Interindividual and intraspecimen variability of 3-D bone microarchitectural parameters in iliac crest biopsies imaged by conventional micro-computed tomography

Bone microarchitecture of the iliac bone is used to characterize the properties of bone tissue in osteoporosis, particularly in pharmacological studies. Trabecular bone is known to be heterogeneous media. For a few years, the analysis of three-dimensional (3-D) bone microarchitecture has been based on micro-computed tomography (micro-CT). To assess the interindividual variability (inter-indVar) and the intrasample variability (intra-sampVar) of iliac crest biopsies, we used a Bordier needle trephine in 35 postmenopausal female cadavers (mean age, 74.4 +/- 10.4 years). Finally, we had at our disposal 32 individual iliac crests to assess the inter-indVar and 21 oriented specimens to assess the intra-sampVar. All the samples were chemically defatted, and the images were performed with a desktop micro-CT with a voxel size of 10.77 mum. We measured trabecular bone parameters: bone volume/tissue volume (BV/TV %), trabecular thickness and spacing (Tb. Th*, Tb.Sp* mum), bone surface/bone volume (BS/BV, 1/mm), the trabecular number (Tb.N, 1/mm), structure model index (SMI), trabecular pattern factor (Tb.Pf), and degree of anisotropy (DA). We also measured cortical bone parameters: cortical thickness (Cort.Th), porosity (PoV/TV), and pore diameter (Po.Dm). For the inter-indVar, we analyzed a fixed volume of interest corresponding to 119.8 mm(3) centered on each iliac crest. To assess the intra-sampVar, we divided the whole trabecular volume into three equal height parts (external, middle, internal). BV/TV, Tb.N, and PoV/TV were negatively correlated with age and Tb.Sp* and SMI were positively correlated. The mean difference of absolute individual variations in percentage with the middle area used as a reference, comparatively to external and internal areas, ranged from 6.6% (Tb.Sp*) to 27.8% (BV/TV), except Tb.Pf, which showed large variability. There was no difference between external and internal areas, with a tendency for lower values of BV/TV, Tb.Th*, and Tb.N in the middle of the iliac crest and higher values of Tb.Sp* and BS/BV. The evaluation of bone microarchitecture of iliac crest samples on micro-CT images is reliable. The heterogeneity of bone inside the iliac crest is noticeable as leading to analyzing the largest possible quantity of bone, with standardized location, according to cortex but without any assumption of orientation.     

骨碎补总黄酮对去卵巢大鼠下颌骨显微结构及最大载荷的影响

目的应用Micro-CT和骨生物力学技术,探讨骨碎补总黄酮对去卵巢大鼠的下颌骨显微结构及最大载荷的影响。方法40只3月龄雌性SD大鼠,随机分为5组:假手术组(sham operation group,Sham)、去卵巢模型组(ovariectomized group,OVX)、骨碎补总黄酮高剂量组(high-dose drynaria total flavonoids group,GB-H)、骨碎补总黄酮低剂量组(low-dose drynaria total flavonoids group,GB-L)和戊酸雌二醇组(Estradiol Valerate group,EV),建模成功后连续给药12 w。实验结束后,取下颌骨进行显微CT扫描及三维重建,然后进行最大载荷测量。结果与Sham组相比,OVX组大鼠下颌骨微结构:骨密度、相对骨体积、骨小梁厚度、骨小梁数目明显减小(P0.05),骨表面积体积比、骨小梁间隙明显增高(P0.05);下颌骨的最大载荷明显减少(P0.05)。与OVX组相比,EV组大鼠下颌骨微结构获得良好修复,最大载荷也明显修复。骨碎补总黄酮低剂量组相对骨体积、骨小梁数目较OVX组显著升高(P0.05),骨小梁间隙显著减小(P0.05)。骨碎补总黄酮高剂量组疗效优于低剂量组,大鼠下颌骨的相对骨体积、骨表面积体积比、骨小梁间隙、骨小梁数目以及下颌骨骨密度均得到一定程度修复,下颌骨最大载荷也较OVX组显著增加(P0.05)。结论骨碎补总黄酮能够修复去卵巢大鼠下颌骨微结构,提高下颌骨骨密度和最大载荷,这将可能为颌骨骨质疏松的防治提供一种新的途径。     

