Background
The role of bone structure, one component of bone quality, has emerged as a contributor to bone strength. The application of high-resolution imaging in evaluating bone structure has ...evolved from an in vitro technology for small specimens to an emerging clinical research tool for in vivo studies in humans. However, many technical and practical challenges remain to translate these techniques into established clinical outcomes.
Questions/purposes
We reviewed use of high-resolution CT for evaluating trabecular microarchitecture and cortical ultrastructure of bone specimens ex vivo, extension of these techniques to in vivo human imaging studies, and recent studies involving application of high-resolution CT to characterize bone structure in the context of skeletal disease.
Methods
We performed the literature review using PubMed and Google Scholar. Keywords included CT, MDCT, micro-CT, high-resolution peripheral CT, bone microarchitecture, and bone quality.
Results
Specimens can be imaged by micro-CT at a resolution starting at 1 μm, but in vivo human imaging is restricted to a voxel size of 82 μm (with actual spatial resolution of ~ 130 μm) due to technical limitations and radiation dose considerations. Presently, this mode is limited to peripheral skeletal regions, such as the wrist and tibia. In contrast, multidetector CT can assess the central skeleton but incurs a higher radiation burden on the subject and provides lower resolution (200–500 μm).
Conclusions
CT currently provides quantitative measures of bone structure and may be used for estimating bone strength mathematically. The techniques may provide clinically relevant information by enhancing our understanding of fracture risk and establishing the efficacy of antifracture for osteoporosis and other bone metabolic disorders.
Abstract Quantitative cortical microarchitectural end points are important for understanding structure–function relations in the context of fracture risk and therapeutic efficacy. This technique ...study details new image-processing methods to automatically segment and directly quantify cortical density, geometry, and microarchitecture from HR-pQCT images of the distal radius and tibia. An automated segmentation technique was developed to identify the periosteal and endosteal margins of the distal radius and tibia and detect intracortical pore space morphologically consistent with Haversian canals. The reproducibility of direct quantitative cortical bone indices based on this method was assessed in a pooled data set of 56 subjects with two repeat acquisitions for each site. The in vivo precision error was characterized using root mean square coefficient of variation (RMSCV%) from which the least significant change (LSC) was calculated. Bland–Altman plots were used to characterize bias in the precision estimates. The reproducibility of cortical density and cross-sectional area measures was high (RMSCV < 1% and < 1.5%, respectively) with good agreement between young and elder medians. The LSC for cortical porosity (Ct.Po) was somewhat smaller in the radius (0.58%) compared with the distal tibia (0.84%) and significantly different between young and elder medians in the distal tibia (LSC: 0.75% vs. 0.92%, p < 0.001). The LSC for pore diameter and distribution (Po.Dm and Po.Dm.SD) ranged between 15 and 23 µm. Bland–Altman analysis revealed moderate bias for integral measures of area and volume but not for density or microarchitecture. This study indicates that HR-pQCT measures of cortical bone density and architecture can be measured in vivo with high reproducibility and limited bias across a biologically relevant range of values. The results of this study provide informative data for the design of future clinical studies of bone quality.
High-resolution peripheral quantitative computed tomography (HR-pQCT), which enables in vivo analysis of bone morphometry, is widely used in osteoporosis research. The scan position is usually ...determined by the fixed offset method; however, there are concerns that the scan position can become relatively proximal if limb length is short. The present study compared bone mineral density and morphometry measured using the fixed and relative offset methods, in which the scan position is determined based on the lengths of the forearm and lower leg, and investigated factors responsible for measurement differences between the two methods.
A total of 150 healthy Japanese subjects, comprising 75 men and 75 women, with a mean age of 45.1 years, were enrolled in this study. The distal radius and tibia were scanned using the fixed and relative offset methods; the fixed offset method involved scanning the radius and tibia at 9 mm and 22 mm, respectively, proximal to their distal articular surfaces. By contrast, the relative offset method entailed scanning the radius at 4% of the forearm length and the tibia at 7.3% of the lower leg length, proximal to their respective distal articular surfaces. The percent overlap between the scan positions of the two methods was measured using the scout views. Measurement values obtained with the two methods were compared. The correlation between the differences in the values among the two methods and forearm length, lower leg length, and body height was examined.
The subjects had a mean height of 164.3 ± 14.3 cm, mean forearm length of 252.9 ± 17.3 mm, and mean lower leg length of 346.7 ± 22.3 mm. The mean percent overlap was 85.0 ± 9.1% (59.2–99.6%) for the radius and 79.8 ± 12.5% (48.3–99.8%) for the tibia. Fixed offset scanning yielded higher total volumetric bone mineral density (Tt.vBMD) and cortical vBMD (Ct.vBMD) and greater cortical thickness (Ct.Th) (all p < 0.001). The differences between the two methods in terms of Tt.vBMD, Ct.vBMD and Ct.Th were significantly greater with shorter forearm length, lower leg length, and body height (radius: 0.51 < |r| < 0.63, tibia: 0.61 < |r| < 0.95).
