Contribution of high resolution peripheral quantitative CT to the management of bone and joint diseases

Many imaging modalities have been described to diagnose and monitor osteoporosis (OP), osteoarthritis and inflammatory rheumatic diseases. Over the last ten years, High Resolution peripheral Quantitative Computerized Tomography (HR-pQCT) was shown to be a precise and non invasive technique to study bone and joint diseases in clinical research. It allows the study of both cortical and trabecular bone microarchitecture at the distal tibia and radius, and further applications have been developed such as the study of mechanical properties by the finite element analysis. Thus, in case-control and cross-sectional studies, microarchitecture parameters discriminated fractured individuals independently of areal BMD. Also, microstructure parameters can predict incident fracture in postmenopausal women. In metabolic diseases associated with bone fragility, HR-pQCT may also be used to explore bone changes. In joint disease studies, HR-pQCT was a remarkable tool to assess bone erosion and joint space narrowing at the hand. This article gives an overview of this imaging technique.     

Underdeveloped trabecular bone microarchitecture is detected in children with cerebral palsy using high-resolution magnetic resonance imaging

Summary Using high resolution magnetic resonance imaging, we detected severely underdeveloped trabecular bone microarchitecture in the distal femur of children with cerebral palsy who can not ambulate independently vs. typically developing controls. Furthermore, very good short-term reliability of trabecular bone microarchitecture measurements was observed in both groups of children. Introduction Severe forms of cerebral palsy (CP) are associated with very low areal bone mineral density and a very high incidence of fracture in the distal femur; however, the state of trabecular bone microarchitecture has not been evaluated. Furthermore, the short-term reliability of trabecular bone microarchitecture assessment in children using high-resolution magnetic resonance imaging (MRI) has not been determined. Methods Apparent bone volume to total volume (appBV/TV), trabecular number, (appTb.N), trabecular thickness (appTb.Th) and trabecular separation (appTb.Sp) were determined in the distal femur of non-ambulatory children with CP and typically developing children using MRI. Results Children with CP had a 30% lower appBV/TV, a 21% lower appTb.N, a 12% lower appTb.Th and a 48% higher appTb.Sp in the distal femur than controls (n = 10/group; P < 0.001). The short-term reliability of the trabecular bone microarchitecture measures was very good, with coefficients of variation ranging from 2.0 to 3.0% in children with CP (n = 6) and 1.8 to 3.5% in control children (n = 6). Conclusions Underdeveloped trabecular bone microarchitecture can be detected in the distal femur of children with CP who can not ambulate independently using high-resolution MRI. Furthermore, MRI can be used to assess trabecular bone microarchitecture in children with a high degree of reliability. Grant Support: United Cerebral Palsy Research and Educational Foundation and the University of Delaware Research Foundation.     

Imaging techniques for evaluating bone microarchitecture

At present, fracture risk prediction in the individual patient relies chiefly on bone mineral density (BMD) measurements. However, many lines of evidence indicate that the decreased bone strength characteristic of osteoporosis is dependent not only on BMD, but also on other factors, most notably bone microarchitecture. Here, we review available tools for characterizing trabecular microarchitecture (in terms of morphology, topology, and texture) and for obtaining 2D and 3D images (using radiography, computed tomography, and magnetic resonance imaging). Bone microarchitecture imaging is a noninvasive method that may improve fracture risk prediction in the individual patient, shed light on the pathophysiology of osteoporosis, and help to monitor the effects of treatments. Among the various methods available to date, magnetic resonance imaging has the advantage of involving no radiation exposure, although its limited availability restricts its usefulness for studying vast populations. Regardless of the methods selected to assess bone microarchitecture, there is a need for validated standardized parameters capable of improving fracture risk prediction in longitudinal studies.     

