCT) and at the distal radius using peripheral QCT (pQCT) in 60 Japanese women aged 21–86 years. The age-dependent decrease between age 20 and 80 years was found to be almost identical between vertebral trabecular VMD and radial trabecular VMD, averaging 2.5±0.26 (SE) and 2.5±0.30 mg/cm³ per year, respectively. A highly significant correlation was found between vertebral and radial trabecular VMD (r=0.806,p<0.001) with a prediction error of ±9.6% (± SD/mean). In the present study, a relatively constant trabecular VMD ratio was found between the vertebral and distal radial sites, despite the relatively small study population. This may indicate a close parallelism between vertebral and radial trabecular bone.     

Multicenter precision of cortical and trabecular bone quality measures assessed by high‐resolution peripheral quantitative computed tomography

High‐resolution peripheral quantitative computed tomography (HR‐pQCT) has recently been introduced as a clinical research tool for in vivo assessment of bone quality. The utility of this technology to address important skeletal health questions requires translation to standardized multicenter data pools. Our goal was to evaluate the feasibility of pooling data in multicenter HR‐pQCT imaging trials. Reproducibility imaging experiments were performed using structure and composition‐realistic phantoms constructed from cadaveric radii. Single‐center precision was determined by repeat scanning over short‐term (<72 hours), intermediate‐term (3–5 months), and long‐term intervals (28 months). Multicenter precision was determined by imaging the phantoms at nine different HR‐pQCT centers. Least significant change (LSC) and root mean squared coefficient of variation (RMSCV) for each interval and across centers was calculated for bone density, geometry, microstructure, and biomechanical parameters. Single‐center short‐term RMSCVs were <1% for all parameters except cortical thickness (Ct.Th) (1.1%), spatial variability in cortical thickness (Ct.Th.SD) (2.6%), standard deviation of trabecular separation (Tb.Sp.SD) (1.8%), and porosity measures (6% to 8%). Intermediate‐term RMSCVs were generally not statistically different from short‐term values. Long‐term variability was significantly greater for all density measures (0.7% to 2.0%; p < 0.05 versus short‐term) and several structure measures: cortical thickness (Ct.Th) (3.4%; p < 0.01 versus short‐term), cortical porosity (Ct.Po) (15.4%; p < 0.01 versus short‐term), and trabecular thickness (Tb.Th) (2.2%; p < 0.01 versus short‐term). Multicenter RMSCVs were also significantly higher than short‐term values: 2% to 4% for density and micro–finite element analysis (µFE) measures (p < 0.0001), 2.6% to 5.3% for morphometric measures (p < 0.001), whereas Ct.Po was 16.2% (p < 0.001). In the absence of subject motion, multicenter precision errors for HR‐pQCT parameters were generally less than 5%. Phantom‐based multicenter precision was comparable to previously reported in in vivo single‐center precision errors, although this was approximately two to five times worse than ex vivo short‐term precision. The data generated from this study will contribute to the future design and validation of standardized procedures that are broadly translatable to multicenter study designs. © 2013 American Society for Bone and Mineral Research.     

Evaluation of orthogonal mechanical properties and density of human trabecular bone from the major metaphyseal regions with materials testing and computed tomography

We evaluated the orthogonal mechanical properties of human trabecular bone from the major metaphyseal regions with materials testing and quantitative computed tomography (CT). The proximal tibia, distal femur, proximal femur, distal radius, and proximal humerus from fresh cadaver specimens between the ages of 55 and 70 years were excised and prepared for experimentation. The bones were embedded and scanned at 1 or 1.5 mm intervals on a Technicare HPS 1440 and GE 9800 CT scanner. After scanning, the bones were sectioned, producing 8-mm cubes of trabecular bone which were mechanically tested in uniaxial compression at a strain rate of 1%. The testing sequence consisted of preyield tests in two of the three orthogonal directions and failure in the third. After testing, the cubes were evaluated for apparent density and ash weight. The results of the study show that the strength and stiffness of trabecular bone varies significantly within metaphyseal regions and from metaphysis to metaphysis. The power and significance of relationships between density and modulus varied as a function of metaphyseal location. Both linear and nonlinear models were significant, suggesting that trabecular deformation occurs in response to both axial and bending loads. Finally, the need for architectural measures of trabecular bone to predict mechanical properties is emphasized.     

