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.     

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.     

Trabecular shear stress amplification and variability in human vertebral cancellous bone: relationship with age, gender, spine level and trabecular architecture

Trabecular shear stress magnitude and variability have been implicated in damage formation and reduced bone strength associated with bone loss for human vertebral bone. This study addresses the issue of whether these parameters change with age, gender or anatomical location, and if so whether this is independent of bone mass. Additionally, 3D-stereology-based architectural parameters were examined in order to establish the relationship between stress distribution parameters and trabecular architecture. Eighty cancellous bone specimens were cored from the anterior region of thoracic 12 and donor-matched lumbar 1 vertebrae from a randomly selected population of 40 cadavers. The specimens were scanned at 21-microm voxel size using microcomputed tomography (microCT) and reconstructed at 50microm. Bone volume fraction (BV/TV), trabecular number (Tb.N), trabecular thickness (Tb.Th), trabecular separation (Tb.Sp), bone surface-to-volume ratio (BS/BV), degree of anisotropy (MIL1/MIL3), and connectivity density (-#Euler/Vol) were calculated directly from micro-CT images. Large-scale finite element models were constructed and superoinferior compressive loading was simulated. Apparent cancellous modulus (EFEM) was calculated. The average trabecular von Mises stress generated per uniaxial apparent stress (sigma (-)VM / sigmaapp) and coefficient of variation of trabecular von Mises stresses (COV) were calculated as measures of the magnitude and variability of shear stresses in the trabeculae. Mixed-models and regression were used for analysis. sigma(-)VM / sigmaapp and COV were not different between genders and vertebrae. Both sigma(-)VM / sigmaapp and COV increased with age accompanied by a decrease in BV/TV. Strong relationship of sigma(-)VM / sigmaapp with BV/TV was found whereas COV was strongly related to EFEM/(BV/TV). The results from T12 and L1 were not different and highly correlated with each other. The relationship of sigma(-)VM / sigmaapp with COV was observed to be different between males and females. This difference could not be explained by architectural parameters considered in this study. Our results support the relevance of trabecular shear stress amplification and variability in age-related vertebral bone fragility. The relationships found are expected to help understand the micro-mechanisms by which cancellous bone mass and mechanical properties are modulated through a collection of local stress parameters.     

Preserved three-dimensional cancellous bone structure in mild primary hyperparathyroidism

By conventional 2-dimensional, histomorphometric analysis, we and others have previously shown that cancellous bone architecture is preserved in mild primary hyperparathyroidism (PHPT). We have now extended these observations to a 3-dimensional analysis using microcomputed tomography (microCT). Iliac crest bone biopsies were analyzed from the following subjects with PHPT: 22 postmenopausal women; 7 premenopausal women; similar numbers of normal pre- and postmenopausal women served as controls. Fifteen men with PHPT were also studied. Postmenopausal women with PHPT demonstrated features of preserved cancellous bone as shown by smaller age-related declines in cancellous bone volume (BV/TV) and connectivity density (Conn.D) and no change in bone surface/total volume (BS/TV) as compared to normal women. In postmenopausal women with PHPT, cancellous bone volume (BV/TV), bone surface/total volume, and connectivity density (Conn.D) were all higher, and trabecular separation (Tb.Sp) was lower than in postmenopausal controls. In sharp contrast to the findings in normal women, no structural variables in PHPT women were correlated with age. Also of note, there was no difference in any 3-dimensional index between women and men with PHPT. We conclude that three-dimensional, cancellous bone microarchitecture is preserved in patients with mild primary hyperparathyroidism.     

Long-term effects of withdrawal of bisphosphonate incadronate disodium (YM175) on bone mineral density, mass, structure, and turnover in the lumbar vertebrae of ovariectomized rats.

This study was designed to evaluate the long-term effects of incadronate disodium (YM175) after its withdrawal on cancellous bone mass in ovariectomized (OVX) rats. Thirteen-week-old female SD rats were randomized into four groups: sham-operated, OVX, low-YM, and high-YM (0.01 mg/kg or 0.1 mg/kg subcutaneously [sc], three times a week after OVX) groups. After 4 weeks of treatment with vehicle or YM175, rats from each group were killed at time points of 0 (baseline), 3, 6, 9, and 12 months after withdrawal of the agent. Bone mineral density (BMD) of the lumbar vertebrae was measured by dual-energy X-ray absorptiometry (DXA). Bone volume (BV/TV), trabecular number and trabecular separation (Tb.N and Tb.Sp), eroded surface (ES/BS), osteoclast number and osteoclast surface (N.Oc/BS and Oc.S/BS), osteoid surface (OS/BS), and bone formation rate (BFR/BS) were measured as histomorphometric parameters of the fifth lumbar vertebra. BMD, BV/TV, Tb.N, and Tb.Sp in YM175-treated groups were maintained at the same level as in the sham group until 12 months after withdrawal in the high-YM group and until 3 months after withdrawal in the low-YM group. YM175 decreased both bone formative and resorptive parameters in histomorphometry. Serum bone-specific alkaline phosphatase (ALP) and urinary deoxypyridinoline at both doses of YM175 also showed a suppressive effect of this agent on bone turnover. These results indicate that YM175, after withdrawal, still maintains bone volume dose dependently by depressing bone resorption and formation in OVX rats. Intermittent YM175 treatment with a long interval may be sufficient to maintain the bone volume and structure in OVX rats.     