Trabecular bone failure at the microstructural level

Although biomedical imaging technology is now readily available, few attempts have been made to expand the capabilities of these systems by adding not only quantitative but also functional analysis tools combining microimaging with time-lapsed mechanical testing. An area of special interest is multiscale functional imaging of trabecular bone to assess the relative importance of bone “quality” in the assessment of the mechanical competence of bone. First, relevant studies dealing with hierarchical imaging of trabecular bone and classic analyses such as quantitative morphometry and finiteelement analysis to predict bone strength are reviewed. Second, studies are presented investigating failure mechanisms of three-dimensional trabecular bone through dynamic, time-lapsed microimaging, including image-guided techniques developed for this purpose and utilizing microcompression. For the first time, these allow the direct three-dimensional visualization and quantification of failure initiation and progression at the microstructural level.     

TBS在监测及诊断骨质疏松方面的应用价值

利用DXA（dual energy X-ray absorptiometry,双能X线吸收法）测得的单位面积骨密度值（areal bone mineral density,BMD）是诊断骨质疏松的金标准。骨质疏松患者骨量减少的同时通常存在骨微结构的退化,表现为骨小梁数量减少、间距增加以及骨小梁间连接性下降,而BMD仅能显示骨量的变化,不能提供关于骨结构的信息。因此,仅靠BMD来诊断或排除骨质疏松是不全面的。骨小梁分数（trabecular bone score,TBS）是一种可由DXA图像获得的反映图像上灰阶变化的结构参数,能有效评估骨的微结构、描述骨的质量。本文将从TBS的检测方法、与其他检测骨折风险指标之间的关系以及TBS的有效性和不足等方面来介绍TBS在监测及诊断骨质疏松方面的应用价值。     

Effects of salmon calcitonin on trabecular microarchitecture as determined by magnetic resonance imaging: results from the QUEST study.

The unique noninvasive MRI technique was used to assess trabecular microarchitecture at multiple skeletal sites in 91 postmenopausal osteoporotic women receiving nasal spray salmon calcitonin (CT-NS) or placebo over 2 years. In the distal radius and lower trochanter of the hip, individuals treated with CT-NS exhibited significant preservation of trabecular bone microarchitecture compared with placebo, where significant deterioration was shown. MRI analyses of os calcis or microCT/histomorphometric analyses of bone biopsies did not reveal consistent differences in architecture between CT-NS and placebo. INTRODUCTION: It is postulated that the reduction in osteoporotic fracture risk in response to certain antiresorptive osteoporosis therapies is caused less by effects on bone quantity than on bone quality (specifically trabecular microarchitecture). To test this hypothesis, the QUEST study was conducted to assess the effects of nasal spray salmon calcitonin (CT-NS) or placebo on parameters of trabecular microarchitecture at multiple skeletal sites using noninvasive MRI technology and iliac crest bone biopsies by microCT/histomorphometry. MATERIALS AND METHODS: Ninety-one postmenopausal osteoporotic women were followed for 2 years (n = 46 for CT-NS, n = 45 for placebo); all women received 500 mg calcium daily. MRI measurements at distal radius, hip (T2 relaxation time [T2*]), and os calcis (obtained yearly), iliac crest bone biopsies with 2D histomorphometry and 3D microCT (obtained at study onset and conclusion), DXA-BMD at spine/hip/wrist/os calcis (obtained yearly), and markers of bone turnover (obtained at 2-week to 12-month intervals) were analyzed, with an analysis of covariance model used to assess treatment effect for parameters of interest. RESULTS AND CONCLUSIONS: MRI assessment of trabecular microarchitecture at individual regions of the distal radius revealed significant improvement, or preservation (no significant loss), in the CT-NS-treated group compared with significant deterioration in the placebo control group, as reflected in apparent BV/TV (p < 0.03), apparent trabecular number (p < 0.01), and apparent trabecular spacing (p < 0.01). Also, at the hip, the CT-NS group exhibited preservation of trabecular microarchitecture at the lower trochanter (p < 0.05) as determined by T2* MRI technology. Significant deterioration of trabecular bone architecture was noted in the placebo group at the femoral neck, Ward's triangle, and lower trochanteric sites. Apart from a significant increase in apparent trabecular number in the CT-NS group, significant changes within or between groups were not noted at the os calcis. Combined microCT/histomorphometric analysis of iliac crest bone biopsies did not reveal significant differences between treated and placebo groups. In the CT-NS group, regardless of the change in BMD (gain or loss) at the spine, hip, or distal radius, preservation of parameters of trabecular microarchitecture was noted, whereas in the placebo group, regardless of the change in BMD (gain or loss) at the spine, hip, or distal radius, loss or preservation was noted; however, changes in DXA/BMD (of the spine, hip, wrist, os calcis) between CT-NS and placebo groups were not significant. Serum C-telopeptide (S-CTx), a specific bone resorption marker, was reduced by 22.5% at 24 months (p = 0.056). The results of the QUEST study suggest therapeutic benefit of CT-NS compared with placebo in maintaining trabecular microarchitecture at multiple skeletal sites and support the use of MRI technology for assessment of trabecular microarchitecture in clinical research trials. However, the results also highlight site specific differences in response to antiresorptive therapies and the importance of sufficiently large sampling volumes (areas) to obtain reliable assessment of bone architecture.     

