Cortical parameters predict bone strength at the tibial diaphysis,but are underestimated by HR-pQCT and μCT compared to histomorphometry

Cortical bone and its microstructure are crucial for bone strength, especially at the long bone diaphysis. However, it is still not well-defined how imaging procedures can be used as predictive tools for mechanical bone properties. This study evaluated the capability of several high-resolution imaging techniques to capture cortical bone morphology and assessed the correlation with the bone's mechanical properties. The microstructural properties (cortical thickness [Ct.Th], porosity [Ct.Po], area [Ct.Ar]) of 11 female tibial diaphysis (40–90 years) were evaluated by dual-energy X-ray absorptiometry (DXA), high-resolution peripheral-quantitative-computed-tomography (HR-pQCT), micro-CT (μCT) and histomorphometry. Stiffness and maximal torque to failure were determined by mechanical testing. T-Scores determined by DXA ranged from 0.6 to −5.6 and a lower T-Score was associated with a decrease in Ct.Th (p ≤ 0.001) while the Ct.Po (p ≤ 0.007) increased, and this relationship was independent of the imaging method. With decreasing T-Score, histology showed an increase in Ct.Po from the endosteal to the periosteal side (p = 0.001) and an exponential increase in the ratio of osteons at rest to those after remodelling. However, compared to histomorphometry, HR-pQCT and μCT underestimated Ct.Po and Ct.Th. A lower T-Score was also associated with significantly reduced stiffness (p = 0.031) and maximal torque (p = 0.006). Improving the accuracy of Ct.Po and Ct.Th did not improve prediction of the mechanical properties, which was most closely related to geometry (Ct.Ar). The ex-vivo evaluation of mechanical properties correlated with all imaging modalities, with Ct.Th and Ct.Po highly correlated with the T-Score of the tibial diaphysis. Cortical microstructural changes were underestimated with the lower resolution of HR-pQCT and μCT compared to the histological ‘gold standard’. The increased accuracy did not result in an improved prediction for local bone strength in this study, which however might be related to the limited number of specimens and thus needs to be evaluated in a larger collective.     

Collagen proton fraction from ultrashort echo time magnetization transfer (UTE‐MT) MRI modelling correlates significantly with cortical bone porosity measured with micro‐computed tomography (μCT)

Intracortical bone porosity is a key microstructural parameter that determines bone mechanical properties. While clinical MRI visualizes the cortical bone with a signal void, ultrashort echo time (UTE) MRI can acquire high signal from cortical bone, thus enabling quantitative assessments. Magnetization transfer (MT) imaging combined with UTE‐MRI can indirectly assess protons in the bone collagenous matrix, which are inversely related to porosity. This study aimed to examine UTE‐MT MRI techniques to evaluate intracortical bone porosity. Eighteen human cortical bone specimens from the tibial and fibular midshafts were scanned using UTE‐MT sequences on a clinical 3 T MRI scanner and on a high‐resolution micro‐computed tomography (μCT) scanner. A series of MT pulse saturation powers (500°, 1000°, 1500°) and frequency offsets (2, 5, 10, 20, 50 kHz) were used to measure the macromolecular fraction (MMF) and macromolecular T₂ (T_2MM) using a two‐pool MT model. The measurements were made on 136 different regions of interest (ROIs). ROIs were selected at three cortical bone layers (from endosteum to periosteum) and four anatomical sites (anterior, mid‐medial, mid‐lateral, and posterior) to provide a wide range of porosity. MMF showed moderate to strong correlations with intracortical bone porosity (R = ?0.67 to ?0.73, p < 0.01) and bone mineral density (BMD) (R = +0.46 to +0.70, p < 0.01). Comparing the average MMF between cortical bone layers revealed a significant increase from the endosteum towards the periosteum. Such a pattern was in agreement with porosity reduction and BMD increase towards the periosteum. These results suggest that the two‐pool UTE‐MT technique can potentially serve as a novel and accurate tool to assess intracortical bone porosity.     