通过Micro-CT评价瘦素受体缺乏的2型糖尿病小鼠四肢骨的骨代谢变化

目的探讨瘦素受体(leptin receptor,Lepr)缺乏的2型糖尿病小鼠的骨骼表型,为2型糖尿病((T2DM)合并骨质疏松(OP)的防治提供一个新的靶点。方法获取20只14周龄雄性db/db小鼠(瘦素受体缺乏小鼠)和野生型小鼠(C57BL小鼠)的胫骨(各10只),通过Micro-CT检测比较两者骨小梁相对体积(BV/TV)、骨表面积组织体积比值(BS/TV)、骨小梁厚度(Tb.Th)、骨小梁数量(Tb.N)、骨小梁分离度(Tb.Sp)、骨结构模型指数(SMI)、骨皮质厚度(Ct.Th)、骨皮质面积(Ct.Ar)等骨微结构参数的差异。结果与野生型小鼠相比,14周龄的db/db小鼠的胫骨骨小梁相对体积(BV/TV)、骨小梁厚度(Tb.Th)、骨小梁数量(Tb.N)明显减小,小梁骨间距(Tb.Sp)相应增加,皮质骨厚度(Ct.Th)、横截面积(Ct.Ar)减小,两者比较差异均有显著统计学意义(P0.05);其结构模式指数(structure model index,SMI)较野生型明显减小,两者比较差异均有统计学意义(P0.05)。结论 2型糖尿病可能是通过瘦素受体参与的信号通路影响了骨量变化,为利用该模型进行DOP病因及治疗方法研究提供了新的方向。且在缺乏瘦素信号传导的情况下,骨质量和强度的降低验证了瘦素在体内起着合成代谢骨因子的作用。     

Cross-link profile of bone collagen correlates with structural organization of trabeculae

Little is known regarding the mechanisms that govern the structural organization of cancellous bone. In this study, we compare the nature of the collagen in vertebral cancellous bone with the structural organization of its trabecular network. Cylindrical specimens of cancellous bone from vertebrae were obtained from nine autopsy subjects (ages 46-88). In each subject, eight pairs of corresponding samples were obtained from three levels in the spine and three areas within the vertebral body, leading to a total of 68 pairs of samples. The cylinders from one side were used for morphometry and the classical morphometrical parameters were obtained (BV/TV, bone volume fraction; Tb.Th, trabecular thickness; Tb.N, number; Tb.Sp, trabecular spacing) and strut analysis (TSL, total strut length; Nd, number of nodes; Fe, number of free-ends). The amount of osteoid bone was also quantified. The cylinders from the other side were powdered and used for collagen assessment, including the amount of collagen (% w/w), and its content in immature cross-links; such as hydroxylysinonorleucine (mol/mol of collagen) and dihydroxylysinornorleucine, as well as stable mature cross-links, such as hydroxylysylpyridinoline (HP), lysylpyridinoline (LP), and the pyrrole cross-links. A random regression model was used to explore the correlations. None of the biochemical parameters correlated with the BV/TV except the ratio between immature and mature cross-links (eta(2) = 0.34, p < 0.05). There was no relationship between the amount of osteoid bone and the cross-link profile. However, the concentration of pyrrole and HP cross-links in the bone samples correlated with the structural organization of its trabeculae, but in an opposite direction. Hence, the pyrrole/HP ratio was a good predictor of Tb.Th, Tb.N, Tb.Sp, and TSL (eta(2) > 0.65 and p < 0.01) as well as Fe and star marrow space (eta(2) > 0.45 and p < 0.05). The cylinders from subjects with high pyrrole or low HP in their bone collagen had a relatively thick and simple structure. Those with low pyrrole and high HP had relatively thin trabeculae that were more numerous and spread over a complex network. The relative concentrations of the pyrrole and pyridinoline cross-links appear to reflect the structural organization of the trabeculae.     