Microarchitecture et résistance mécanique osseuse

Although bone mass is the main determinant of bone mechanical resistance, it explains only 30% to 40% of the variability of this characteristic, indicating that other factors are involved. Among these factors is bone tissue quality, which depends on bone mineralization, bone turnover, and bone microarchitecture. Several parameters for characterizing bone microarchitecture have been developed over the last 15 years. The simplest (Parfitt’s parameters) are trabecular count, width, and separation. A binary image (two levels of gray) of bone tissue can be expanded and used to determine the trabecular bone pattern factor. This method tends to overestimate the number of convex surfaces, which are characteristic of trabecular network disruption. The binary image can be further simplified (skeletonized) and used to count the number of nodes (anastomoses between trabeculae) or free ends (segments disconnected from the network). The bone marrow star volume, the marrow interconnectivity index, and the Euler-Poincaré number are useful for characterizing the bone marrow. These parameters can be measured on bone specimens or on computed tomography (CT) or magnetic resonance imaging (MRI) scans, although in-plane resolution is far lower with scans than with specimens. Two-dimensional analysis is widely used, although three-dimensional studies are more satisfactory. Finally, fractal analysis is an original approach in which fractal dimension measurement, which is fairly simple, is used to determine the degree of network disruption. Ex vivo histomorphometric data suggest that microarchitecture-related factors may explain 10% to 30% of the variability in bone mechanical resistance beyond the proportion explained by bone mass. Similar results have been obtained in microimaging, CT, and MRI studies. Discrepancies across studies exist, however, in the strength of the relationship between bone mass and bone mechanical resistance; they are probably ascribable to differences in measurement sites and to errors in the measurement of variables characterizing bone mechanical resistance. The finite element method may be a means of sidestepping these problems. It can be used, in particular, to calculate Young’s modulus of elasticity from three-dimensional bone segment reconstructions. The results of the few studies of the finite element method are promising but require confirmation. Finally, a more clinical approach consists in comparing bone architecture in patients with osteoporotic fractures and in controls matched on bone mass. A few cross-sectional studies have used this approach. Bone architecture was evaluated using histomorphometry, CT, or MRI. The results indicate that trabecular network disruption is more severe in patients with than without fractures.     

