The 3D-based scaling index algorithm: a new structure measure to analyze trabecular bone architecture in high-resolution MR images in vivo

Introduction The purpose of this study was to obtain different structure measures as the three-dimensional (3D)-based scaling index method (SIM) and standard two-dimensional (2D) bone histomorphometric parameters from high-resolution (HR) magnetic resonance (MR) images of the distal radius and to compare these parameters with bone mineral density (BMD) in their diagnostic performance to differentiate postmenopausal patients with and without vertebral fractures.Methods Axial HR-MR images of the distal radius were obtained at 1.5 T in 40 postmenopausal women (17 with osteoporotic spine fractures and 23 controls). Trabecular microarchitecture analysis was performed using the new structure measure , derived from the SIM, as well as standard morphological 2D parameters. BMD of the spine was obtained using quantitative computed tomography (QCT). Receiver operating characteristic (ROC) analyses were used to determine diagnostic performance in differentiating both groups. Results were validated by bootstrapping techniques.Results Significant differences between both patient groups were obtained using , 2D parameters, and spine BMD (p<0.05). In comparison with the 2D texture parameters [area under the curve (AUC) up to 0.67], diagnostic performance was significantly higher for (AUC=0.85; p<0.05). There was a trend for a higher AUC value for compared with BMD of the spine (AUC=0.71; p=0.81).Conclusion yielded a robust measure of trabecular bone microarchitecture for HR-MR images of the radius, which significantly improved the diagnostic performance in differentiating postmenopausal women with and without osteoporotic spine fractures compared with standard 2D bone histomorphometric parameters. This 3D characterization of trabecular microarchitecture may provide a new approach to better assess the strength of human cancellous bone using HR-MR image data.This work was supported by the grant “Tandem-Projekt: Verbesserung der Diagnose von Osteoporose” of the Max-Planck-Society.     

MicroCT evaluation of normal and osteoarthritic bone structure in human knee specimens.

Although trabecular bone structure has been evaluated, variation with knee compartment and depth from joint surface is not completely understood. Cadaver knees were evaluated with microcomputed tomography analysis for these variations. Objective differences were compared between: medial vs. lateral compartments; femoral vs. tibial bone; and normal vs. arthritic knees. Depth dependent changes in the parameters were observed for the first 6 mm of the cores in normal knees: BV/TV, Tb.N and Conn.D gradually decrease, while Tb.Sp and SMI increase. In the first 6 mm of the normal tibia BV/TV, Tb.N, and Tb.Th are greater than in the femur on both the medial and lateral compartments while Tb.Sp, SMI, and Conn.D are lower. The medial compartment values for BV/TV, Tb.N, Tb.Th and Conn.D are generally greater than for the lateral in both the femur and tibia while Tb.Sp and SMI are lower. In comparison of normal vs. arthritic knees significant differences are observed in the first 6 mm of the medial tibia. With arthritis BV/TV and Tb.Th are lower, while SMI and Tb.Sp are higher. Tb.N and Conn.D show no statistically significant difference. The bone structure variations are, thus, most prominent in the first 6 mm of depth and medial compartment bone is generally more structurally sound than lateral. Severely arthritic bone changes are most prominent in the medial compartment of the tibia and bone structure is less sound in severe arthritis.     

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.     

Does Quantitative Ultrasound of Bone Reflect More Bone Mineral Density Than Bone Microarchitecture?

Relationships among quantitative ultrasound of bone (QUS), bone mineral density (BMD) and bone microarchitecture have been poorly investigated in human calcaneus. .Twenty-four specimens, from 12 men and 12 women (mean age 78 ± 10 years; range 53–93), removed from cadavers were studied. The feet were axially sectioned above the ankle. Two variables were measured for QUS (Achilles®, Lunar): broadband ultrasound attenuation (BUA) and speed of sound (SOS). A third variable, the stiffness index (SI), which is a combination of both BUA and SOS, was also calculated. BMD (a lateral view) was measured on a QDR 2000 densitometer (Hologic). Bone microarchitecture was assessed by computed tomography (CT) using a conventional CT-system. Fifteen sagittal sections (1 mm in width and 2 mm apart) were selected for CT. Methods used for characterizing bone microarchitecture consisted in structural (trabecular network characterization) and a fractal analyses. The relationships between QUS and bone microarchitecture were assessed by simple linear regression analysis with and without adjustment for BMD (partial correlation) and by backward stepwise regression analysis. Strong relationships were found between BMD and QUS. Adjusted r² values were 0.545 for SOS and 0.717 for SI. Two microarchitectural variables were also significantly correlated with both SOS and SI: apparent trabecular separation (App Tr Sp) and trabecular bone pattern factor (App TBPF). After adjustment for BMD few correlations between QUS and microarchitectural variables were always significant. Adjusted squared semipartial coefficients of correlation (rs_p²) values between SOS and bone microarchitecture were 6%, 6.8%, 13.2% and 4.6% for App BV/TV, App Tr Sp, App TBPF and fractal dimension (FD), respectively. For SI, corresponding figures were 3.7%, 4.1%, 5.2% and 3.2%. Backward stepwise regression analysis using BMD and microarchitecture showed a slight increase of r² values that varied from 8.4% for SI to 17.8% for SOS, compared with BMD alone. The current study suggests that although BMD is a major determinant of acoustic properties of human calcaneus, significant density independent relationships with bone microarchitecture should also be taken into account.     