Predicting human vertebral bone strength by vertebral static histomorphometry

The study investigates the relationship between static histomorphometry and bone strength of human lumbar vertebral bone. The ability of vertebral histomorphometry to predict vertebral bone strength was compared with that of vertebral densitometry, and also with histomorphometry and bone strength of iliac crest bone biopsies. The material comprised matched sets of second lumbar vertebrae, third lumbar vertebrae, and two iliac crest bone biopsies from each of 21 women (19--96 years) and 24 men (23--95 years). One of the iliac crest biopsies and 9-mm-thick mediolateral slices of half of each of the entire vertebral bodies (L-2) were used for histomorphometry. The other iliac crest biopsies and the L-3 were destructively tested by compression. High correlation was found between BV/TV or Tb.Sp and vertebral bone strength (absolute value of r = 0.86 in both cases). Addition of Tb.Th significantly improved the correlation between BV/TV and bone strength, and the addition of bone space star volume significantly improved the correlation between Tb.Sp and bone strength (from absolute value of r = 0.86 to absolute value of r = 0.89 in both cases). Bone structure (connectivity density) was not capable of improving the prediction of bone strength of the vertebral body. The correlations between BV/TV of L-2 and bone strength of L-3 were comparable with the correlation obtained by quantitative computed tomography (QCT), peripheral QCT (pQCT), and dual-energy X-ray absorptrometry (DEXA) of L-3 and bone strength of L-3. The iliac crest was found to have low predictive power of vertebral bone strength (iliac BV/TV: r = 0.62; iliac bone strength: r = 0.67). No gender-related differences were found in any of the relationships. It was shown that trabecular bone volume BV/TV and mean trabecular plate separation Tb.Sp are good predictors of vertebral bone strength. The ability of histomorphometry to predict vertebral bone strength was comparable to that of densitometry. Bone structure assessed by connectivity density did not improve the correlation between static histomorphometric measures and vertebral bone strength. No gender-related differences were found in any of the relationships. Neither static histomorphometry nor biomechanical testing of iliac crest bone biopsies is a good predictor of vertebral bone strength.     

Predictive value of bone mineral density and morphology determined by peripheral quantitative computed tomography for cancellous bone strength of the proximal femur

Peripheral quantitative computed tomography (pQCT) is an established diagnostic method for assessment of bone mineral density in the diagnosis of osteoporosis. However, the capacity of structural parameters of cancellous bone measured by high-resolution computed tomography remains to be explored. In 33 patients, bone mineral density (BMD) of the proximal femur was measured in vitro by pQCT using cylindrical biopsies from the intertrochanteric region harvested before the implantation of an artificial hip joint. By digital image analysis of CT scans, parameters derived from histomorphometry describing the microarchitecture of cancellous bone were measured. The biopsies were also loaded to failure by an uniaxial compression test to determine the biomechanical parameters, Young's modulus, strength, and maximum energy absorption (E(max)). Strong correlations were found for BMD vs. mechanical parameters (r = 0.73 for Young's modulus, r = 0.82 for strength, and r = 0.79 for E(max); p < 0.001, n = 29). The morphological parameters, bone volume per trabecular volume (BV/TV), apparent trabecular thickness (app.Tb.Th), apparent trabecular separation (app.Tb.Sp), and trabecular number (Tb.N), correlated significantly with all mechanical parameters. The combination of morphological parameters with BMD in a multivariate regression model led to an overall, but only moderate, increase in R(2) in all cases. Our data confirm the high predictive value of BMD for the mechanical competence of cancellous bone of the intertrochanteric region. However, quantification of cancellous bone structure by image analysis of CT scans may provide additional qualitative information for the analysis of bone strength.     