Assessment of proximal femur microarchitecture using ultra-high field MRI at 7 Tesla

PurposeThe purpose of this study was to investigate bone microarchitecture of cadaveric proximal femurs using ultra-high field (UHF) 7-Tesla magnetic resonance imaging (MRI) and to compare the corresponding metrics with failure load assessed during mechanical compression test and areal bone mineral density (ABMD) measured using dual-energy X-ray absorptiometry.Materials and methodsABMD of ten proximal femurs from five cadavers (5 women; mean age = 86.2 ± 3.8 (SD) years; range: 82.5–90 years) were investigated using dual-energy X-ray absorptiometry and the bone volume fraction, trabecular thickness, trabecular spacing, fractal dimension, Euler characteristics, connectivity density and degree of anisotropy of each femur was quantified using UHF MRI. The whole set of specimens underwent mechanical compression tests to failure. The inter-rater reliability of microarchitecture characterization was assessed with the intraclass correlation coefficient (ICC). Associations were searched using correlation tests and multiple regression analysis.ResultsThe inter-rater reliability for bone microarchitecture parameters measurement was good with ICC ranging from 0.80 and 0.91. ABMD and the whole set of microarchitecture metrics but connectivity density significantly correlated with failure load. Microarchitecture metrics correlated to each other but did not correlate with ABMD. Multiple regression analysis disclosed that the combination of microarchitecture metrics and ABMD improved the association with failure load.ConclusionFemur bone microarchitecture metrics quantified using UHF MRI significantly correlated with biomechanical parameters. The multimodal assessment of ABMD and trabecular bone microarchitecture using UHF MRI provides more information about fracture risk of femoral bone and might be of interest for future investigations of patients with undetected osteoporosis.     

Correlations Between Trabecular Bone Score, Measured Using Anteroposterior Dual-Energy X-Ray Absorptiometry Acquisition, and 3-Dimensional Parameters of Bone Microarchitecture: An Experimental Study on Human Cadaver Vertebrae

Developing a novel technique for the efficient, noninvasive clinical evaluation of bone microarchitecture remains both crucial and challenging. The trabecular bone score (TBS) is a new gray-level texture measurement that is applicable to dual-energy X-ray absorptiometry (DXA) images. Significant correlations between TBS and standard 3-dimensional (3D) parameters of bone microarchitecture have been obtained using a numerical simulation approach. The main objective of this study was to empirically evaluate such correlations in anteroposterior spine DXA images. Thirty dried human cadaver vertebrae were evaluated. Micro-computed tomography acquisitions of the bone pieces were obtained at an isotropic resolution of 93 μm. Standard parameters of bone microarchitecture were evaluated in a defined region within the vertebral body, excluding cortical bone. The bone pieces were measured on a Prodigy DXA system (GE Medical-Lunar, Madison, WI), using a custom-made positioning device and experimental setup. Significant correlations were detected between TBS and 3D parameters of bone microarchitecture, mostly independent of any correlation between TBS and bone mineral density (BMD). The greatest correlation was between TBS and connectivity density, with TBS explaining roughly 67.2% of the variance. Based on multivariate linear regression modeling, we have established a model to allow for the interpretation of the relationship between TBS and 3D bone microarchitecture parameters. This model indicates that TBS adds greater value and power of differentiation between samples with similar BMDs but different bone microarchitectures. It has been shown that it is possible to estimate bone microarchitecture status derived from DXA imaging using TBS.     

Trabecular bone microarchitecture is deteriorated in men with spinal cord injury.