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.     

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.     

Comparison of trabecular bone microarchitecture and remodeling in glucocorticoid-induced and postmenopausal osteoporosis.

Long-term treatment with glucocorticoids (GCs) leads to a rapid bone loss and to a greater risk of fractures. To evaluate the specific effects of this treatment on cancellous bone remodeling, structure, and microarchitecture, we compared 22 transiliac biopsy specimens taken in postmenopausal women (65 +/- 6 years) receiving GCs (> or = 7.5 mg/day, for at least 6 months) and 22 biopsy specimens taken in age-matched women with postmenopausal osteoporosis (PMOP), all untreated and having either at least one vertebral fracture or a T score < -2.5 SD. On these biopsy specimens, we measured static and dynamic parameters reflecting trabecular bone formation and resorption. Also, we performed the strut analysis and evaluated the trabecular bone pattern factor (TBPf), Euler number/tissue volume (E/TV), interconnectivity index (ICI), and marrow star volume (MaSV). Glucocorticoid-induced osteoporosis (GIOP), when compared with PMOP, was characterized by lower bone volume (BV/TV), trabecular thickness (Tb.Th), wall thickness (W.Th), osteoid thickness (O.Th), bone formation rate/bone surface (BFR/BS), adjusted mineral apposition rate/bone surface (Aj.AR/BS), and higher ICI and resorption parameters. After adjustment for BV/TV, the W.Th remained significantly lower in GIOP (p < 0.0001). The active formation period [FP(a+)] was not different. Patients with GIOP were divided into two groups: high cumulative dose GCs (HGCs; 23.7 +/- 9.7 g) and low cumulative dose GCs (LGCs; 2.7 +/- 1.2 g). HGC when compared with LGC was characterized by lower W.Th (p < 0.05), BV/TV (p < 0.001), Tb.Th (p < 0.05), trabecular number (Tb.N; p < 0.05), FP(a+)(p < 0.05), and nodes (p < 0.05), and higher E/TV (p < 0.05), ICI (p < 0.005), and TBPf (p < 0.05). When HGC was compared with PMOP, the results were similar except for the MaSV, which was significantly higher (p < 0.005). In summary, GIOP was characterized by lower formation and higher resorption than in PMOP, already present after LGC. With HGCs, these changes were associated with a more dramatic bone loss caused by a major loss of trabecular connectivity.     

Independent and combined contributions of cancellous and cortical bone deficits to vertebral fracture risk in postmenopausal women.

Using iliac bone histomorphometry on 78 patients with vertebral fracture and 66 healthy postmenopausal women, cortical thickness discriminated at least as well as any cancellous bone structural index between the two groups. Subjects with a deficit in both cortical and cancellous bone had much greater likelihood of fracture. INTRODUCTION: Vertebral fracture is often attributed to disproportional loss of cancellous bone, but fracture patients may have deficits in cortical and cancellous bone. Accordingly, we examined the contribution of cortical and cancellous bone deficits, separately and together, to the likelihood of vertebral fracture. MATERIALS AND METHODS: Iliac bone histomorphometry was performed in 78 white woman with clinically apparent vertebral fracture, 66 healthy postmenopausal women, and 38 healthy premenopausal women. We measured cancellous bone volume (Cn.BV/TV), trabecular number (Tb.N), trabecular thickness (Tb.Th), cortical bone volume (Ct.BV/TV), and cortical thickness (Ct.Th). For each variable, a value of >1 SD below the mean in premenopausal women was treated as a putative risk factor, and its association with the presence or absence of fracture was determined by OR calculated by logistic regression and by receiver operating characteristic (ROC) curve analysis. Subsets of fracture and control subjects were separately matched for Cn.BV/TV and Ct.Th. RESULTS: All structural indices differed between fracture patients and controls except Ct.BV/TV. There was a weak but highly significant correlation between Cn.BV/TV and Ct.Th in the entire group (r = 0.389, r(2) = 0.151 p < 0.001). Many control subjects had a high value for one of these variables and a low value for the other. Ct.Th., Cn.BV/TV, and Tb.N were all significantly associated with vertebral fracture (ORs, 4.4-5.8; ROC area under the curve [AUC], 0.74-0.85). In subjects matched for Cn.BV/TV, Ct.Th was reduced by 29% (OR, 5.0), and in subjects matched for Ct.Th, Cn.BV/TV was reduced by 27% (OR, 5.0). In patients with deficits in both cortical and cancellous bone, the ORs ( 28-35 ) were much higher. CONCLUSIONS: Deficits in cortical bone (reduced value for Ct.Th) and in cancellous bone (reduced values for Cn.BV/TV or Tb.N) were equally effective in discriminating between subjects with and without vertebral fracture. With a deficit in both cortical and cancellous bone, the association with vertebral fracture was much stronger. Vertebral fracture is not the result of disproportionate loss of cancellous bone in the patients as a whole, although individual patients may have relatively greater deficits in either cancellous or cortical bone.     

