Introduction

Trabecular bone in the femoral head has a complicated and heterogeneous structure with few studies having analyzed heterogeneity in this structure quantitatively. We analyze trabecular bone microstructure in the femoral head with osteoporosis (OP) using high resolution peripheral quantitative CT (HR-pQCT) to investigate its regional characteristics.

Methods

Fifteen femoral heads extracted from female OP patients with femoral neck fracture (85 ± 7, 67-94 years) were scanned by HR-pQCT at 41 μm voxel size. The femoral head was segmented into 15 regions (3 longitudinal regions: superior, center, and inferior, and 5 axial subregions: center, medial, lateral, anterior, posterior). Of these 15 regions, five were excluded due to overlap with the fracture site, leaving a total of 10 regions of cancellous bone microstructures to be quantitatively assessed using the following parameters: bone volume fraction, trabecular thickness, number, separation, connectivity density, structure model index, and degree and orientation of anisotropy. These parameters were compared among each region.

Results

Trabecular bone at the center, superior, and supero-posterior regions of the femoral head had higher bone volume, trabecular number, thickness, narrower bone marrow spaces, higher connectivity and anisotropy, and more plate-like structure. This plate-like structure ran supero-inferiorly and antero-posteriorly at the superior and center regions. Bone volume at the anterior, posterior, and medial regions was almost half of the central and superior regions.

Conclusion

Significant heterogeneity of the trabecular bone microstructure in the OP femoral head was showed quantitatively in this study. These data offer new insight into bone microstructural anatomy and may prove to provide useful information on clinical medicine such as hip surgeries.

Introduction

Subchondral cysts are deeply related to the pathogenesis of osteoarthritis (OA), but the factors contributing to cyst formation are not well known. A three-dimensional analysis of subchondral cysts at the micro-structural level was conducted using a high-resolution peripheral quantitative CT (HR-pQCT), and their relationships with cartilage attrition and subchondral bone microstructure were investigated.

Methods

Femoral heads extracted from ten female patients with hip OA were scanned using an HR-pQCT at a voxel size of 41μm. The volume fractions, numbers, and sizes of the cysts were measured in the subchondral bone region under the area of cartilage loss. Furthermore, the areas of cartilage loss, as well as the microstructure of the subchondral bones, were also measured, and their correlations with the cysts were analyzed.

Results

The volume fractions of cysts within subchondral bone regions varied from 2% to 33%, the numbers of cysts varied from 6 to 87, and the sizes varied from 1mm(3) to 657mm(3). There was a positive correlation between the number of cysts and bone volume (r>0.8, p<0.01).

Conclusion

The degree of cyst formation showed a wide distribution in number and volume, and there was a close relationship between multiple cyst formation and bone sclerosis, which might be caused by reactive bone formation that occurred around each cyst.

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.

Purpose

The primary objective of this study was to analyze the relationships between bone microstructure and strength, and male osteoporosis risk factors including age, body mass index, serum 25-hydroxyvitamin D level, and testosterone level. A secondary objective was to compare microstructural and strength parameters between men with normal, low, and osteoporosis-range areal bone mineral density (aBMD).

Methods

Seventy-eight healthy male volunteers (mean age 62.4 ± 7.8 years, range 50-84 years) were recruited. The participants underwent dual-energy X-ray absorptiometry (DXA) and high-resolution peripheral quantitative computed tomography (HR-pQCT) of the ultra-distal radius and tibia. From the HR-pQCT images, volumetric bone mineral density (BMD) and cortical and trabecular bone microstructure were evaluated, and bone strength and cortical load fraction (Ct.LF) were estimated using micro-finite element analysis (μFEA).

Results

Age was more strongly correlated with bone microstructure than other risk factors. Age had significant positive correlations with cortical porosity at both ultra-distal radius and tibia (r = 0.36, p = 0.001, and r = 0.47, p < 0.001, respectively). At the tibia, age was negatively correlated with cortical BMD, whereas it was positively correlated with trabecular BMD. In μFEA, age was negatively correlated with Ct.LF, although not with bone strength. Compared with men with normal aBMD, men with low or osteoporosis-range aBMD had significantly poor trabecular bone microstructure and lower bone strength at the both sites, while there was no significant difference in cortical bone.

Conclusions

Cortical bone microstructure was negatively affected by aging, and there was a suggestion that the influence of aging may be particularly important at the weight-bearing sites.