Using magnetic resonance imaging, men with spinal cord injury (n = 10) were found to have fewer trabeculae that were spaced further apart in the knee than able-bodied controls of similar age, height, and weight (n = 8). The deteriorated trabecular bone microarchitecture may contribute to the increased fracture incidence after injury. INTRODUCTION: Spinal cord injury results in a dramatic decline in areal bone mineral density (aBMD) and a marked increase in lower extremity fracture; however, its effect on trabecular bone microarchitecture is unknown. The purpose of this study was to determine if trabecular bone microarchitecture is deteriorated in the knee of men with long-term, complete spinal cord injury. MATERIALS AND METHODS: Apparent bone volume to total volume (appBV/TV), trabecular number, (appTb.N), trabecular thickness (appTb.Th), and trabecular separation (appTb.Sp), measures of trabecular bone microarchitecture, were assessed in the distal femur and proximal tibia of men with long-term (>2 years) complete spinal cord injury (SCI; n = 10) and able-bodied controls (CON; n = 8) using high-resolution magnetic resonance imaging. Proximal tibia and arm aBMD were determined using DXA. Independent t-tests were used to assess group differences in anthropometrics and bone parameters. Pearson correlation analysis was used to assess the relationships among trabecular bone microarchitecture, aBMD, and time since injury. RESULTS: There were no group differences in age, height, or weight; however, the distal femur and proximal tibia of SCI had 27% and 20% lower appBV/TV, 21% and 20% lower appTb.N, and 44% and 33% higher appTb.Sp, respectively (p < 0.05). The distal femur of SCI also had 8% lower appTb.Th (p < 0.05). Whereas arm aBMD was not different in the two groups, proximal tibia aBMD was 43% lower in SCI. In SCI and CON combined, aBMD was correlated with appBV/TV (r = 0.62), appTb.N (r = 0.78), and appTb.Sp (r = -0.82) in the proximal tibia (p < 0.05). Time since injury was more strongly correlated with appTb.N (r = -0.54) and appTb.Sp (r = 0.56) than aBMD (r = -0.36) in the distal tibia, although none of the relationships were statistically significant (p > 0.05). CONCLUSION: Men with complete spinal cord injury have markedly deteriorated trabecular bone microarchitecture in the knee, which may contribute to their increased fracture incidence.     

Trabecular bone microarchitecture in female collegiate gymnasts

SUMMARY: Using high-resolution magnetic resonance imaging, we observed more developed trabecular bone microarchitecture in the proximal tibia of female collegiate gymnasts vs. matched controls. This suggests that high-load physical activity may have a positive effect on the trabecular microarchitecture in weight-bearing bone. INTRODUCTION: Participation in physical activities that overload the skeleton, such as artistic gymnastics, is associated with increased areal bone mineral density (aBMD); however, the status of trabecular microarchitecture in the weight-bearing bone of gymnasts is unknown. METHODS: Eight female collegiate artistic gymnasts and eight controls matched for age, height, body mass, gender and race were recruited for the study. Apparent trabecular bone volume to total volume (appBV/TV), trabecular number (appTb.N), thickness (appTb.Th) and trabecular separation (appTb.Sp) were determined using high resolution magnetic resonance imaging. Areal bone mineral density, bone mineral content (BMC) and bone area in the proximal tibia were determined using dual-energy X-ray absorptiometry. Group differences were determined using t-tests. The magnitude of group differences was expressed using Cohen's d (d). RESULTS: Gymnasts had higher appBV/TV (13.6%, d = 1.22) and appTb.N (8.4%, d = 1.45), and lower appTb.Sp (13.7%, d = 1.33) than controls (p < 0.05). Gymnasts had higher aBMD and BMC in the proximal tibia, although the differences were smaller in magnitude (d = 0.75 and 0.74, respectively) and not statistically significant (p > 0.05). CONCLUSION: The findings suggest that high-load physical activity, such as performed during gymnastics training, may enhance the trabecular microarchitecture of weight-bearing bone.     

Automated threshold-independent cortex segmentation by 3D-texture analysis of HR-pQCT scans

The quantitative assessment of metabolic bone diseases relies on tissue properties such as bone mineral density (BMD) and bone microarchitecture. In spite of an increasing number of publications using high-resolution peripheral quantitative computed-tomography (HR-pQCT), the accurate and reproducible separation of cortical and trabecular bone remains challenging. In this paper, we present a novel, fully automated, threshold-independent technique for the segmentation of cortical and trabecular bone in HR-pQCT scans. This novel post-processing method is based on modeling appearance characteristics from manually annotated cases. In our experiments the algorithm automatically selected texture features with high differentiating power and trained a classifier to separate cortical and trabecular bone. From this mask, cortical thickness and tissue volume could be calculated with high accuracy. The overlap between the proposed threshold-independent segmentation tool (TIST) and manual contouring was 0.904±0.045 (Dice coefficient). In our experiments, TIST obtained higher overall accuracy in our measurements than other techniques.     