曲古抑菌素A促进去卵巢大鼠钛植入物骨整合

目的 探讨TSA对去卵巢大鼠TI骨整合的影响。方法 将30只健康3月龄雌性SD大鼠随机分为Sham组（n=5）和OVX组（n=25）。正常饲养3个月后,两组各选取5只大鼠处死,取股骨远端样本行Micro-CT和HE染色以鉴定是否成功建立骨质疏松模型。随后在OVX组剩余大鼠双侧股骨干骺端植入直径1.5 mm TI,并将其分为2组：Control组（n=10）和TSA组（n=10）。连续给药4周。给药结束后处死全部大鼠并取股骨样本行Micro-CT扫描、HE染色以及Masson染色,ELISA法检测,拔钉实验。结果 与Sham组对比,Micro-CT显示OVX组BMD、BV/TV、Tb.Th、Tb.N降低（P<0.05）,而Tb.Sp、SMI升高（P<0.05）,HE染色显示OVX组骨小梁数量明显降低。与Control组对比,Micro-CT显示TSA组BMD、BV/TV、Tb.Th、Tb.N 、Conn.D均升高（P<0.05）,而Tb.Sp、SMI降低（P<0.05）,HE染色、Masson染色显示TSA组骨小梁数量、新生骨数量均升高,ELISA法检测结果显示TSA组OCN、BMP2均升高,拔钉实验显示TSA组TI轴向拔出力增大。结论 TSA通过上调OCN、BMP2等成骨相关蛋白,促进骨小梁形成和新骨形成,进而改善去卵巢大鼠TI骨整合。     

Relationships between bone structure in the iliac crest and bone structure and strength in the lumbar spine

The purpose of this study was to examine the relationship between histomorphometric variables of cancellous bone structure and ultimate compressive strength (UCS) in the second lumbar vertebra (L2) and to determine whether structural variables in the iliac crest are predictive of the same variables and of UCS in L2. At autopsy, 7.5 mm diameter cores were removed from the iliac crest and from L2 of 29 subjects who had died suddenly without bone disease. Cancellous bone volume (BV/TV, %) was significantly lower in L2 than in iliac crest due to lower trabecular number (Tb.N, per mm) and thickness (Tb.Th, µm). There were significant correlations between iliac crest and L2 for BV/TV, Tb.N and trabecular separation (Tb.Sp, µm), but not for Tb.Th. BV/TV was negatively correlated, and Tb.Sp was positively correlated with age at both sites. Tb.Th was not significantly correlated with age in the iliac crest, but a significant negative correlation was observed in L2. The UCS of vertebral cores was negatively correlated with age. BV/TV and Tb.Th in L2 were positively correlated with UCS in L2. Cortical width and BV/TV in iliac crest were positively correlated with UCS in L2. We conclude that: (1) cancellous bone volume in the iliac crest is higher than in the lumbar spine due to thicker, more closely spaced trabecular plates, (2) the changes in structural variables with age are generally similar in the iliac crest and lumbar vertebra, but trabecular thinning with age is more evident in the spine than in the ilium, and (3) the compressive strength of cancellous bone in the lumbar spine is correlated with histomorphometric variables of bone structure, as measured both in the lumbar spine and in the iliac crest.     

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.     

Role of trabecular microarchitecture and its heterogeneity parameters in the mechanical behavior of ex vivo human L3 vertebrae

Low bone mineral density (BMD) is a strong risk factor for vertebral fracture risk in osteoporosis. However, many fractures occur in people with moderately decreased or normal BMD. Our aim was to assess the contributions of trabecular microarchitecture and its heterogeneity to the mechanical behavior of human lumbar vertebrae. Twenty‐one human L₃ vertebrae were analyzed for BMD by dual‐energy X‐ray absorptiometry (DXA) and microarchitecture by high‐resolution peripheral quantitative computed tomography (HR‐pQCT) and then tested in axial compression. Microarchitecture heterogeneity was assessed using two vertically oriented virtual biopsies—one anterior (Ant) and one posterior (Post)—each divided into three zones (superior, middle, and inferior) and using the whole vertebral trabecular volume for the intraindividual distribution of trabecular separation (Tb.Sp*SD). Heterogeneity parameters were defined as (1) ratios of anterior to posterior microarchitectural parameters and (2) the coefficient of variation of microarchitectural parameters from the superior, middle, and inferior zones. BMD alone explained up to 44% of the variability in vertebral mechanical behavior, bone volume fraction (BV/TV) up to 53%, and trabecular architecture up to 66%. Importantly, bone mass (BMD or BV/TV) in combination with microarchitecture and its heterogeneity improved the prediction of vertebral mechanical behavior, together explaining up to 86% of the variability in vertebral failure load. In conclusion, our data indicate that regional variation of microarchitecture assessment expressed by heterogeneity parameters may enhance prediction of vertebral fracture risk. © 2010 American Society for Bone and Mineral Research.     