Trabecular volumetric bone mineral density is associated with previous fracture during childhood and adolescence in males: The GOOD study

Areal bone mineral density (aBMD) measured with dual‐energy X‐ray absorptiometry (DXA) has been associated with fracture risk in children and adolescents, but it remains unclear whether this association is due to volumetric BMD (vBMD) of the cortical and/or trabecular bone compartments or bone size. The aim of this study was to determine whether vBMD or bone size was associated with X‐ray‐verified fractures in men during growth. In total, 1068 men (aged 18.9 ± 0.6 years) were included in the population‐based Gothenburg Osteoporosis and Obesity Determinants (GOOD) Study. Areal BMD was measured by DXA, whereas cortical and trabecular vBMD and bone size were measured by peripheral quantitative computerized tomography (pQCT). X‐ray records were searched for fractures. Self‐reported fractures in 77 men could not be confirmed in these records. These men were excluded, resulting in 991 included men, of which 304 men had an X‐ray‐verified fracture and 687 were nonfracture subjects. Growth charts were used to establish the age of peak height velocity (PHV, n = 600). Men with prevalent fractures had lower aBMD (lumbar spine 2.3%, p = .005; total femur 2.6%, p = .004, radius 2.1%, p < .001) at all measured sites than men without fracture. Using pQCT measurements, we found that men with a prevalent fracture had markedly lower trabecular vBMD (radius 6.6%, p = 7.5 × 10^?8; tibia 4.5%, p = 1.7 × 10^?7) as well as a slightly lower cortical vBMD (radius 0.4%, p = .0012; tibia 0.3%, p = .015) but not reduced cortical cross‐sectional area than men without fracture. Every SD decrease in trabecular vBMD of the radius and tibia was associated with 1.46 [radius 95% confidence interval (CI) 1.26–1.69; tibia 95% CI 1.26–1.68] times increased fracture prevalence. The peak fracture incidence coincided with the timing of PHV (±1 year). In conclusion, trabecular vBMD but not aBMD was independently associated with prevalent X‐ray‐verified fractures in young men. Further studies are needed to determine if assessment of trabecular vBMD could enhance prediction of fractures during growth in males. © 2010 American Society for Bone and Mineral Research     

Effect of trabecular bone contour on ultimate strength of lumbar vertebra after bilateral ovariectomy in rats

To test the hypothesis that the effect of trabecular microarchitecture on bone strength varies with the duration of estrogen loss, we evaluated the relationship between three-dimensional (3D) parameters for trabecular microarchitecture and bone minerals with the compressive load of the lumbar vertebra in rats. Female Sprague-Dawley rats (n = 190) were divided into 19 groups. Ten rats were killed at day 0. Half of the remaining rats underwent bilateral ovariectomy (ovx), and the others were subjected to sham surgery. Ten rats from each group were killed at 3, 7, 11, 14, 28, 42, 56, 70, and 84 days postsurgery. Urinary deoxypyridinoline and serum osteocalcin increased significantly in the ovx group from days 28 and 11, respectively, compared with the sham group. Bone mineral content (BMC) and bone mineral density (BMD) of the fifth lumbar body diminished from days 42 and 84, respectively, compared with the sham group. In ovx rats, trabecular bone volume (BV/TV), measured using 3D images of microcomputed tomography, diminished from day 28 compared with both baseline control and sham. The trabecular bone pattern factor (TBPf) and structure model index (SMI) increased from day 28 in the ovx group compared with both baseline control and sham. Ultimate compression loads diminished at day 28 compared with baseline control and decreased progressively thereafter. Neither of these parameters changed in the sham group during the same period. Within 4 weeks post-ovx, TBPf, SMI, and BV/TV correlated with load (p < 0.01). BMC and BMD correlated with load from 6 weeks post-ovx (p < 0.01). Stepwise regression analysis showed that TBPf was the most significant determinant of load within 4 weeks post-ovx (coefficient of determination [R²] = 0.669; p < 0.01). SMI correlated with TBPf (R² = 0.968; p < 0.01). Moreover, R² for ultimate load indicated higher values of 0.975 with TBPf and SMI. However, BMC was the most significant determinant of load from 6 weeks post-ovx (R² = 0.511; p < 0.01), as it was in the sham group. These data suggest that changes in trabecular bone contour with increased bone turnover are critical for reducing lumbar bone strength during the early post-ovx period in rats.     