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.     

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.     

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。     

Cancellous Bone Properties and Matrix Content of TGF-β2 and IGF-I in Human Tibia: A Pilot Study

Transforming and insulin-like growth factors are important in regulating bone mass. Thus, one would anticipate correlations between matrix concentrations of growth factors and functional properties of bone. We therefore investigated the relationships of (1) TGF-β2 and (2) IGF-I matrix concentrations with the trabecular microstructure, stress distribution, and mechanical properties of tibial cancellous bone from six male human cadavers. Trabecular stress amplification (VMExp/σ_app) and variability (VMCOV) were calculated using microcomputed tomography (μCT)-based finite element simulations. Bone volume fraction (BV/TV), surface/volume ratio (BS/BV), trabecular thickness (Tb.Th), number (Tb.N) and separation (Tb.Sp), connectivity (Eu.N), and anisotropy (DA) were measured using 3-D morphometry. Bone stiffness and strength were measured by mechanical testing. Matrix concentrations of TGF-β2 and IGF-I were measured by ELISA. We found higher matrix concentrations of TGF-β2 were associated with higher Tb.Sp and VMExp/σ_app for pooled data and within subjects. Similarly, a higher matrix concentration of IGF-I was associated with lower stiffness, strength, BV/TV and Tb.Th and with higher BS/BV, Tb.Sp, VMExp/σ_app and VMCOV for pooled data and within subjects. IGF-I and Tb.N were negatively associated within subjects. It appears variations of the stress distribution in cancellous bone correlate with the variation of the concentrations of TGF-β2 and IGF-I in bone matrix: increased local matrix concentrations of growth factors are associated with poor biomechanical and architectural properties of tibial cancellous bone.     

Intervertebral disc disorganization is related to trabecular bone architecture in the lumbar spine.

Cancellous bone morphometry was investigated in the sagittal plane of lumbar vertebrae using histoquantitation. The aim of this study was to identify variations in cancellous bone architecture at increasing states of intervertebral disc (IVD) disorganization after age adjustment and to investigate regional variations within the whole vertebral body. Measurements were taken of the ratio of bone volume (BV) to total volume (TV), trabecular thickness (Tb.Th), trabecular separation (Tb.Sp), and trabecular number (Tb.N). Lumbar spines (T12-L5) of 19 men and 8 women were removed at autopsy from an adult sample with no clinical history of bone-related disease or histologically identifiable bone disease. It was found that degeneration of the IVD becomes more common with increasing age. After age-adjustment, significant increases in the proportion of BV/TV were observed in the presence of advancing IVD disorganization. Significant architectural changes were observed in the anterior regions of the vertebral body with increases in Tb.Th and Tb.N and decreases in Tb.Sp. Minimal alterations were found at posterior regions. Bone loss was observed in central regions (most distant from the cortex) as IVD disorganization increased through reduction in both Tb.N and Tb.Th. The BV/TV increase in anterior areas of the centrum may be a response to a redistribution of load to the vertebral body periphery as a result of IVD disorganization. It appears that trabecular morphology is related to the condition of the associated IVD, rather than being the sole consequence of a loss of BV/TV with age. This relationship could influence the occurrence of vertebral body crush fracture.     

Risedronate preserves bone architecture in postmenopausal women with osteoporosis as measured by three-dimensional microcomputed tomography

The deterioration of trabecular microarchitecture induced by elevated bone turnover is increasingly recognized as a factor in the pathogenesis of osteoporotic fractures. We investigated the effect of the reduction of turnover with risedronate on trabecular architecture in postmenopausal women with osteoporosis. Iliac crest bone biopsy specimens taken before and after 3 years of treatment from patients receiving risedronate 5 mg daily (n = 21) or placebo (n = 17) were analyzed using 3-D microcomputed tomography. We found a significant correlation between baseline bone turnover and bone loss in the placebo group, providing evidence that higher turnover induced higher bone loss leading to a greater degree of architectural degradation. When patients were classified into two groups based on baseline bone turnover (MS/BS less than or greater than the median value for the entire cohort), significant decreases in trabecular bone volume (BV/TV, P = 0.009) and trabecular thickness (Tb.Th*, P = 0.008) and an increase in marrow star volume (Ma.St.V, P = 0.008), a measure of trabecular porosity, were observed in the higher turnover (MS/BS> median) placebo-treated patients. The trabecular structure shifted from plates to rods as shown by an increase in structure model index (SMI, P = 0.028) and bone surface to bone volume ratio (BS/BV, P = 0.006). The changes from baseline in the lower turnover (MS/BS相似文献   

Mapping quantitative trait loci for vertebral trabecular bone volume fraction and microarchitecture in mice.