The ability of three-dimensional structural indices to reflect mechanical aspects of trabecular bone.

Bone mineral density (BMD) and bone microarchitecture are important determinants for the mechanical properties of cancellous bone. Although BMD alone is a good predictor of average mechanical properties of cancellous bone, there remains unexplained variation in mechanical properties that might be due to missing information regarding bone microarchitecture. Recent developments in three-dimensional (3D) structural analysis have provided possibilities for measuring a variety of structural indices to characterize bone microarchitecture. The objectives of this study were to calculate structural indices and elastic constants of human cancellous bone from different skeletal sites and to investigate the predictive value of different 3D structural indices for the elastic properties of bone. A total of 237 cancellous bone samples taken from the iliac crest, lumbar spine, femoral head, and calcaneus were imaged with a 3D microcomputed tomography (microCT) system. The segmented 3D images were used to calculate BV/TV, BS/TV, Tb.Th, Tb.Sp, Tb.N, and MII ratio and for microstructural finite-element (microFE) analysis to calculate Young's moduli, shear moduli, and Poisson's ratios. A subgroup of "critical" specimens within each site was selected to represent specimens that could not be identified as osteoporotic or normal on the basis of BMD measurement alone. For these "critical" specimens, structural indices and elastic constants were correlated by means of linear multivariate regression analysis. It was found that the elastic constants clearly correlated better when one of the 3D structural indices was included as independent variable than when BV/TV was the only independent variable. Each of the examined structural indices could improve the correlation: the R2 values were maximally increased from 53% (BV/TV alone) to 82% (BV/TV and MIL ratio). The most effective indices, however, were not the same for the different skeletal sites. Even better correlations were found when more than one of the 3D structural indices were included as independent variables: the R2 values were maximally increased from 53% (BV/TV alone) to 92% (BV/TV, Tb.Sp, and MIL ratio). The prediction of elastic constants for cancellous bone samples is clearly improved when BV/TV is supplemented with 3D structural indices. These results suggest that the determination of mechanical properties of bone and the diagnosis of osteoporosis can be improved if, in addition to BMD, the 3D bone microarchitecture is assessed in vivo.     

Side-to-side and within-side variability of 3D bone microarchitecture by conventional micro-computed tomography of paired iliac crest biopsies