Localization of regional forearm bone loss from high resolution computed tomographic images

The precise site of bone loss was evaluated in early postmenopausal women using high resolution computed tomographic (CT) images of forearm measurements. A procedure was devised to quantitate trabecular and subcortical bone density of the distal radius, cortical bone density of the diaphyseal radius, and cortical wall thickness at both measuring sites. Twenty women (mean age 52 years, time since menopause 1 to 4 years) were examined twice at one-year intervals to determine the yearly change of the above mentioned bone parameters. Trabecular bone and subcortical bone showed the same density reduction of 7 mg/cm³ per year. Cortical bone density remains unchanged and no increase in porosity can be seen. For early postmenopausal women the reduction of bone mass (BMC) in the diaphysis of the radius is, therefore, due to a thinning of the cortical wall. This is in accordance with the observed average loss of wall thickness of 0.04 mm per year. The non-invasive determination of the precise localization of bone changes in individual patients should be of value in the assessment of the severity of osteoporosis. Furthermore it has potential in the evaluation of the efficacy of therapeutic procedures in the various disease states.     

In vivo application of 3D-line skeleton graph analysis (LSGA) technique with high-resolution magnetic resonance imaging of trabecular bone structure

Over the last several years magnetic resonance (MR) imaging has emerged as a means of measuring in vivo 3D trabecular bone structure. In particular, MR based diagnosis could be used to complement standard bone mineral density (BMD) methods for assessing osteoporosis and evaluating longitudinal changes. The aim of this study was to demonstrate the feasibility of using the 3D-LSGA technique for the evaluation of trabecular bone structure of high-resolution MR images, particularly for assessing longitudinal changes, in vivo. First, the reproducibility of topological 3D-LSGA based measurements was evaluated in a set of seven volunteers, and coefficients of variations ranged from 3.5% to 6%. Second, high-resolution MR images of the radius in 30 postmenopausal women from a placebo controlled drug study (Idoxifene), divided into placebo (n=9) and treated (n=21) groups, were obtained at baseline (BL) and after 1 year of treatment (follow-up, FU). In addition, dual X-ray absorptiometry (DXA) measures of BMD were obtained in the distal radius. Standard morphological measurements based on the mean intercept length (MIL) technique as well as 3D-LSGA based measurements were applied to the 3D MR images. Significant changes from BL to FU were detected, in the treated group, using the topological 3D-LSGA based measurements, morphological measures of volume of connected trabeculae and App Tb.N from MIL analysis. The duration of the study was short, and the number of patients remaining in the study was small, hence these results cannot be interpreted with regard to a true therapeutic response. Furthermore, the site (wrist) and the drug (idoxifene) are not optimal for follow-up study. However, this paper demonstrated the feasibility of using 3D-LSGA based evaluation coupled with in vivo high-resolution MR imaging as a complementary approach for the monitoring of trabecular bone changes in individual subjects.     

Degree and Distribution of Mineralization in the Human Mandibular Condyle

The degree of mineralization of bone (DMB) in the mandibular condyle reflects the age and remodeling rate of the bone tissue. Quantification of DMB facilitates a better understanding of possible effects of adaptive remodeling on mineralization of the condyle and its possible consequences for its mechanical quality. We hypothesized differences in the degree and distribution of mineralization between trabecular and cortical bone and between various cortical regions. Microcomputed tomography was used to measure mineralization in 10 human mandibular condyles. Mean DMB was higher in cortical (1,045 mg hydroxyapatite/cm³) than in trabecular bone (857 mg/cm³) and differed significantly between cortical regions (anterior 987 mg/cm³, posterior 1,028 mg/cm³, subchondral 1,120 mg/cm³). The variation of DMB distribution was significantly larger in the anterior cortex than in the posterior and subchondral cortex, indicating a larger amount of heterogeneity of mineralization anteriorly. Within the cortical bone, DMB increased with the distance from the cortical canals to the periphery. Similarly, the DMB of trabecular bone increased with the distance from the surface of the trabeculae to their cores. It was concluded that the rate of remodeling differs between condylar trabecular and cortical bone and between cortical regions and that DMB is not randomly distributed across the bone. The difference in DMB between condylar cortical and trabecular bone suggests a large difference in Young’s modulus.     