脊髓损伤早期及制动大鼠股骨干骺端的显微CT观察

背景：脊髓损伤后可引起损伤平面以下骨量大量丢失,导致骨质疏松。 目的：观察比较脊髓损伤及失用性制动模型大鼠股骨远端骨密度及骨微观结构的改变。 方法：将SD大鼠随机分为3组：对照组,切除T10椎板,不损伤硬膜及脊髓;脊髓损伤组,切除T10椎板后行Allen's法造成脊髓损伤;制动组,以大鼠双侧腿－尾缝合造成双下肢制动。10 d后取一侧尺、桡骨及股骨行骨密度检测,另一侧股骨行显微CT扫描。 结果与结论：脊髓损伤组与制动组大鼠股骨远端骨密度、骨矿物质含量、骨体积分数表、骨小梁厚度、骨皮质面积及厚度、骨小梁数量均低于对照组(P < 0.05 ),骨小梁结构模型指数、骨表面积体积比、骨小梁分离度均高于对照组;脊髓损伤组上述指标较制动组变化程度更显著(P < 0.05)。3组尺、桡骨密度差异无显著性意义。说明脊髓损伤及制动均可导致骨量丢失,在脊髓损伤早期损伤平面以下部位骨微观结构呈现骨质疏松明显改变,且程度比失用性因素严重。     

Enhancement of subchondral bone quality by alendronate administration for the reduction of cartilage degeneration in the early phase of experimental osteoarthritis

To evaluate the effects of alendronate (ALN) on the subchondral bone quality and cartilage degeneration in the early phase of experimental model of osteoarthritis after anterior cruciate ligament transaction (ACLT). Thirty male adult healthy Japanese white rabbits after right ACLT or sham operation were divided into three groups (n = 10 per group): Sham; ACLT + ALN [after ACLT, the rabbits were treated with ALN daily starting from 4 days after surgery (10 μg/kg/d subcutaneously)]; and ACLT + NS group (after ACLT, the rabbits were injected saline as a placebo). At 60 days postsurgery, specimens from the affected knees were harvested. Histological analysis (HE and Safranin-O staining) as well as Mankin score were carried out to assess the cartilage degradation. BMP-2 and MMP-13 immunohistochemistry were also performed to demonstrate the alterations of cartilage molecular metabolism. Subchondral bone quality was evaluated by bone mineral density (BMD) and microstructure histomorphometry assay. For bone mineral density evaluation, 1/4 distal femurs, medial and lateral regions of femoral condylus were scanned with dual X-ray absorptiometry to assess the subchondral bone mass. Giemsa, von Kossa stain, and fluorescence technique for undecalcified bone section were carried out to examine the morphometry of the subchondral trabecular bone and subchondral plate. Histological and Mankin score analyses displayed that ALN treatment markedly reduced cartilage lesions and delayed the cartilage degeneration in OA joints. Immunohistochemistry assay further indicated that this cartilage-protective role of ALN was associated with elevating BMP-2 while inhibiting MMP-13 expression. BMD assessment demonstrated that ALN treatment significantly suppressed subchondral bone resorption. The results from histomorphometry assay of subchondral bone revealed that ALN treatment markedly increased the percent trabecular area (BV/TV), trabecular thickness (Tb.Th), and trabecular number (Tb.N). Moreover, both thickness and the porosity of the subchondral plate in ACLT + ALN group presented significantly higher than that in ACLT + NS group, while no significant difference was found between ACLT + ALN and Sham group. ALN plays an important role in cartilage protection in OA joints that is associated with the improvement of subchondral bone quality through reduction of subchondral bone resorption. ALN could be potentially used as a disease-modifying strategy to limit the progression of OA.     

Comparison of dental implant stabilities by impact response and resonance frequencies using artificial bone