Bone microarchitecture in osteoporosis can be characterized by examining iliac bone biopsies and treatment effects assessed by comparing a baseline biopsy from one side to a posttreatment biopsy from the other side, a method that assumes limited side-to-side variability. New techniques based on micro-computed tomography (microCT) provide information on the three-dimensional (3D) microarchitecture of bone. We used microCT to measure side-to-side and within-side variability of 3D microarchitectural parameters of trabecular and cortical bone in paired iliac-crest biopsies, one from each side. A Bordier needle trephine was used to collect biopsies from 30 postmenopausal female cadavers (mean age, 73.7+/-10.7 years; range, 55-96 years). Biopsies were chemically defatted then imaged using a desktop microCT scanner (voxel size, 10.77 microm). Parameters measured in trabecular bone consisted of bone volume/tissue volume (BV/TV, %), direct trabecular thickness and trabecular spacing (Tb.Th and Tb.Sp, microm) using the sphere method, bone surface/bone volume (BS/BV, mm(-1)), trabecular number (Tb.N, mm(-1)), structure model index (SMI), trabecular pattern factor (Tb.Pf), and degree of anisotropy (DA). In cortical bone, we measured cortical thickness (Cort.Th), porosity (Cort.Porosity), and pore diameter (Po.Dm). For trabecular bone parameters, reproducibility as assessed from two microCT acquisitions ranged from 4.1% to 6.9%. To assess side-to-side variability, we matched the volumes of interest selected in the right and left iliac crests. The mean difference in absolute individual percent variation (mAbsDelta(ind)) between the two sides ranged from 10.8% to 14.8% for all trabecular parameters except Tb.Pf (74%) and SMI (84%). In cortical bone, mAbsDelta(ind) were 11.6% for Po.Dm, 15.1% for Cort.Porosity, and 27.6% for Cort.Th. To assess within-side variability, we divided the trabecular iliac crest volume into three equal parts, one adjacent to each cortex and one in the middle. Values of mAbsDelta(ind) versus the middle part were ranging from 7.6% for Tb.Sp to 26.2% for BV/TV. Thus, within-side variability was similar in magnitude to side-to-side variability. The considerable differences in robustness across trabecular parameters indicate a need for selecting the most stable parameters, most notably for longitudinal studies of small numbers of patients. Acquisition by microCT and image analysis must comply with stringent quality criteria, especially the distance from the cortices must be standardized.     

Gender differences in trabecular bone architecture of the distal radius assessed with magnetic resonance imaging and implications for mechanical competence

High-resolution magnetic resonance imaging (hrMRI) has recently made it possible to evaluate trabecular bone structure in vivo. Despite obvious gender differences in fracture incidence at the distal radius, little is known about gender differences in trabecular bone microarchitecture and its relationship to the structural strength of the forearm. The aim of this study was to determine trabecular bone structure in the distal radius of elderly women and men and its correlation with failure loads of the distal radius as determined in a fall configuration. Specifically, we tested the hypotheses that structural indices differ between women and men and that they offer information that is independent from BMD for predicting structural strength. Intact right arms were obtained from 73 formalin-fixed cadavers (age 80±11 years, 43 women, 30 men). Trabecular structural indices (apparent bone volume fraction [app. BV/TV], trabecular number [app. Tb.N], trabecular separation [app. Tb.Sp], trabecular thickness [app. Tb.Th] and fractal dimension [Frac.Dim]) were assessed in the distal metaphysis, using hrMRI with 156 µm in-plane resolution and proprietary digital image analysis, while BMD was measured with dual X-ray absorptiometry (DXA). Women displayed significantly lower BMD (–29.8%, p <0.001), app. BV/TV (–8.2%, p <0.05) and app. Tb.Th (–10.2%, p <0.001) than men, whereas app. Tb.N, app. Tb.Sp. and fractal dimension did not differ significantly. Structural parameters differed between normal and osteopenic women (BV/TV: –11%, p <0.01; Tb.Th: –8%, p <0.001) and between normal and osteoporotic women BV/TV: –21%, p <0.001; Tb.Th: –16%, p <0.001). App. BV/TV, app. Tb.Th and fractal dimension provided information independent from BMD in the prediction of radial failure loads in multiple regression models. These findings imply that it should be of clinical interest to monitor both bone mass and trabecular microstructure for predicting osteoporotic fracture risk.     