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.     

Analysis of Trabecular Bone Structure with Multidetector Spiral Computed Tomography in a Simulated Soft-Tissue Environment

We investigated the influence of soft tissue (ST) on image quality by high-resolution multidetector computed tomography (MDCT) scans and assessed the effect of surrounding ST on the quantification of trabecular bone structure. Eight bone cores obtained from human proximal femoral heads discarded during hip replacement surgery were scanned with micro-computed tomography (μCT) as well as with MDCT both without (w/o) and with (w) simulated surrounding ST, where a phantom imitated a human torso. Signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were measured in all scans. Apparent trabecular bone structure parameters were calculated and compared to similar parameters obtained in coregistered sections of the μCT scans. Residual errors were calculated as root-mean-square (RMS) errors relative to the μCT measurements. Compared to μCT results, trabecular structure parameters were overestimated by MDCT both w and w/o ST. SNR and CNR were significantly higher in the scans w/o ST. Significant correlations between μCT and MDCT results were found for bone fraction (r = 0.90 w/o ST, r = 0.84 w ST), trabecular number, and separation. RMS ranged from 10% to 15% for MDCT w/o ST and from 10% to 17% for MDCT w ST. Only bone fraction showed significantly different RMS and correlations for scans w/o vs. w ST (P < 0.05). This study showed that MDCT is able to visualize trabecular bone structure in an in vivo-like setting at skeletal sites within the torso such as the proximal femur. Even though ST scatter compromises image quality substantially, the major characteristics of the trabecular network can still be appreciated and quantified. Funding source Seed grant by the Department of Radiology, University of California, San Francisco, CA, USA     

Does thoracic or lumbar spine bone architecture predict vertebral failure strength more accurately than density?

Summary Trabecular bone microstructure was studied in 6 mm bone biopsies taken from the 10th thoracic and 2nd lumbar vertebra of 165 human donors and shown to not differ significantly between these sites. Microstructural parameters at the locations examined provided only marginal additional information to quantitative computed tomography in predicting experimental failure strength. Introduction It is unknown whether trabecular microstructure differs between thoracic and lumbar vertebrae and whether it adds significant information in predicting the mechanical strength of vertebrae in combination with QCT-based bone density. Methods Six mm cylindrical biopsies taken at mid-vertebral level, anterior to the center of the thoracic vertebra (T) 10 and the lumbar vertebra (L) 2 were studied with micro-computed tomography (μCT) in 165 donors (age 52 to 99 years). The segment T11-L1 was examined with QCT and tested to failure using a testing machine. Results The correlation of microstructural properties was moderate between T10 and L2 (r ≤ 0.5). No significant differences were observed in the microstructural properties between the thoracic and lumbar spine, nor were sex differences at T10 or L2 observed. Cortical/subcortical density of T12 (r ² = 48%) was more strongly correlated with vertebral failure stress than trabecular density (r ² = 32%). BV/TV (of T10) improved the prediction by 52% (adjusted r ²) in a multiple regression model. Conclusion Microstructural properties of trabecular bone biopsies displayed a high degree of heterogeneity between vertebrae but did not differ significantly between the thoracic and lumbar spine. At the locations examined, bone microstructure only marginally improved the prediction of structural vertebral strength beyond QCT-based bone density.     

密云地区腰椎定量CT骨密度测量分析

目的 探讨腰椎QCT骨密度测量的峰值骨量,骨量丢失,骨质疏松症发病率, 为临床诊断和治疗提供依据。方法 整理在本院进行腰椎QCT骨密度测量的患者222例。其中：男性97例,年龄30~87岁,平均63.3岁;女性125例,年龄23~87岁,平均63.1岁。按照世界卫生组织提出新的年龄分段方法,分为3组：青年组＜44岁、45＜中年组＜59岁、老年组＞60岁。利用SPSS19.0对数据进行处理,计量资料采用 方式表示,偏相关分析、线性回归分析、独立样本T检验、多因素方差分析检验,P＜0.05表示差异有显著性,计数资料采用卡方检验。结果 男女性峰值骨量出现于青年组,女性峰值高于男性;中年后骨量开始丢失,老年后女性较男性丢失明显（P＜0.05）;女性骨质疏松症发病率高于男性。结论 QCT腰椎骨密度测量精准、简便、快捷具有广泛的临床应用价值;对人体骨量的变化,诊断、预防骨质疏松症;预测骨质疏松性骨折起着重要作用     