Cross‐sectional analysis of the association between fragility fractures and bone microarchitecture in older men: The STRAMBO study

Areal bone mineral density (aBMD) measured by dual‐energy X‐ray absorptiometry (DXA) identifies 20% of men who will sustain fragility fractures. Thus we need better fracture predictors in men. We assessed the association between the low‐trauma prevalent fractures and bone microarchitecture assessed at the distal radius and tibia by high‐resolution peripheral quantitative computed tomography (HR‐pQCT) in 920 men aged 50 years of older. Ninety‐eight men had vertebral fractures identified on the vertebral fracture assessment software of the Hologic Discovery A device using the semiquantitative criteria, whereas 100 men reported low‐trauma peripheral fractures. Men with vertebral fractures had poor bone microarchitecture. However, in the men with vertebral fractures, only cortical volumetric density (D.cort) and cortical thickness (C.Th) remained significantly lower at both the radius and tibia after adjustment for aBMD of ultradistal radius and hip, respectively. Low D.cort and C.Th were associated with higher prevalence of vertebral fractures regardless of aBMD. Severe vertebral fractures also were associated with poor trabecular microarchitecture regardless of aBMD. Men with peripheral fractures had poor bone microarchitecture. However, after adjustment for aBMD, all microarchitectural parameters became nonsignificant. In 15 men with multiple peripheral fractures, trabecular spacing and distribution remained increased after adjustment for aBMD. Thus, in men, vertebral fractures and their severity are associated with impaired cortical bone, even after adjustment for aBMD. The association between peripheral fractures and bone microarchitecture was weaker and nonsignificant after adjustment for aBMD. Thus bone microarchitecture may be a determinant of bone fragility in men, which should be investigated in prospective studies. © 2011 American Society for Bone and Mineral Research.     

Effect of implanted bisphosphonate-enriched cement on the trabecular microarchitecture of bone in a rat model using micro-computed tomography

Purpose

Bisphosphonates (BPs) are antiresorptive drugs typically used to inhibit bone resorption. The latest reports show that BPs play an important role in not only achieving better bone mineral density but also in improving bone microarchitecture. The mechanism of action of the BPs is complex and multifactorial. We tried to determine whether there are any changes in the microarchitectural bone structure during local use of BP (Pamifos 60). The aim of this study was to see if BP-enriched cement used in rat models had positive effects on bone formation.

Methods

Research was performed on 40 adult male Wistar rats that were divided into four groups: two control groups and two experimental groups. Rats in the experimental groups were implanted with BP-enriched cement into the bone, while the control group rats were implanted with clean bone cement (without BP). Micro-computed tomography was applied for the investigation of trabecular microarchitecture of the proximal physis of the tibial bone in all animals three and six weeks after surgery. In all microCT images variables such as bone volume density (BV/TV), trabecular thickness (TbTh), trabecular separation (TbSp) and trabecular number (TbN) were used to describe trabecular bone morphometry.

Results

The major finding of this study is that using BP-enriched cement results in distinct changes in bone microarchitecture. We showed that local use of pamidronate (Pamifos 60) in orthopaedic cement had a positive effect on bone formation. It significantly changed three variables. We noticed increasing bone volume fraction and trabecular thickness together with decreasing trabecular separation.

Conclusion

In this paper we demonstrate the efficacy of using BP-enriched cement in vitro in the tibiae of rats. Our most significant finding based on micro-CT picture analysis allows us to start further work on more suitable applications of BP-enriched cement in humans. We believe that future successful experiments will facilitate potential use of BP-enriched cement in clinical applications.     