PurposeWe compared implant stability as determined by the peak frequency from the impact response with the implant stability quotient (ISQ) by resonance frequency analysis (RFA) in various artificial bone conditions. The clinical bone conditions were simulated using an artificial bone material with different cortical thicknesses and trabecular densities.Materials and methodsThe artificial bone material was solid, rigid polyurethane. The polyurethane foam of 0.8 g/cm³ density was used for the cortical bone layer, and that of 0.08, 0.16, 0.24, 0.32, and 0.48 g/cm³ densities for the trabecular bone layer. The cortical bone material of 4 different thicknesses (1.4, 1.6, 1.8, and 2.0 mm) was attached to the trabecular bone with varying density. Two types of dental implants (10 and 13 mm lengths of 4.0 mm diameter) were placed into the artificial bone blocks. An inductive sensor was used to measure the vibration caused by tapping the adapter–implant assembly. The peak frequency of the power spectrum of the impact response was used as the criterion for implant stability. The ISQ value was also measured for the same conditions.ResultsThe stability, as measured by peak frequency (SPF) and ISQ value, increased as the trabecular density and the cortical density increased in linear regression analysis. The SPF and ISQ values were highly correlated with each other when the trabecular bone density and cortical bone thickness changed (Pearson correlation = 0.90, p < 0.01). The linear regression of the SPF with the cortical bone thickness showed higher goodness of fit (R² measure) than the ISQ value with the cortical bone thickness. The SPF could differentiate implantation conditions as many as the ISQ value when the trabecular bone density and the cortical density changed. However, the ISQ value was not consistent with the general stability tendency in some conditions.ConclusionThe SPF showed better consistency and differentiability with implant stability than the ISQ value by resonance frequency analysis in the various implantation conditions.     

ClC-3基因过表达对小鼠骨量和骨结构的影响

 目的: 研究过表达电压门控氯通道家族蛋白成员3(voltage-gated chloride channel family protein 3,ClC-3)基因对小鼠骨骼的影响。方法: 3月龄雄性FVB小鼠用鼠尾基因检测法确定基因型后分为2组:野生型(WT)组和ClC-3过表达(ClC-3 transgene)组,每组各8只。分别测量2组小鼠体重,右侧胫骨长度和重量。取胫骨上段和中段进行脱钙,石蜡包埋,切片,HE染色后,采用骨形态计量学分析胫骨上段松质骨的骨小梁面积百分数(percent trabecular area,%Tb.Ar)、骨小梁数量(trabecular number,Tb.N)、骨小梁宽度(trabecular width,Tb.Wi)、骨小梁分离度(trabecular separation,Tb.Sp)和胫骨中段皮质骨的骨组织总面积(total tissue area,T.Ar)、皮质骨面积(cortical area,Ct.Ar)、皮质骨面积百分数(percent cortical area,%Ct.Ar)、骨髓腔面积(marrow area,Ma.Ar)、骨髓腔面积百分数(percent marrow area,%Ma.Ar)。结果: 小鼠经鼠尾基因检测后确认为野生型或ClC-3过表达型。与WT组相比,ClC-3 transgene组小鼠体重及胫骨长度重量均减小(P<0.05);松质骨的%Tb.Ar和Tb.Wi均减小(P<0.05),Tb.Sp增大(P<0.05),Tb.N的变化无统计学意义;皮质骨的T.Ar、Ct.Ar和%Ct.Ar均减小(P<0.05),%Ma.Ar增大(P<0.05),Ma.Ar的变化无统计学意义。结论: ClC-3过表达导致小鼠的皮质骨和松质骨骨量减少,骨结构变差,提示ClC-3可能参与了骨形成和/或骨吸收。     

Bi‐component T2* analysis of bound and pore bone water fractions fails at high field strengths

Osteoporosis involves the degradation of the bone's trabecular architecture, cortical thinning and enlargement of cortical pores. Increased cortical porosity is a major cause of the decreased strength of osteoporotic bone. The majority of cortical pores, however, are below the resolution limit of MRI. Recent work has shown that porosity can be evaluated by MRI‐based quantification of bone water. Bi‐exponential T₂* fitting and adiabatic inversion preparation are the two most common methods purported to distinguish bound and pore water in order to quantify matrix density and porosity. To assess the viability of T₂* bi‐component analysis as a method for the quantification of bound and pore water fractions, we applied this method to human cortical bone at 1.5, 3, 7 and 9.4 T, and validated the resulting pool fractions against micro‐computed tomography‐derived porosity and gravimetrically determined bone densities. We also investigated alternative methods: two‐dimensional T₁–T₂* bi‐component fitting by incorporation of saturation recovery, one‐ and two‐dimensional fitting of Carr–Purcell–Meiboom–Gill (CPMG) echo amplitudes, and deuterium inversion recovery. The short‐T₂* pool fraction was moderately correlated with porosity (R² = 0.70) and matrix density (R² = 0.63) at 1.5 T, but the strengths of these associations were found to diminish rapidly as the field strength increased, falling below R² = 0.5 at 3 T. The addition of the T₁ dimension to bi‐component analysis only slightly improved the strengths of these correlations. T₂*‐based bi‐component analysis should therefore be used with caution. The performance of deuterium inversion recovery at 9.4 T was also poor (R² = 0.50 vs porosity and R² = 0.46 vs matrix density). The CPMG‐derived short‐T₂ fraction at 9.4 T, however, was highly correlated with porosity (R² = 0.87) and matrix density (R² = 0.88), confirming the utility of this method for independent validation of bone water pools. Copyright © 2015 John Wiley & Sons, Ltd.     