Differentiating between orchiectomized rats and controls using measurements of trabecular bone density: A comparison among DXA,Histomorphometry, and peripheral quantitative computerized tomography

In studies of rat bone metabolism, trabecular bone density should be measured. Three established methods of measuring trabecular bone include trabecular bone volume by histomorphometry (BV/TV%), trabecular bone density by peripheral quantitative computerized tomography (pQCT), and areal bone density of trabecular-rich regions by dual x-ray absorptiometry (DXA). We compared the ability of these three methods to discriminate between orchiectomized (orchidectomized) rats and controls. Sixteen male Sprague-Dawley rats (400–425 g) were orchiectomized, and 16 others were controls. In vivo spine bone mineral density (BMD) was measured at the beginning of the study and again after 11 weeks. Rats were sacrificed, and ex vivo BMDs of the right femur and tibia were measured by DXA, followed by trabecular bone density of the right proximal tibia by pQCT. BV/TV% of the left proximal tibia was measured by histomorphometry. Differences between groups were detected by all three methods, but both the magnitude of the difference between groups and the variance of the measurements was much greater for histomorphometry and pQCT than for DXA. Consequently, the statistical significance for the difference between groups was comparable for all three methods. Of the sites measured with DXA, the proximal tibia had the greatest statistical significance for the difference between groups. In summary, all three methods can demonstrate the effect of orchiectomy on trabecular bone. The large differences between groups seen by histomorphometry are also seen by pQCT but not by DXA. We conclude that trabecular bone density by pQCT may be a reasonable surrogate for measurements by histomorphometry.Portions of the data presented here were presented at the 16th Annual Meeting of the American Society for Bone and Mineral Research, Kansas City, Missouri, September 30-September 9–13, 1994.     

High‐resolution peripheral quantitative computed tomography can assess microstructural and mechanical properties of human distal tibial bone

High‐resolution peripheral quantitative computed tomography (HR‐pQCT) is a newly developed in vivo clinical imaging modality. It can assess the 3D microstructure of cortical and trabecular bone at the distal radius and tibia and is suitable as an input for microstructural finite element (µFE) analysis to evaluate bone's mechanical competence. In order for microstructural and image‐based µFE analyses to become standard clinical tools, validation with a current gold standard, namely, high‐resolution micro‐computed tomography (µCT), is required. Microstructural measurements of 19 human cadaveric distal tibiae were performed for the registered HR‐pQCT and µCT images, respectively. Next, whole bone stiffness, trabecular bone stiffness, and elastic moduli of cubic subvolumes of trabecular bone in both HR‐pQCT and µCT images were determined by µFE analysis. The standard HR‐pQCT patient protocol measurements, derived bone volume fraction (BV/TV^d), trabecular number (Tb.N*), trabecular thickness (Tb.Th), trabecular spacing (Tb.Sp), and cortical thickness (Ct.Th), as well as the voxel‐based direct measurements, BV/TV, Tb.N*, Tb.Th*, Tb.Sp*, Ct.Th, bone surface‐to‐volume ratio (BS/BV), structure model index (SMI), and connectivity density (Conn.D), correlated well with their respective gold standards, and both contributed to µFE‐predicted mechanical properties in either single or multiple linear regressions. The mechanical measurements, although overestimated by HR‐pQCT, correlated highly with their gold standards. Moreover, elastic moduli of cubic subvolumes of trabecular bone predicted whole bone or trabecular bone stiffness in distal tibia. We conclude that microstructural measurements and mechanical parameters of distal tibia can be efficiently derived from HR‐pQCT images and provide additional information regarding bone fragility. © 2010 American Society for Bone and Mineral Research     

Assessment of trabecular bone structure comparing magnetic resonance imaging at 3 Tesla with high-resolution peripheral quantitative computed tomography ex vivo and in vivo

Summary In vivo high-resolution peripheral quantitative micro-CT (HR-pQCT) is a new modality for imaging peripheral sites like the distal tibia and the distal radius, providing structural bone parameters. Comparing HR-pQCT with MRI, we found that both modalities are capable of offering meaningful information on trabecular structure. Background Magnetic resonance imaging (MRI) has emerged as the leading in vivo method for measuring trabecular bone micro-architecture and providing structural information. Recently, an in vivo HR-pQCT modality was introduced for imaging peripheral sites like the distal tibia and the distal radius, providing structural bone parameters. The goal of this work was to compare and evaluate the performances and in vivo capabilities of HR-pQCT in comparison with MRI at 3 Tesla. Methods To this end images of 8 human specimens (5 tibiae and 3 radii) and 11 participants (6 tibia and 5 radii) were acquired with both modalities. Additionally, the radius specimens were scanned with micro-CT (μCT), which was used as a standard of reference. Structural parameters calculated from MRI were compared with results from HR-pQCT images and additionally μCT for the radii specimens. Results High correlations (r > 0.7) were found for trabecular number and trabecular spacing between the two modalities in vivo and ex vivo. 2D and 3D analysis revealed high correlations (r > 0.8) in structural bone parameters for all measurements. Using micro-CT as standard of reference both results from QCT and MRI correlated well. Conclusion Both imaging modalities were found to perform equally well regarding trabecular bone measurements.     