Objective

While the importance of cortical structure quantification is increasingly underscored by recent literature, conventional analysis techniques obscure potentially important regional variations in cortical structure. The objective of this study was to characterize the spatial variability in cortical geometry and microstructure at the distal radius and tibia using high resolution peripheral quantitative computed tomography (HR-pQCT). We show that spatially-resolved analysis is able to identify cortical sub-regions with increased sensitivity to the effects of gender and aging.

Methods

HR-pQCT scans of 146 volunteers (92 female/54 male) spanning a wide range of ages (20-78years) were analyzed. For each subject, radius and tibia scans were obtained using a clinical HR-pQCT system. Measures describing geometry (cortical bone thickness (Ct.Th)), microstructure (porosity (Ct.Po), pore diameter (Ct.Po.Dm), and pore size heterogeneity (Ct.Po.Dm SD)), and cortical bone density were calculated from the image data. Biomechanical parameters describing load and stress distribution were calculated using linear finite element analysis. Cortical quadrants were defined based on anatomic axes to quantify regional parameter variation. Subjects were categorized by gender, and age, and menopausal status for analysis.

Results

Significant regional variation was found in all geometric and microstructural parameters in both the radius and tibia. In general, the radius showed more pronounced and significant variations in all parameters as compared with the tibia. At both sites, Ct.Po displayed the greatest regional variations. Correlation coefficients for Ct.Po and Ct.Th with respect to load and stress distribution provided evidence of an association between regional cortical structure and biomechanics in the tibia. Comparing women to men, differences in Ct.Po were most pronounced in the anterior quadrant of the radius (36% lower in women (p<0.01)) and the posterior quadrant of the tibia (27% lower in women (p<0.01)). Comparing elderly to young women, differences in Ct.Po were most pronounced in the lateral quadrant of the radius (328% higher in elderly women (p<0.001)) and the anterior quadrant of the tibia (433% higher in elderly women (p<0.001)). Comparing elderly to young men, the most pronounced age differences were found in the anterior radius (205% higher in elderly men, (p<0.001)) and the anterior tibia (190% higher in elderly men (p<0.01)). All subregional Ct.Po differences provided greater sensitivity to gender and age effects than those based on the global means.

Conclusion

These results show significant regional variation in all geometric and microarchitectural parameters studied in both the radius and tibia. Quantification of region-specific parameters provided increased sensitivity in the analysis of age- and gender-related differences, in many cases providing statistically significant differentiation of groups where conventional global analysis failed to detect differences. These results suggest that regional analysis may be important in studies of disease and therapeutic effects, particularly where microstructural parameters based on global analyses have thus far failed to identify a response in bone quality.

Background

Bone parameters derived from HR-pQCT have been investigated on a parameter-by-parameter basis for different clinical conditions. However, little is known regarding the interrelationships of bone parameters and the spatial distribution of these interrelationships. In this work: 1) we investigate compartmental interrelationships of bone parameters; 2) assess the spatial distribution of interrelationships of bone parameters; and 3) compare interrelationships of bone parameters between postmenopausal women with and without a recent Colles' fracture.

Methods

Images from the unaffected radius in fracture cases (n=84), and from the non-dominant radius of controls (n=98) were obtained using HR-pQCT. Trabecular voxel-based maps of local bone volume fraction (L.Tb.BV/TV), homogenized volumetric bone mineral density (H.Tb.BMD), homogenized μFEA-derived strain energy density (H.Tb.SED), and homogenized inter-trabecular distances (H.Tb.1/N) were generated; as well as surface-based maps of apparent cortical bone thickness (Surf.app.Ct.Th), porosity-weighted cortical bone thickness (Surf.Ct.SIT), mean cortical BMD (Surf.Ct.BMD), and mean cortical SED (Surf.Ct.SED). Anatomical correspondences across the parametric maps in the study were established via spatial normalization to a common template. Mean values of the parametric maps before spatial normalization were used to assess compartmental Spearman's rank partial correlations of bone parameters (e.g., between H.Tb.BMD and L.Tb.BV/TV or between Surf.Ct.BMD and Surf.app.Ct.Th). Spearman's rank partial correlations were also assessed for each voxel and vertex of the spatially normalized parametric maps, thus generating maps of Spearman's rank partial correlation coefficients. Correlations were performed independently within each group, and compared between groups using the Fisher's Z transformation.

Results

All within-group global trabecular and cortical Spearman's rank partial correlations were significant; and the correlations of H.Tb.BMD-L.Tb.BV/TV, H.Tb.BMD-H.Tb.1/N, L.Tb.BV/TV-H.Tb.1/N, Surf.Ct.BMD-Surf.Ct.SED and Surf.Ct.SIT-Surf.Ct.SED were significantly different between controls and fracture cases. The spatial analyses revealed significant heterogeneous voxel- and surface-based correlation coefficient maps across the distal radius for both groups; and the correlation maps of H.Tb.BMD-L.Tb.BV/TV, H.Tb.BMD-H.Tb.1/N, L.Tb.BV/TV-H.Tb.1/N, H.Tb.1/N-H.Tb.SED and Surf.app.Ct.Th - Surf.Ct.SIT yielded small clusters of significant correlation differences between groups.