Lumbar Vertebral Body Bone Microstructural Scaling in Small to Medium‐Sized Strepsirhines

Bone mass, architecture, and tissue mineral density contribute to bone strength. As body mass (BM) increases any one or combination of these properties could change to maintain structural integrity. To better understand the structural origins of vertebral fragility and gain insight into the mechanisms that govern bone adaptation, we conducted an integrative analysis of bone mass and microarchitecture in the last lumbar vertebral body from nine strepsirhine species, ranging in size from 42 g (Microcebus rufus) to 2,440 g (Eulemur macaco). Bone mass and architecture were assessed via µCT for the whole body and spherical volumes of interest (VOI). Allometric equations were estimated and compared with predictions for geometric scaling, assuming axial compression as the dominant loading regime. Bone mass, microarchitectural, and vertebral body geometric variables predominantly scaled isometrically. Among structural variables, the degree of anisotropy (Tb.DA) was the only parameter independent of BM and other trabecular architectural variables. Tb.DA was related to positional behavior. Orthograde primates had higher average Tb.DA (1.60) and more craniocaudally oriented trabeculae while lorisines had the lowest Tb.DA (1.25), as well as variably oriented trabeculae. Finally, lorisines had the highest ratio of trabecular bone volume to cortical shell volume (～3x) and while there appears to be flexibility in this ratio, the total bone volume (trabecular + cortical) scales isometrically (BM^1.23, r² = 0.93) and appears tightly constrained. The common pattern of isometry in our measurements leaves open the question of how vertebral bodies in strepsirhine species compensate for increased BM. Anat Rec, 2013. © 2013 Wiley Periodicals, Inc.     

Response of trabecular bone,thyroid C and follicular cells to synthetic salmon calcitonin in middle‐aged orchidectomized male rats

In contrast to studies in women, male osteoporosis is poorly understood and strictly related to advancing age. Among the first antiresorptive substances used in the prevention and treatment of osteoporosis is calcitonin (CT), a hypocalcemic hormone that potently inhibits osteoclastic bone resorption. Natural CT is produced and secreted by thyroid C‐cells. The other endocrine population of thyroid cells produces thyroid hormones (TH), which also affect bone turnover. The aim of this study was to evaluate the influence of salmon CT on trabecular bone microarchitecture with special reference to effects on the structure and function of both CT‐ and TH‐producing thyroid cells in orchidectomized (Orx) middle‐aged rats. Twenty‐four male Wistar rats aged 15 months were randomly divided into Orx and sham‐operated (SO) groups. One group of Orx animals received (s.c.) synthetic salmon CT (Orx + CT; 100 IU kg⁻¹ b.w.) subcutaneously every second day for 6 weeks. The second Orx group and SO rats were given the same volume of vehicle alone by the same schedule. Trabecular bone histomorphometrical parameters were: cancellous bone area (B.Ar), trabecular thickness (Tb.Th), trabecular number (Tb.N) and trabecular separation (Tb.Sp) were obtained with an ImageJ public‐domain image‐processing program. The peroxidase–antiperoxidase method was applied for localization of CT in C‐cells. Anti‐human CT antisera served as the primary antibodies. For immunohistochemical characterization of vascular endothelial growth factor (VEGF) in thyroid tissue, rabbit antisera against human VEGF, served as primary antibodies. CT‐immunopositive thyroid C‐cells, thyroid follicular epithelium, interstitium and colloid were evaluated morphometrically. Blood serum samples were analyzed for CT, osteocalcin (OC), and thyroxine (T₄), and calcium (Ca²⁺) concentration was determined in urine samples. Salmon CT application significantly increased B.Ar, TbTh and TbN, but markedly decreased Tb.Sp. Administration of exogenous CT significantly decreased mean volume (Vc) and relative volume density (Vv) of thyroid C‐cells in relation to both SO and Orx groups. The Vv of the colloid was higher, whereas the V_V of the follicular epithelium was lower after CT treatment compared with Orx alone. CT treatment markedly elevated serum CT, whereas serum OC, T₄ and urinary Ca²⁺ concentrations were lower than in the Orx group. These results indicate that salmon CT stimulates trabecular bone microarchitecture, strongly inhibits thyroid C‐cells and changes the structure of the thyroid gland, indicating hypoactivity.     