BMD, which reflects both cortical and cancellous bone, has been shown to be highly heritable; however, little is known about the specific genetic factors regulating trabecular bone. Genome-wide linkage analysis of vertebral trabecular bone traits in 914 adult female mice from the F2 intercross of C57BL/6J and C3H/HeJ inbred strains revealed a pattern of genetic regulation derived from 13 autosomes, with 5-13 QTLs associated with each of the traits. Ultimately, identification of genes that regulate trabecular bone traits may yield important information regarding mechanisms that regulate mechanical integrity of the skeleton. INTRODUCTION: Both cortical and cancellous bone influence the mechanical integrity of the skeleton, with the relative contribution of each varying with skeletal site. Whereas areal BMD, which reflects both cortical and cancellous bone, has been shown to be highly heritable, little is known about the genetic determinants of trabecular bone density and architecture. MATERIALS AND METHODS: To identify heritable determinants of vertebral trabecular bone traits, we evaluated the fifth lumbar vertebra from 914 adult female mice from the F2 intercross of C57BL/6J (B6) and C3H/HeJ (C3H) progenitor strains. High-resolution microCT was used to assess total volume (TV), bone volume (BV), bone volume fraction (BV/TV), trabecular thickness (Tb.Th), separation (Tb.Sp), and number (Tb.N) of the trabecular bone in the vertebral body in the progenitors (n = 8/strain) and female B6C3H-F2 progeny (n = 914). Genomic DNA from F2 progeny was screened for 118 PCR-based markers discriminating B6 and C3H alleles on all 19 autosomes. RESULTS AND CONCLUSIONS: Despite having a slightly larger trabecular bone compartment, C3H progenitors had dramatically lower vertebral trabecular BV/TV (-53%) and Tb.N (-40%) and higher Tb.Sp (71%) compared with B6 progenitors (p < 0.001 for all). Genome-wide quantitative trait analysis revealed a pattern of genetic regulation derived from 13 autosomes, with 5-13 quantitative trait loci (QTLs) associated with each of the vertebral trabecular bone traits, exhibiting adjusted LOD scores ranging from 3.1 to 14.4. The variance explained in the F2 population by each of the individual QTL after adjusting for contributions from other QTLs ranged from 0.8% to 5.9%. Taken together, the QTLs explained 22-33% of the variance of the vertebral traits in the F2 population. In conclusion, we observed a complex pattern of genetic regulation for vertebral trabecular bone volume fraction and microarchitecture using the F2 intercross of the C57BL/6J and C3H/HeJ inbred mouse strains and identified a number of QTLs, some of which are distinct from those that were previously identified for total femoral and vertebral BMD. Identification of genes that regulate trabecular bone traits may ultimately yield important information regarding the mechanisms that regulate the acquisition and maintenance of mechanical integrity of the skeleton.     

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.     

仿生双相磷酸钙生物陶瓷支架的Micro-CT评价

[目的]体外用Micro-CT(Micro-computed tomography)图像对仿生双相磷酸钙生物陶瓷支架的三维结构进行计算机重建和评价.[方法]犬股骨头的松质骨样本行Micro-CT扫描,提取图像信息;三维凝胶叠层成型法制备出具有仿骨小梁结构的双相磷酸钙仿生生物陶瓷支架.随后用Micro-CT对支架扫描,以三维结构参数对支架和松质骨样本作三维评价和比较.三维参数包括:骨体积分数(Bone Volume Fraction,BVF,BV/TV)、骨表面积体积比(Bone surface/bone volume ratio,BS/BV)、骨小梁厚度(Trabecular thickness,TbTh)、骨小梁数目(Trabecular number,TbN)、骨小梁间隙(Trabecular spacing,TbSp)、结构模型指数(Structure Model Index,SMl)和各向异性程度(degree of anisoropy,DA).[结果]与犬股骨头松质骨样本相比,用本方法制备出的BCP支架具有相似的三维空间结构,二者的BV/TV、TbTh、TbN无显著差别(P＞0.05).小梁结构呈板状模型.[结论]本研究制备的BCP多孔支架的小梁具有一定的取向性,力学强度和良好的适于血管长入的空间结构.