Measurements of bone mineral density and morphometry obtained using the fixed offset method differed from those obtained using the relative offset method, which takes body size into account. Shorter body height, forearm length, and lower leg length were found to correlate with greater measurement differences. In populations with smaller stature, use of the fixed offset method results in relatively proximal images; thus, caution should be exercised when comparing groups of different height.
•We compared the fixed offset and relative offset methods of HR-pQCT.•Shorter body height was correlated with greater measurement differences.•Caution should be exercised when comparing groups of different height.
Context: Cross-sectional epidemiological studies have found that patients with type 2 diabetes mellitus (T2DM) have a higher incidence of certain fragility fractures despite normal or elevated bone ...mineral density (BMD).
Objective: In this study, high-resolution peripheral quantitative computed tomography was applied to characterize cortical and trabecular microarchitecture and biomechanics in the peripheral skeleton of female patients with T2DM.
Design and Setting: A cross-sectional study was conducted in patients with T2DM recruited from a diabetic outpatient clinic.
Participants: Elderly female patients (age, 62.9 ± 7.7 yr) with a history of T2DM (n = 19) and age- and height-matched controls (n = 19) were recruited.
Outcome Measures: Subjects were imaged using high-resolution peripheral quantitative computed tomography at the distal radius and tibia. Quantitative measures of volumetric (BMD), cross-sectional geometry, trabecular and cortical microarchitecture were calculated. Additionally, compressive mechanical properties were determined by micro-finite element analysis.
Results: Compared to the controls, the T2DM cohort had 10% higher trabecular volumetric BMD (P < 0.05) adjacent to the cortex and higher trabecular thickness in the tibia (13.8%; P < 0.05). Cortical porosity differences alone were consistent with impaired bone strength and were significant in the radius (>+50%; P < 0.05), whereas pore volume approached significance in the tibia (+118%; P = 0.1).
Conclusion: The results of this pilot investigation provide a potential explanation for the inability of standard BMD measures to explain the elevated fracture incidence in patients with T2DM. The findings suggest that T2DM may be associated with impaired resistance to bending loads due to inefficient redistribution of bone mass, characterized by loss of intracortical bone offset by an elevation in trabecular bone density.
This cross-sectional high resolution peripheral QCT study indicates that postmenopausal women with type 2 diabetes have cortical and trabecular architectural abnormalities compared to matched controls.
Purpose:
Accurate quantification of bone microstructure plays a significant role in understanding bone mechanics and response to disease or treatment. High-resolution peripheral quantitative computed ...tomography (HR-pQCT) allows for the quantification of trabecular and cortical structurein vivo, with the capability of generating images at multiple voxel sizes (41, 82, and 123 μm). The aim of this study was to characterize the effect of voxel size on structural measures of trabecular and cortical bone and to determine accuracy in reference to micro-CT (µCT), the gold standard for bone microstructure quantification.
Methods:
Seventeen radii from human cadaver specimens were imaged at each HR-pQCT voxel size and subsequently imaged using µCT. Bone density and microstructural assessment was performed in both the trabecular and cortical compartments, including cortical porosity quantification. Two distinct analysis techniques were applied to the 41 μm HR-pQCT data: the standard clinical indirect analysis and a direct analysis requiring no density or structural model assumptions. Analysis parameters were adjusted to enable segmentation and structure extraction at each voxel size.
Results:
For trabecular microstructural measures, the 41 μm HR-pQCT data displayed the strongest correlations and smallest errors compared to µCT data. The direct analysis technique applied to the 41 μm data yielded an additional improvement in accuracy, especially for measures of trabecular thickness. The 123 μm data performed poorly, with all microstructural measures either having moderate or nonsignificant correlations with µCT data. Trabecular densitometric measures showed strong correlations to µCT data across all voxel sizes. Cortical thickness was strongly correlated with µCT values across all HR-pQCT voxel sizes. The accuracy of cortical porosity parameters was highly dependent on voxel size; again, the 41 μm data was most strongly correlated. Measures of cortical density and pore diameter at all HR-pQCT voxel sizes had either weak or nonsignificant correlations.
Conclusions:
This study demonstrates the effect of voxel size on the accuracy of HR-pQCT measurements of trabecular and cortical microstructure and presents parameters for HR-pQCT analysis at nonstandard resolutions. For all parameters measured, correlations were strongest at 41 μm. Weak correlations for porosity measures indicate that a better understanding of pore structure and resolution dependence is needed.
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