PM2.5对去势后雌性SD大鼠骨微结构micro-CT的影响

目的探讨不同浓度的PM_(2.5)暴露对去势SD雌性大鼠骨微结构的影响。方法用不同浓度(35、70、150μg/m3)的PM_(2.5)对SD大鼠进行气道滴注,随机分为低剂量组、中剂量组和高剂量组,滴注后5个月末行去势手术;滴注后9个月末取股骨、胫骨、腰椎,运用显微计算机断层扫描术(micro-CT)分别检测三者骨微结构。结果与对照组相比,PM_(2.5)暴露组胫骨、股骨、腰椎的骨小梁骨密度(Tb.BMD)减小、骨体积分数(BV/TV)减小、结构模型指数(SMI)增大、骨小梁厚度(Tb.Th)减小、骨小梁数量(Tb.N)减少、骨小梁分离度(Tb.Sp)增加; PM_(2.5)暴露组中,胫骨骨小梁的BV/TV、Tb.Th、Tb.N、Tb.Sp指标改变与对照组比较差异有统计学意义(P0.05),股骨骨小梁的Tb.BMD、BV/TV、SMI、Tb.N、Tb.Sp指标改变与对照组比较差异有统计学意义(P0.05),腰椎骨小梁的SMI、Tb.Th、Tb.N、Tb.Sp指标改变与对照组比较差异有统计学意义(P0.05)。从micro-CT三维重建图结果看,与对照组比较,PM_(2.5)暴露组胫骨骨髓腔内明显空虚,骨小梁缺如;股骨Ward三角区骨小梁数量稀疏、间隙变大;腰椎骨小梁结构的完整性被破坏,杆状结构增多。结论表明PM_(2.5)暴露可使去势后雌性SD大鼠胫骨、股骨、腰椎骨小梁结构遭到破坏,数量减少,由片状结构转为杆状结构,由此可见PM_(2.5)暴露可加重绝经后骨量丢失。     

Puerariae radix prevents bone loss in ovariectomized mice

Puerariae radix (PR), the root of Pueraria labata (Willd.) Ohwi, a wild creeper leguminous plant, is one of the earliest and most important crude herbs used in Chinese medicine for various medicinal purposes. PR contains a high amount of isoflavonoids such as daidzein and genistein, which are known to prevent bone loss induced by estrogen deficiency. We have demonstrated that soybean isoflavones prevent bone loss in an osteoporotic animal model. To examine the possible role of PR in bone metabolism, female mice were ovariectomized (OVX), and some OVX mice were fed a diet containing low, middle, and high doses (5%, 10%, and 20% of diet, respectively) of PR for 4 weeks. In OVX mice, the uterine weight declined, and intake of PR at any dose did not affect uterine weight. The total femoral bone mineral density (BMD) was significantly reduced by OVX, and the decrease in BMD caused by OVX was significantly inhibited by intake of the diet with the low dose of PR and completely prevented by the middle dose of PR. Histological analysis of the femoral metaphysis showed that intake of the diet with the middle dose of PR completely prevented decrease in trabecular bone volume (BV/TV) and trabecular thickness (Tb.Th) and restored the increase in trabecular separation (Tb.Sp) in OVX mice. In contrast, intake of the diet with the high dose of PR further increased BV/TV and Tb.Th and decreased Tb.Sp in OVX mice compared with that in the sham-operated mice. These results suggest that PR may represent a potential alternative medicine for hormone replacement therapy (HRT) in the prevention of osteoporosis in postmenopausal women.     

Patient-specific microarchitecture of vertebral cancellous bone: a peripheral quantitative computed tomographic and histological study

This study directly compares peripheral quantitative computed tomography (pQCT) and histology for the assessment of 11 morphological parameters. Sixty-eight cylindrical cancellous bone samples were cored from the thoracic (T-9) thoracolumbar (T-12 or L-1), and lumbar (L-4) vertebral bodies of nine autopsy subjects (aged 44–88 years). Four transverse slices were acquired by pQCT from the bottom to the top of each cylinder. Slice thickness was 300 μm and pixel size was 70 × 70 μm. Thin sections (5 μm) were obtained at the same location in the samples, stained with Von Kossa, and photographed. Classical morphological parameters and strut analysis parameters were measured on all images (272 pQCT and 272 matched histological sections). Because of the partial volume effect and specific thresholding procedure, pQCT overestimated the absolute value of the bone volume fraction (BV/TV) and trabecular thickness (Tb.Th) by a factor 2. The trabecular number (Tb.N), trabecular spacing (Tb.Sp), and total strut length (TSL) were correctly estimated. However, the direct correlation between pQCT and histology was excellent (r² > 0.85, p < 0.001) for BV/TV, Tb.N, Tb.Sp, TSL, and star surface. For Tb.Th, number of nodes, and number of free ends, the correlation was also good (r² > 0.6, p < 0.001). Using a random regression model, we also explored the ability of these parameters to add structural information to the readily available BV/TV or apparent density. The model identified significant (p < 0.001) differences between subjects. For a given BV/TV, some patients had more trabeculae (Tb.N) that were thinner (Tb.Th) and more disconnected (higher free ends and star). This was observed for both histology and pQCT morphometrical data. Our analysis demonstrates the capacity of both histology and pQCT to detect subjects with specific structural patterns in vertebral cancellous bone.     