Severity of vertebral fracture reflects deterioration of bone microarchitecture

Introduction Bone microarchitecture, a component of bone strength, is generally measured on transiliac bone biopsy samples. The objective of this study was to determine whether assessment of four grades of vertebral fracture severity could serve as a noninvasive surrogate marker for trabecular bone volume and microarchitecture. Methods Baseline vertebral fracture severity was determined by semiquantitative assessment of spine radiographs from 190 postmenopausal women with osteoporosis. Bone-structure indices were obtained by 2D histomorphometry and 3D microcomputed tomography (CT) analyses. Significance of differences was determined after adjusting for age, height, and lumbar spine bone mineral density. Results There were significant (P < 0.05) trends in decreasing bone volume, trabecular number, and connectivity, and increasing trabecular separation with greater vertebral fracture severity. Histomorphometric bone volume was 25 and 36% lower (P < 0.05) in women with moderate and severe fractures than in women with no fractures, respectively. Compared with women without fractures, women with mild, moderate, and severe fractures had lower (P < 0.05) microCT bone volume (23, 30, and 51%, respectively). Conclusions Microarchitectural deterioration was progressively worse in women with increasing severity of vertebral fractures. We conclude that assessment of vertebral fracture severity is an important clinical tool to evaluate the severity of postmenopausal osteoporosis.     

中老年人腹主动脉钙化与腰椎骨密度的相关性研究

目的研究中老年人腹主动脉钙化(AAC)与腰椎定量CT(QCT)骨密度(BMD)的相关性。方法纳入2013年至2016年间招募的593名40~80岁(男性230人,女性363人)的健康志愿者测量受检者身高、体质量、腰围,计算体重指数(BMI);进行腰椎QCT骨密度测量,将原始图像传至图像后处理工作站,采用Mindways QCT pro软件,分别测量L1-3椎体骨密度。应用Image J软件测量腹主动脉钙化面积比。结果男、女性AAC患病率分别约为45.65%、28.37%;与无AAC组比较,男性、女性AAC组年龄更大,并且与腰椎BMD的差异均有统计学意义(P均0.05);男女腰椎BMD均与年龄呈负相关(r=-0.49、r=-0.73,P0.05),与BMI均无明显相关性(r=0.02、r=0.01,P0.05);男、女性AAC均与年龄呈正相关(r=0.39、r=0.42,P0.05),与BMI均无明显相关性(r=-0.03、r=-0.03,P0.05);男性BMD与AAC无明显相关性(P=0.15),女性BMD与AAC呈低度负相关(r=-0.32,P0.05),校正年龄以后,女性BMD与AAC也无明显相关性(P=0.08)。结论年龄为腹主动脉钙化和骨质疏松发病的共同独立的危险因素,校正年龄后,男性、女性腰椎BMD与AAC均无显著相关性。     

Cnaical significance of changes in cortital and trabeular bone density after menopause

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Influence of bone adaptation on tendon‐to‐bone healing in bone tunnel after anterior cruciate ligament reconstruction in a rabbit model

Anterior cruciate ligament (ACL) reconstruction with placement of grafted tendon in bone tunnel is a common surgical procedure. Bone tunnel creation may result in stress shielding of postero‐lateral regions of tibial tunnel. The present study was designed to characterize the changes of peri‐graft bone and compare with tendon‐to‐bone (T‐B) healing in spatial and temporal manners after ACL reconstruction in rabbit. Surgical reconstruction using digital extensor tendon in bone tunnel was performed on 48 rabbits. Twelve rabbits were sacrificed at 0, 2, 6, and 12 weeks postoperatively for radiological and histological examinations. Bone mass and microarchitecture at the anterior, posterior, medial, and lateral regions of tunnel wall at distal femur and proximal tibia were evaluated. Using peripheral quantitative computed tomography, a 26, 22, and 42% decrease in bone mineral density (BMD) relative to baseline was present in the medial region of the femoral tunnel and the posterior and lateral regions of the tibial tunnel, respectively, at week 12 postoperatively (p < 0.05). It was accompanied by a decrease in trabecular number and increase in trabecular spacing, the shift of platelike to rodlike trabeculae, and loss of anisotropy under micro‐computed tomography evaluation. This finding was echoed by histology showing increased osteoclastic activities and poor T‐B healing in these regions. In conclusion, the postoperative bone loss and associated poor T‐B healing was region‐dependent, which may result from adaptive changes after tunnel creation. © 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 27:1447–1456, 2009