Validation of Bone Density and Microarchitecture Measurements of the Load-Bearing Femur in the Human Knee Obtained Using In Vivo HR-pQCT Protocol

High resolution peripheral quantitative computed tomography (HR-pQCT) was designed to study bone mineral density (BMD) and microarchitecture in peripheral sites at the distal radius and tibia. With the introduction of the second generation HR-pQCT scanner (XtremeCT II, Scanco Medical) that has a larger, longer gantry it is now possible to study the human knee in vivo using HR-pQCT. Previous validation of HR-pQCT measurements at the distal radius and tibia against micro-CT is not representative of the knee because the increased cross-sectional area, greater amount of soft tissue surrounding the scan region, and different imaging protocol result in potentially increased beam hardening effects and photon scatter and different signal-to-noise ratio. The objective of this study is to determine the accuracy of density and microarchitecture measurements in the human knee measured by HR-pQCT using an in vivo protocol. Twelve fresh-frozen cadaver knees were imaged using in vivo HR-pQCT (60.7 µm) protocol. Subsequentially, distal femurs were extracted and imaged using a higher resolution (30.3 µm) ex vivo protocol, replicating micro-CT imaging. Scans were registered so that agreement of density and bone microarchitecture measurements could be determined using linear regression and Bland-Altman plots. All density and microarchitecture outcomes were highly correlated between the 2 protocols (R² > 0.89) albeit with statistically significant differences between absolute measures based on paired t tests. All parameters showed accuracy between 4.5% and 8.7%, and errors were highly systematic, particularly for trabecular BMD and trabecular thickness (R² > 0.93). We found that BMD and microarchitecture measurements in the distal femur obtained using an in vivo HR-pQCT knee protocol contained systematic errors, and accurately represented measurements obtained using a micro-CT equivalent imaging protocol. This work establishes the validity and limitations of using HR-pQCT to study the BMD and microarchitecture of human knees in future clinical studies.     

A Morphometric Comparison of Trabecular Structure of Human Ilium Between Microcomputed Tomography and Conventional Histomorphometry

Recently, an imaging technique using microcomputed tomography (micro-CT) has emerged as a method for nondestructively assessing the microarchitecture of unprocessed surgical bone biopsy specimens. Using micro-CT, two-dimensional (2D) axial images were obtained from undecalcified transiliac bone biopsies which were taken from 15 patients with various metabolic bone diseases. Total area, bone area, and bone perimeter were determined, from which the bone volume (BV/TV), trabecular thickness (Tb.Th), trabecular number (Tb.N), and trabecular separation (Tb.Sp) were calculated semiautomatically and instantaneously. To evaluate the validity of this technique as a useful tool, the results were compared with those obtained from conventional histomorphometry. There were significant correlations between the two techniques for all parameters, with correlation coefficients ranging from 0.759 (Tb.N, P < 0.005) to 0.949 (BV/TV, P < 0.0001). Different resolutions seem to lead to major differences in perimeter values measured by the two methods. These factors may explain why the correlation coefficients of Tb.N and Tb.Th estimated from the perimeter and area is lower than that of BV/TV. Our results show that the micro-CT based on 2D images is a useful tool for imaging and nondestructively quantifying the microarchitecture of trabecular bone in unprocessed surgical bone specimens.     

Advanced imaging assessment of bone fragility in glucocorticoid-induced osteoporosis