Effects of voluntary wheel running on goserelin acetate-induced bone degeneration

A common treatment option for many breast and prostate cancer patients is the use of a luteinizing hormone-releasing hormone agonist such as goserelin acetate (GA) which reduces sex hormone levels. This treatment, however, is associated with bone degeneration, and exercise has been suggested as a means of preventing this side effect. Little is known about the effects of low intensity, low volume exercise on GA-induced bone loss. The purpose of this study, therefore, was to investigate the effects of voluntary wheel running on bone architecture in growing male (M) and female (F) rats receiving GA treatment. Rats received an 8-week GA treatment or placebo (CON) and were either housed in cages equipped with voluntary running wheels (WR) or remained sedentary (SED) in standard cages throughout the experimental period. Following treatments, tibiae were excised and analyzed for cortical bone (cross-sectional volume, cortical volume, marrow volume, cortical thickness) and cancellous bone (bone volume/total volume, trabecular number, trabecular thickness, trabecular spacing) using micro-computed tomography. Treatment with GA resulted in a significant reduction in running wheel distances in both sexes throughout the study period (P < 0.05). GA treatment had no effect on cortical bone architecture in neither sex (P > 0.05). Cancellous bone degeneration, however, was observed in M and F SED + GA (P < 0.05). No significant differences were observed in M WR + GA animals in bone volume/total volume, trabecular number and trabecular spacing when compared to M SED + CON (P > 0.05). In F WR + GA, trabecular thickness did not differ from that of F SED + CON (P > 0.05), and trabecular spacing was found to be significantly lower than F SED + GA (P < 0.05). The current report indicates that 8 weeks of GA treatment promotes cancellous bone degeneration, and voluntary wheel running provides no clear osteoprotection in growing male and female rats.     

Trabecular architecture of the great ape and human femoral head

Studies of femoral trabecular structure have shown that the orientation and volume of bone are associated with variation in loading and could be informative about individual joint positioning during locomotion. In this study, we analyse for the first time trabecular bone patterns throughout the femoral head using a whole‐epiphysis approach to investigate how potential trabecular variation in humans and great apes relates to differences in locomotor modes. Trabecular architecture was analysed using microCT scans of Pan troglodytes (n = 20), Gorilla gorilla (n = 14), Pongo sp. (n = 5) and Homo sapiens (n = 12) in medtool 4.1. Our results revealed differences in bone volume fraction (BV/TV) distribution patterns, as well as overall trabecular parameters of the femoral head between great apes and humans. Pan and Gorilla showed two regions of high BV/TV in the femoral head, consistent with hip posture and loading during two discrete locomotor modes: knuckle‐walking and climbing. Most Pongo specimens also displayed two regions of high BV/TV, but these regions were less discrete and there was more variability across the sample. In contrast, Homo showed only one main region of high BV/TV in the femoral head and had the lowest BV/TV, as well as the most anisotropic trabeculae. The Homo trabecular structure is consistent with stereotypical loading with a more extended hip compared with great apes, which is characteristic of modern human bipedalism. Our results suggest that holistic evaluations of femoral head trabecular architecture can reveal previously undetected patterns linked to locomotor behaviour in extant apes and can provide further insight into hip joint loading in fossil hominins and other primates.     