Are patterns of bone loss in anorexic and postmenopausal women similar? Preliminary results using high resolution peripheral computed tomography

This study intended to compare bone density and architecture in three groups of women: young women with anorexia nervosa (AN), an age-matched control group of young women, and healthy late postmenopausal women. Three-dimensional peripheral quantitative high resolution computed-tomography (HR-pQCT) at the ultradistal radius, a technology providing measures of cortical and trabecular bone density and microarchitecture, was performed in the three cohorts. Thirty-six women with AN aged 18–30 years (mean duration of AN: 5.8 years), 83 healthy late postmenopausal women aged 70–81 as well as 30 age-matched healthy young women were assessed. The overall cortical and trabecular bone density (D100), the absolute thickness of the cortical bone (CTh), and the absolute number of trabecules per area (TbN) were significantly lower in AN patients compared with healthy young women. The absolute number of trabecules per area (TbN) in AN and postmenopausal women was similar, but significantly lower than in healthy young women.The comparison between AN patients and post-menopausal women is of interest because the latter reach bone peak mass around the middle of the fertile age span whereas the former usually lose bone before reaching optimal bone density and structure. This study shows that bone mineral density and bone compacta thickness in AN are lower than those in controls but still higher than those in postmenopause. Bone compacta density in AN is similar as in controls. However, bone inner structure in AN is degraded to a similar extent as in postmenopause. This last finding is particularly troubling.     

Interpretation of whole body dual energy X-ray absorptiometry measures in children: comparison with peripheral quantitative computed tomography

The assessment of bone health in children requires strategies to minimize the confounding effects of bone size on dual energy X-ray absorptiometry (DXA) areal bone mineral density (BMD) results. Cortical bone composes 80% of the total skeletal bone mass. The objective of this study was to develop analytic strategies for the assessment of whole body DXA that describe the biomechanical characteristics of cortical bone across a wide range of body sizes using peripheral quantitative computed tomography (pQCT) measures of cortical geometry, density (mg/mm³), and strength as the gold standard. Whole body DXA (Hologic QDR 4500) and pQCT (Stratec XCT-2000) of the tibia diaphysis were completed in 150 healthy children 6–21 years of age. To assess DXA and pQCT measures relative to age, body size, and bone size, gender-specific regression models were used to establish z scores for DXA bone mineral content (BMC) for age, areal BMD for age, bone area for height, bone area for lean mass, BMC for height, BMC for lean mass, and BMC for bone area; and for pQCT, bone cross-sectional area (CSA) for tibia length and bone strength (stress-strain index, SSI) for tibia length. DXA bone area for height and BMC for height were both strongly and positively associated with pQCT CSA for length and with SSI for length (all P < 0.0001), suggesting that decreases in DXA bone area for height or DXA BMC for height represent narrower bones with less resistance to bending. DXA BMC for age (P < 0.01) and areal BMD (P < 0.05) for age were moderately correlated with strength. Neither DXA bone area for lean mass nor BMC for lean mass correlated with pQCT CSA for length or SSI for length. DXA BMC for bone area was weakly associated with pQCT SSI for length, in females only. Therefore, normalizing whole body DXA bone area for height and BMC for height provided the best measures of bone dimensions and strength. DXA BMC normalized for bone area and lean mass were poor indicators of bone strength.     

The effect of microcomputed tomography scanning and reconstruction voxel size on the accuracy of stereological measurements in human cancellous bone

Stereological parameters have been used as an approximation for the architecture of trabecular bone. Structural indices such as bone volume fraction (BV/TV), trabecular number (Tb.N), trabecular thickness (Tb.Th), trabecular separation (Tb.Sp), bone surface-to-volume ratio (BS/BV), degree of anisotropy (MIL1/MIL3), and connectivity density (−Euler/Vol) have been widely studied to investigate pathological conditions in bone. Due to its high resolution and nondestructiveness, microcomputed tomography (micro-CT) has been utilized to take precise three-dimensional (3D) images of trabecular microstructures. However, spatial limitations for applying micro-CT-based analyses to large specimens, such as whole vertebral bodies, require using larger scanning and reconstruction voxel sizes.

In this study, combinations of three different scanning and reconstruction voxel size were used to represent best possible voxel size (21 μm; best in our scanner for the specimen size used) relative to other voxel sizes used in this study, commonly used intermediate voxel sizes (50 μm), and those applicable to scans of whole human vertebral bodies (110 μm) in order to examine the effect of scanning and reconstruction voxel size on stereological measures for human cancellous bone.

The error in stereological parameters calculated using combinations of large voxel sizes compared to the gold standard (best possible case) ranged from 0.1% to 102%. The signed magnitude of the error in other cases relative to the gold standard was a function of either scanning or reconstruction voxel size or both (r² = 0.55–0.95). For most of the structural indices, the results from analysis of images with larger voxel sizes were correlated with those from the gold standard (r² = 0.55–0.99) except for Tb.N at 110/110 μm, MIL1/MIL3 at larger than 110 μm reconstruction voxel size, and −Euler/Vol at any combination of voxel sizes. Overall, it was observed that resampling a high resolution image at lower resolutions (corresponding to increasing reconstruction voxel size in this study) had different effects on the calculated parameters than scanning at the same low resolution (corresponding to increasing scanning voxel size in this study). Our results show that investigations of image resolution should include actual scans at the resolution of interest rather than simply coarsening of high-resolution images as is customarily done.