Discussion

The heterogeneous spatial distribution of interrelationships of bone parameters assessing density, microstructure, geometry and biomechanics, along with their global and local differences between controls and fracture cases, may help us further understand different bone mechanisms of bone fracture.

Purpose

The investigation of cortical porosity is an important aspect of understanding biological, pathoetiological, and biomechanical processes occurring within the skeleton. With the emergence of HR-pQCT as a noninvasive tool suitable for clinical use, cortical porosity at appendicular sites can be directly visualized in vivo. The aim of this study was to introduce a novel topological analysis of the cortical pore network for HR-pQCT data and determine the influence of resolution on measures of cortical pore network microstructure and topology.

Methods

Cadaveric radii were scanned using HR-pQCT at two different voxel sizes (41 and 82 μm) and also using μCT at a voxel size of 18 μm. HR-pQCT and μCT image sets were spatially coregistered. Segmentation and quantification of cortical porosity (Ct.Po) and mean pore diameter (Ct.Po.Dm) were achieved using an established extended cortical analysis technique. Topological classification of individual pores was performed using topology-preserving skeletonization and multicolor dilation algorithms. Based on the pore skeleton topological classification, the following parameters were quantified: total number of planar surface-skeleton canals (N.Slabs), tubular curve-skeleton canals (N.Tubes), and junction elements (N.Junctions), mean slab volume (Slab.Vol), mean tube volume (Tube.Vol), mean slab orientation (Slab.θ), mean tube orientation (Tube.θ), N.Slabs/N.Tubes, and integral (total) slab volume/integral tube volume (iSlab.Vol/iTube.Vol). An in vivo reproducibility study was also conducted to assess short-term precision of the topology parameters. Precision error was characterized using root mean square coefficient of variation (RMSCV%).

Results

Correlations to μCT values for Ct.Po were significant for both the 41 and 82 μm HR-pQCT data (41: r(2) = 0.82, p < 0.001, 82: r(2) = 0.75, p < 0.001). For Ct.Po.Dm, only the 41 μm data were significantly predictive of μCT values (r(2) = 0.72, p < 0.01) Data at both HR-pQCT voxel sizes were strongly predictive of the μCT values for N.Slabs (41: r(2) = 0.93, p < 0.001; 82: r(2) = 0.84, p < 0.001), N.Tubes (41: r(2) = 0.94, p < 0.001; 82: r(2) = 0.84, p < 0.001), and N.Junctions (41: r(2) = 0.93, p < 0.001; 82: r(2) = 0.78, p < 0.001), though proportional bias was evident in these correlations. Weak correlations were seen for iSlab.Vol/iTube.Vol at both voxel sizes (41: r(2) = 0.52, p < 0.01; 82: r(2) = 0.39, p < 0.05). Slab.Vol was significantly correlated to μCT data at 41 μm (r(2) = 0.60, p < 0.01) but not at 82 μm, while Tube.Vol was significantly correlated at both voxel sizes (41: r(2) = 0.79, p < 0.001; 82: r(2) = 0.68, p < 0.01). In vivo precision error for these parameters ranged from 2.31 to 9.68 RMSCV%.

Conclusions

Strong correlations between μCT- and HR-pQCT-derived measurements were found, particularly in HR-pQCT images obtained at 41 μm. These data are in agreement with our previous study investigating the effect of voxel size on standard HR-pQCT metrics of trabecular and cortical microstructure, and extend our previous findings to include topological descriptors of the cortical pore network.