Goats as an osteopenic animal model.

A large osteopenic animal model that resembles human osteoporotic changes is essential for osteoporosis research. This study aimed at establishing a large osteopenic animal model in goats. Twenty-five Chinese mountain goats were used in which they were either ovariectomized (OVX) and fed with a low-calcium diet (n = 16) or sham-operated (SHAM; n = 9). Monthly photodensitometric analysis on proximal tibial metaphysis and calcaneus was performed. Two iliac crest biopsy specimens obtained before and 6 months after OVX were used for bone mineral density (BMD) measurement with peripheral quantitative computed tomography (pQCT). Lumbar vertebrae (L2 and L7), humeral heads, and calcanei were collected for BMD measurement after euthanasia. The humeral heads and calcanei were used in biomechanical indentation test. BMD measurement showed a significant 25.0% (p = 0.006) decrease in BMD of the iliac crest biopsy specimens 6 months after OVX. It also was statistically significant when compared with the SHAM (p = 0.028). BMD at L2, L7, calcaneus, and humeral head reduced by 24-33% (p ranged from 0.001 to 0.011) when compared with the SHAM. Photodensitometry showed a continuous decrease in bone density after OVX. There were significant decreases of 18.9% in proximal tibial metaphysis (p = 0.003) and 21.8% in calcaneus (p = 0.023) in the OVX group 6 months postoperatively. Indentation test on the humeral head and calcaneus showed a significant decrease 52% (p = 0.006) and 54% (p = 0.001), respectively, in energy required for displacement of 3 mm in the OVX group compared with the SHAM group. The decreases correlated significantly to the decrease in BMD of the corresponding specimens (r2 = 0.439 and 0.581; p < 0.001 for both). In conclusion, this study showed that OVX plus a low-calcium diet could induce significant osteopenia and deterioration of mechanical properties of the cancellous bone in goats.     

Measuring Apparent Trabecular Structure With pQCT: A Comparison With HR-pQCT

We evaluated how comparable peripheral quantitative computed tomography (pQCT) measurements of cortical thickness, density, and apparent trabecular structure at the ultradistal tibia were with those measured with high-resolution pQCT (HR-pQCT). We also examined whether the accuracy of the pQCT-based trabecular and cortical measurements improved with reductions in slice thickness from the standard 2.2 mm to 1.1 and 0.6 mm. We immersed 15 dry tibia specimens in saline in a sealed cylinder and scanned 22.5 mm from the distal tibia plateau using pQCT and HR-pQCT. pQCT underestimated cortical thickness by Stratec (CTh_Stratec) and trabecular spacing (Tb.Sp) by 21.4% and 72.9%, whereas bone volume to total volume (BV/TV) and cortical density (CDen) were overestimated by 265.8% and 13.1%, respectively. Measurements of trabecular volumetric bone mineral density, trabecular area, total area, cortical thickness by custom software were comparable, but for CTh_Stratec, Tb.Sp, BV/TV, and CDen, the differences between imaging devices varied with magnitude of the estimate. We recommend that researchers or clinicians interested in using pQCT to measure apparent trabecular structure or cortical thickness at the epiphyses, or in comparing findings from different devices, be aware of the differences between HR-pQCT and pQCT.     