Advanced bone imaging techniques provide structural information, beyond bone mineral density (BMD), and growing evidence indicates that BMD only partially explains bone strength and fracture resistance. Assessing glucocorticoid-induced osteoporosis (GIO) is important, especially the documentation of glucocorticoid (GC) impact on trabecular and cortical bone and on macro and microstructural features. Advanced methods for assessing macrostructure of bone include volumetric quantitative computed tomography (vQCT), high-resolution computed tomography (hrCT), and high-resolution magnetic resonance imaging (hrMRI). The methods for assessing bone microstructure include micro computed tomography (μCT) and micro magnetic resonance imaging (μMRI). Many advanced imaging techniques have been used in vitro and in vivo to examine structural effects of GIO in animals and in humans, and these applications are explored in this review. In human in vitro studies, investigators have used standard bone histomorphometry and μCT to compare trabecular microarchitecture and bone remodeling in postmenopausal women and in males with GIO, and have found that high-dose GC produces dramatic bone loss, accompanied by major reduction in trabecular connectivity and increases in trabecular perforations. In animal studies, investigators have used standard histomorphometry along with pQCT, vQCT, hrMRI or μCT to examine GIO in a variety of animal models including rats, minipigs and sheep. They generally have found excellent relationships between treatment-induced structural changes assessed by these advanced imaging techniques and changes in BMD and biomechanical properties. They also have examined various therapeutic interventions in animals and monitored their efficacy using quantitative imaging methods. In human in vivo studies, investigators have serially examined postmenopausal women and males with GIO in order to assess the extent of skeletal deterioration and to determine the best advanced measures of BMD and structure, with which to monitor disease activity and therapeutic response, and to predict fracture risk. They generally have found that bone density and structural measures obtained by pQCT, vQCT and hrMRI contributed substantially to understanding the skeletal effects of glucocorticoids and to predicting the risk of fracture in human GIO. These animal and human applications, illustrating advanced imaging in GIO, are still in early stages of development. However, as discussed in this review, the novelty and power of the imaging approaches are compelling, and their utility is promising.     

Quantification of the roles of trabecular microarchitecture and trabecular type in determining the elastic modulus of human trabecular bone.

The roles of microarchitecture and types of trabeculae in determining elastic modulus of trabecular bone have been studied in microCT images of 29 trabecular bone samples by comparing their Young's moduli calculated by finite element analysis (FEA) with different trabecular type-specific reconstructions. The results suggest that trabecular plates play an essential role in determining elastic properties of trabecular bone. INTRODUCTION: Osteoporosis is an age-related disease characterized by low bone mass and architectural deterioration. Other than bone volume fraction (BV/TV), microarchitecture of bone is also believed to be important in governing mechanical properties of trabecular bone. We quantitatively examined the role of microarchitecture and relative contribution of trabecular types of individual trabecula in determining the elastic property of trabecular bone. MATERIALS AND METHODS: Twenty-nine human cadaveric trabecular bone samples were scanned at 21-mum resolution using a microCT system. Digital topological analysis (DTA) consisting of skeletonization and classification was combined with a trabecular type-specific reconstruction technique to extract the skeleton and identify topological type of trabeculae of the original trabecular bone image. Four different microCT-based finite element (FE) models were constructed for each specimen: (1) original full voxel; (2) skeletal voxel; (3) rod-reconstructed, preserving rod volume and plate skeleton; and (4) plate-reconstructed, preserving plate volume and rod skeleton. For each model, the elastic moduli were calculated under compression along each of three image-coordinate axis directions. Plate and rod tissue fractions directly measured from DTA-based topological classification were correlated with the elastic moduli computed from full voxel model. RESULTS: The elastic moduli of skeleton models were significantly correlated with those of full voxel models along all three coordinate axes (r(2) = 0.38 approximately 0.53). The rod-reconstructed model contained 21.3% of original bone mass and restored 1.5% of elastic moduli, whereas the plate-reconstructed model contained 90.3% of bone mass and restored 53.2% of elastic moduli. Plate tissue fraction showed a significantly positive correlation (r(2) = 0.49) with elastic modulus by a power law, whereas rod tissue fraction showed a significantly negative correlation (r(2) = 0.42). CONCLUSIONS: These results quantitatively show that the microarchitecture alone affects elastic moduli of trabecular bone and trabecular plates make a far greater contribution than rods to the bone's elastic behavior.