Effect of bone density and cement morphology on biomechanical stability of tibial unicompartmental knee arthroplasty

BackgroundUnicompartmental knee arthroplasty (UKA) offers good long-term survivorship and superior kinematics and function compared with total knee arthroplasty (TKA). However, revision rates are higher with aseptic loosening representing a major cause. Biomechanical stability depends on cement penetration. The goal of this study was to analyze the influence of cement morphology and bone density on primary stability of tibial UKA under physiological loading conditions in human tibiae.MethodsThirty-six tibial trays were implanted in fresh-frozen human cadaver knees and tested for primary stability using dynamic compression–shear testing. Prior to implantation, bone density had been quantified for all 18 tibiae. Postoperatively, cement penetration has been assessed on frontal cuts based on eight predefined parameters. The influence of bone density and cement morphology on biomechanical stability was determined using correlation and linear regression analysis.ResultsMean failure load was 2691 ± 832.9 N, mean total cement thickness was 2.04 ± 0.37 mm, mean cement penetration was 1.54 ± 0.33 mm and mean trabecular bone mineral density (BMD) was 107.1 ± 29.3 mg/ml. There was no significant correlation between failure load and cement morphology (P > .05). Failure load was significantly positive correlated with trabecular BMD (r = 0.843; P < .0001) and cortical BMD (r = 0.432; P = .0136).ConclusionsSimulating physiological loading conditions, the failure load of tibial UKA is linearly dependent on the trabecular BMD. The observed parameters of cementation morphology seem capable of preventing failure at the bone–cement interface before inherent bone stability is reached. Further research is required to assess the usefulness of a preoperative assessment of bone quality for patient selection in UKA.     

Cortical and trabecular bone structure of the hominoid capitate

Morphological variation in the hominoid capitate has been linked to differences in habitual locomotor activity due to its importance in movement and load transfer at the midcarpal joint proximally and carpometacarpal joints distally. Although the shape of bones and their articulations are linked to joint mobility, the internal structure of bones has been shown experimentally to reflect, at least in part, the loading direction and magnitude experienced by the bone. To date, it is uncertain whether locomotor differences among hominoids are reflected in the bone microarchitecture of the capitate. Here, we apply a whole-bone methodology to quantify the cortical and trabecular architecture (separately and combined) of the capitate across bipedal (modern Homo sapiens), knuckle-walking (Pan paniscus, Pan troglodytes, Gorilla sp.), and suspensory (Pongo sp.) hominoids (n = 69). It is hypothesized that variation in bone microarchitecture will differentiate these locomotor groups, reflecting differences in habitual postures and presumed loading force and direction. Additionally, it is hypothesized that trabecular and cortical architecture in the proximal and distal regions, as a result of being part of mechanically divergent joints proximally and distally, will differ across these portions of the capitate. Results indicate that the capitate of knuckle-walking and suspensory hominoids is differentiated from bipedal Homo primarily by significantly thicker distal cortical bone. Knuckle-walking taxa are further differentiated from suspensory and bipedal taxa by more isotropic trabeculae in the proximal capitate. An allometric analysis indicates that size is not a significant determinate of bone variation across hominoids, although sexual dimorphism may influence some parameters within Gorilla. Results suggest that internal trabecular and cortical bone is subjected to different forces and functional adaptation responses across the capitate (and possibly other short bones). Additionally, while separating trabecular and cortical bone is normal protocol of current whole-bone methodologies, this study shows that when applied to carpals, removing or studying the cortical bone separately potentially obfuscates functionally relevant signals in bone structure.     

Characterization of trabecular bone density with ultra‐short echo‐time MRI at 1.5, 3.0 and 7.0 T – comparison with micro‐computed tomography