High‐resolution peripheral quantitative computed tomography can assess microstructural and mechanical properties of human distal tibial bone

High‐resolution peripheral quantitative computed tomography (HR‐pQCT) is a newly developed in vivo clinical imaging modality. It can assess the 3D microstructure of cortical and trabecular bone at the distal radius and tibia and is suitable as an input for microstructural finite element (µFE) analysis to evaluate bone's mechanical competence. In order for microstructural and image‐based µFE analyses to become standard clinical tools, validation with a current gold standard, namely, high‐resolution micro‐computed tomography (µCT), is required. Microstructural measurements of 19 human cadaveric distal tibiae were performed for the registered HR‐pQCT and µCT images, respectively. Next, whole bone stiffness, trabecular bone stiffness, and elastic moduli of cubic subvolumes of trabecular bone in both HR‐pQCT and µCT images were determined by µFE analysis. The standard HR‐pQCT patient protocol measurements, derived bone volume fraction (BV/TV^d), trabecular number (Tb.N*), trabecular thickness (Tb.Th), trabecular spacing (Tb.Sp), and cortical thickness (Ct.Th), as well as the voxel‐based direct measurements, BV/TV, Tb.N*, Tb.Th*, Tb.Sp*, Ct.Th, bone surface‐to‐volume ratio (BS/BV), structure model index (SMI), and connectivity density (Conn.D), correlated well with their respective gold standards, and both contributed to µFE‐predicted mechanical properties in either single or multiple linear regressions. The mechanical measurements, although overestimated by HR‐pQCT, correlated highly with their gold standards. Moreover, elastic moduli of cubic subvolumes of trabecular bone predicted whole bone or trabecular bone stiffness in distal tibia. We conclude that microstructural measurements and mechanical parameters of distal tibia can be efficiently derived from HR‐pQCT images and provide additional information regarding bone fragility. © 2010 American Society for Bone and Mineral Research     

Microarchitecture of the Radial Head and Its Changes in Aging

Fractures of the radial head are common; however, it remains to be determined whether the radial head has to be considered as a typical location for fractures associated with osteoporosis. To investigate whether the human radial head shows structural changes during aging, we analyzed 30 left and 30 right human radial heads taken from 30 individuals. The specimens taken from the left side were analyzed by peripheral quantitative computed tomography (pQCT) and micro-CT. The specimens taken from the right elbow joint were analyzed by radiography and histomorphometry. In these specimens pQCT revealed a significant decrease of total and cortical bone mineral density (BMD_to BMD_co) with aging, regardless of sex. Histomorphometry revealed a significant reduction of cortical thickness (Ct.Th), bone volume per tissue volume (BV/TV), and trabecular thickness (Tb.Th) in male and female specimens. In this context, mean BV/TV and mean trabecular number (Tb.N) values were significantly lower and, accordingly, mean trabecular separation (Tb.Sp) was significantly higher in female samples. The presented study demonstrates that the radial head is a skeletal site where different age- and sex-related changes of the bone structure become manifest. These microarchitectural changes might contribute to the pathogenesis of radial head fractures, especially in aged female patients where trabecular parameters (BMD_tr and Tb.Sp) change significantly for the worse compared to male patients.     

Trabecular architecture in iliac crest bone biopsies: infra-individual variability in structural parameters and changes with age

A histomorphometric study was conducted on bilateral iliac crest samples obtained at autopsy from 27 subjects who had died suddenly. Six parameters related to cancellous bone structure were measured: bone volume (BV/TV), surface density (BS/TV), surface/volume ratio (BS/BV), trabecular thickness (Tb.Th.), trabecular number (Tb.N), and trabecular separation (Tb.Sp). There were no significant differences between right and left sides in the mean values for each parameter. However, when subjects were considered individually, there was a substantial difference in the majority of cases for all parameters. The intra-individual variation (IIV) was calculated for each subject as the percentage deviation from the mean for the two sides. There was a wide range in IIV (0.05-30.27%) with a mean value of approximately 11.5% for each parameter. In males the mean IIV ranged from 9 to 11% and from 14 to 16% in females. The IIV in BV/TV was positively correlated with age. Data generated on a subsample of 15 males were used to predict patient group sizes required to detect minimum significant differences in studies involving repeat biopsies. Sample sizes of 32, 16, and 8 patients would be required for relative increments in BV/TV of 29, 36, and 46%, respectively, to be statistically significant. Tb.Sp increased significantly with age but there was no significant change in Tb.Th. This supports the view that bone loss with aging occurs primarily through a mechanism involving complete disappearance of individual trabecular plates.