Cortical bone contributes the majority of overall bone mass and bears the bulk of axial loads in the peripheral skeleton. Bone metabolic disorders often are manifested by cortical microstructural changes via osteonal remodeling and endocortical trabecularization. The goal of this study was to characterize intracortical porosity in a cross-sectional patient cohort using novel quantitative computational methods applied to high-resolution peripheral quantitative computed tomography (HR-pQCT) images of the distal radius and tibia. The distal radius and tibia of 151 subjects (57 male, 94 female; 47 +/- 16 years of age, range 20 to 78 years) were imaged using HR-pQCT. Intracortical porosity (Ct.Po) was calculated as the pore volume normalized by the sum of the pore and cortical bone volume. Micro-finite element analysis (microFE) was used to simulate 1% uniaxial compression for two scenarios per data set: (1) the original structure and (2) the structure with intracortical porosity artificially occluded. Differential biomechanical indices for stiffness (Delta K), modulus (Delta E), failure load (Delta F), and cortical load fraction (Delta Ct.LF) were calculated as the difference between original and occluded values. Regression analysis revealed that cortical porosity, as depicted by HR-pQCT, exhibited moderate but significant age-related dependence for both male and female cohorts (radius rho = 0.7; tibia rho = 0.5; p < .001). In contrast, standard cortical metrics (Ct.Th, Ct.Ar, and Ct.vBMD) were more weakly correlated or not significantly correlated with age in this population. Furthermore, differential microFE analysis revealed that the biomechanical deficit (Delta K) associated with cortical porosity was significantly higher for postmenopausal women than for premenopausal women (p < .001). Finally, porosity-related measures provided the only significant decade-wise discrimination in the radius for females in their fifties versus females in their sixties (p < .01). Several important conclusions can be drawn from these results. Age-related differences in cortical porosity, as detected by HR-pQCT, are more pronounced than differences in standard cortical metrics. The biomechanical significance of these structural differences increases with age for men and women and provides discriminatory information for menopause-related bone quality effects.

High-resolution peripheral quantitative computed tomography (HR-pQCT) has emerged as a powerful imaging technique for characterizing bone microarchitecture in the human peripheral skeleton. The second-generation HR-pQCT scanner provides improved spatial resolution and a shorter scan time. However, the transition from the first-generation (XCTI) to second-generation HR-pQCT scanners (XCTII) poses challenges for longitudinal studies, multi-center trials, and comparison to historical data. Cross-calibration, an established approach for determining relationships between measurements obtained from different devices, can bridge this gap and enable the utilization and comparison of legacy data. The goal of this study was to establish cross-calibration equations to estimate XCTII measurements from XCTI data, using both the standard and Laplace-Hamming (LH) binarization approaches. Thirty-six volunteers (26-85 yr) were recruited and their radii and tibiae were scanned on both XCTI and XCTII scanners. XCTI images were analyzed using the manufacturer's standard protocol. XCTII images were analyzed twice: using the manufacturer's standard protocol and the LH segmentation approach previously developed and validated by our team. Linear regression analysis was used to establish cross-calibration equations. Results demonstrated strong correlations between XCTI and XCTII density and geometry outcomes. For most microstructural outcomes, although there were considerable differences in absolute values, correlations between measurements obtained from different scanners were strong, allowing for accurate cross-calibration estimations. For some microstructural outcomes with a higher sensitivity to spatial resolution (eg, trabecular thickness, cortical pore diameter), XCTII standard protocol resulted in poor correlations between the scanners, while our LH approach improved these correlations and decreased the difference in absolute values and the proportional bias for other measurements. For these reasons and due to the improved accuracy of our LH approach compared with the standard approach, as established in our previous study, we propose that investigators should use the LH approach for analyzing XCTII scans, particularly when comparing to XCTI data.

Osteoarthritis (OA) is a major degenerative joint disease characterized by progressive loss of articular cartilage, synovitis, subchondral bone changes, and osteophyte formation. Currently there is no treatment for OA except temporary pain relief and end-stage joint replacement surgery. We performed a pilot study to determine the effect of kartogenin (KGN, a small molecule) on both cartilage and subchondral bone in a rat model of OA using multimodal imaging techniques. OA was induced in rats (OA and KGN treatment group) by anterior cruciate ligament transection (ACLT) surgery in the right knee joint. Sham surgery was performed on the right knee joint of control group rats. KGN group rats received weekly intra-articular injection of 125 μM KGN 1 week after surgery until week 12. All rats underwent in vivo magnetic resonance imaging (MRI) at 3, 6, and 12 weeks after surgery. Quantitative MR relaxation measures (T_1ρ and T₂ ) were determined to evaluate changes in articular cartilage. Cartilage and bone turnover markers (COMP and CTX-I) were determined at baseline, 3, 6, and 12 weeks. Animals were sacrificed at week 12 and the knee joints were removed for micro-computed tomography (micro-CT) and histology. KGN treatment significantly lowered the T_1ρ and T₂ relaxation times indicating decreased cartilage degradation. KGN treatment significantly decreased COMP and CTX-I levels indicating decreased cartilage and bone turnover rate. KGN treatment also prevented subchondral bone changes in the ACLT rat model of OA. Thus, kartogenin is a potential drug to prevent joint deterioration in post-traumatic OA. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1780-1789, 2016.