The goal of this study was to test the potential of ultra‐short echo‐time (UTE) MRI at 1.5, 3.0 and 7.0 T for depiction of trabecular bone structure (of the wrist bones), to evaluate whether T₂* relaxation times of bone water and parametric maps of T₂* of trabecular bone could be obtained at all three field strengths, and to compare the T₂* relaxation times with structural parameters obtained from micro‐computed tomography (micro‐CT) as a reference standard. Ex vivo carpal bones of six wrists were excised en bloc and underwent MRI at 1.5, 3.0 and 7.0 T in a whole‐body MR imager using the head coil. A three‐dimensional radial fat‐suppressed UTE sequence was applied with subsequent acquisitions, with six different echo times T_E of 150, 300, 600, 1200, 3500 and 7000 µs. The T₂* relaxation time and pixel‐wise computed T₂* parametric maps were compared with a micro‐computed‐tomography reference standard providing trabecular bone structural parameters including porosity (defined as the bone‐free fraction within a region of interest), trabecular thickness, trabecular separation, trabecular number and fractal dimension (D_k). T₂* relaxation curves and parametric maps could be computed from datasets acquired at all field strengths. Mean T₂* relaxation times of trabecular bone were 4580 ± 1040 µs at 1.5 T, 2420 ± 560 µs at 3.0 T and 1220 ± 300 µs at 7.0 T, when averaged over all carpal bones. A positive correlation of T₂* with trabecular bone porosity and trabecular separation, and a negative correlation of T₂* relaxation time with trabecular thickness, trabecular number and fractal dimension, was detected (p < 0.01 for all field strengths and micro‐CT parameters). We conclude that UTE MRI may be useful to characterize the structure of trabecular bone, comparable to micro‐CT. Copyright © 2014 John Wiley & Sons, Ltd.     

Structural and Radiological Parameters for the Nondestructive Characterization of Trabecular Bone

Trabecular bone is characterized by compositional and organizational factors. The former include porosity at microlevel and mineralization. The latter refer to the trabecular architecture. Both determine the mechanical properties of the trabecular bone. The aim of this study is to investigate the relationship between the mechanical properties and the local HU value, the bone mineral density, the in vitro histomorphometric properties assessed by means of microcomputed tomography, and the Young's modulus determined by ultrasound measurement. Also the correlation between local HU values based on CT data of the full bone and HU values based on CT data of excised trabecular bone cylinders is investigated. Therefore density and strength related parameters of 22 trabecular bone cylinders retrieved from a fresh cadaver femur were measured by using different techniques. The mean HU value of the excised bone samples is very highly correlated with the pQCT density (R²=0.95) and the CT-based morphometric parameter BV/TV (R²=0.95). The mean HU values, determined from the CT images of the planned and excised bone samples, are less highly correlated (R²=0.75). The Young's modulus E_US determined from the ultrasound measurement is highly correlated with the maximal stress _max (R²=0.88) but not with the mechanically determined Young's modulus E_mech (R²=0.67). The maximal stress _max correlates well with the density parameters (R² varies between 0.76 and 0.86). On the contrary the mechanically determined Young's modulus E_mech does not correlate well with the density parameters (R² varies between 0.52 and 0.56). The absorbed energy E_abs during the deformation is only highly correlated with the maximal stress _max (R²=0.83). The inclusion of structural parameters besides a density related parameter did improve the prediction of the Young's modulus and the maximal stress. In conclusion, it seems that the HU value from clinical CT scanning is a good predictor of the local bone density and volume fraction. A combination of local density and a measure of the structural anisotropy is clearly needed to achieve good predictions of bone mechanics. © 2001 Biomedical Engineering Society. PAC01: 8719Rr, 8759Ls, 4380Ev, 8759Fm, 4335Zc, 8170Cv     

Enhanced bone structural analysis through pQCT image preprocessing

Several factors, including preprocessing of the image, can affect the reliability of pQCT-measured bone traits, such as cortical area and trabecular density. Using repeated scans of four different liquid phantoms and repeated in vivo scans of distal tibiae from 25 subjects, the performance of two novel preprocessing methods, based on the down-sampling of grayscale intensity histogram and the statistical approximation of image data, was compared to 3 × 3 and 5 × 5 median filtering. According to phantom measurements, the signal to noise ratio in the raw pQCT images (XCT 3000) was low (～20 dB) which posed a challenge for preprocessing. Concerning the cortical analysis, the reliability coefficient (R) was 67% for the raw image and increased to 94–97% after preprocessing without apparent preference for any method. Concerning the trabecular density, the R-values were already high (～99%) in the raw images leaving virtually no room for improvement. However, some coarse structural patterns could be seen in the preprocessed images in contrast to a disperse distribution of density levels in the raw image. In conclusion, preprocessing cannot suppress the high noise level to the extent that the analysis of mean trabecular density is essentially improved, whereas preprocessing can enhance cortical bone analysis and also facilitate coarse structural analyses of the trabecular region.     

Electrochemotherapy is effective in the treatment of rat bone metastases

Bone metastases impair general health status, quality of life and survival of patients. Electrochemotherapy (ECT), which combines electroporation (EP) and the administration of anticancer drugs, has been recently introduced into clinical practice for the local treatment of solid tumours. In the present study, the ability of EP with bleomycin (Bleo) to induce MRMT-1 rat breast cancer cell death was investigated in vitro. Then, an in vivo model for bone metastases was set up by the inoculation of MRMT-1 cells in rat proximal tibia. 7 days after tumour induction the animals were treated with Bleo, EP, Bleo followed by EP (ECT), or left untreated. ECT eliminated the tumour in 6 out of 8 (75 %) treated metastases. Radiological evaluation showed that the Honore score in ECT-treated animals was significantly lower when compared with the other groups (p < 0.0005) and not significantly different from healthy controls. Bone morphology in ECT-treated animals, evaluated by histological and microtomographical analyses, showed intact cortical and trabecular bone structure with new bone apposition. Histomorphometric evaluation showed that ECT-treated metastases had significantly higher bone volume, trabecular number, trabecular thickness and bone mineral density compared with those of untreated metastases (respectively p < 0.0005 for BV/TV, Tb.N and BMD; p < 0.05 for Tb.Th) or metastases treated with Bleo (p < 0.05 for BV/TV, Tb.N, p < 0.005 for BMD) or EP (p < 0.005 for BV/TV, Tb.N; p < 0.0005 for BMD). These findings suggest that early ECT treatment of bone metastases is minimally invasive, safe and effective, thus providing pre-clinical evidence for its use in the treatment of human bone metastases.     

Distribution of mesoscale elastic properties and mass density in the human femoral shaft

Abstract

Cortical bone properties are determined by tissue composition and structure at several hierarchical length scales. In this study, the spatial distribution of micro- and mesoscale elastic properties within a human femoral shaft has been investigated. Microscale tissue degree of mineralization (DMB), cortical vascular porosity Ct.Po and the average transverse isotropic stiffness tensor C^Micro of cylindrical-shaped samples (diameter: 4.4?mm, N?=?56) were obtained from cortical regions between 20 and 85% of the total femur length and around the periphery (anterior, medial, posterior and lateral quadrants) by means of synchrotron radiation µCT (SRµCT) and 50-MHz scanning acoustic microscopy (SAM). Within each cylinder, the volumetric bone mineral density (vBMD) and the mesoscale stiffness tensor C^Meso were derived using a numerical homogenization approach. Moreover, microelastic maps of the axial elastic coefficient c₃₃ measured by SAM at distinct cross-sectional locations along the femur were used to construct a 3-D multiscale elastic model of the femoral shaft. Variations of vBMD (6.1%) were much lower than the variations of mesoscale elastic coefficients (11.1–21.3%). The variation of DMB was only a minor predictor for variations of the mesoscale elastic properties (0.05?≤?R^2?≤?0.34). Instead, variations of the mesoscale elastic properties could be explained by variations of cortical porosity and microscale elastic properties. These data were suitable inputs for numerical evaluations and may help to unravel the relations between structure and composition on the elastic function in cortical bone.     

Hydraulic Strengthening Affects the Stiffness and Strength of Cortical Bone

A nonlinear, interstitial fluid flow constitutive model for cortical bone was developed to study the strain-rate dependency of cortical bone apparent modulus (E_a). Nine representative volume element (RVE) structural models of cortical bone spanning an effective pore volume fraction P range of 1–40% were examined. Dynamic loading conditions were used to study the fluid flow contribution or hydraulic strengthening (HS) effect on E_a for each RVE model. The model indicated that there is an upper and lower asymptotic bound of strain-rate (10^{± 3} sec^–1) above or below which there are no further HS effects on E_a. At certain strain-rates (10^–1 to 10⁰ sec^–1) variations in cortical bone porosity had little or no influence on E_a. At lower and higher frequencies, the loss tangent, hence the magnitude of viscoelastic effects is greater. For strain-rates less than 10^–1 sec^–1, lower porosity RVE models were always stiffer than higher porosity RVE models. A generalized power law model is proposed to account for the fact that HS in cortical bone exhibits an upper and lower asymptotic bound and is bi-modal in terms of strain-rate.