Fat mass impacts on both bone turnover and bone density and is a critical risk factor for osteoporotic fractures. Adipocyte-derived hormones may contribute to this relationship, and adiponectin is a principal circulating adipokine. However, its effects on bone remain unclear. We have, therefore, investigated the direct effects of adiponectin on primary cultures of osteoblastic and osteoclastic cells in vitro and determined its integrated effects in vivo by characterizing the bone phenotype of adiponectin-deficient mice. Adiponectin was dose-dependently mitogenic to primary rat and human osteoblasts ( approximately 50% increase at 10 microg/ml) and markedly inhibited osteoclastogenesis at concentrations of 1 microg/ml or greater. It had no effect on osteoclastogenesis in RAW-264.7 cells or on bone resorption in isolated mature osteoclasts. In adiponectin knockout (AdKO) male C57BL/6J mice, trabecular bone volume and trabecular number (assessed by microcomputed tomography) were increased at 14 wk of age by 30% (P = 0.02) and 38% (P = 0.0009), respectively. Similar, nonsignificant trends were observed at 8 and 22 wk of age. Biomechanical testing showed lower bone fragility and reduced cortical hardness at 14 wk. We conclude that adiponectin stimulates osteoblast growth but inhibits osteoclastogenesis, probably via an effect on stromal cells. However, the AdKO mouse has increased bone mass, suggesting that adiponectin also has indirect effects on bone, possibly through modulating growth factor action or insulin sensitivity. Because adiponectin does influence bone mass in vivo, it is likely to be a contributor to the fat-bone relationship.

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In vitro and in vivo effects of adiponectin on bone

A shape-analysis algorithm statically analyzes a program to determine information about the heap-allocated data structures that the program manipulates. The results can be used to understand or verify programs. They also contain information valuable for debugging, compile-time garbage collection, instruction scheduling, and parallelization.

Shape Analysis

The roles of microarchitecture and types of trabeculae in determining elastic modulus of trabecular bone have been studied in μCT images of 29 trabecular bone samples by comparing their Young's moduli calculated by finite element analysis (FEA) with different trabecular type-specific reconstructions. The results suggest that trabecular plates play an essential role in determining elastic properties of trabecular bone.



Introduction: Osteoporosis is an age-related disease characterized by low bone mass and architectural deterioration. Other than bone volume fraction (BV/TV), microarchitecture of bone is also believed to be important in governing mechanical properties of trabecular bone. We quantitatively examined the role of microarchitecture and relative contribution of trabecular types of individual trabecula in determining the elastic property of trabecular bone.



Materials and Methods: Twenty-nine human cadaveric trabecular bone samples were scanned at 21-μm resolution using a μCT system. Digital topological analysis (DTA) consisting of skeletonization and classification was combined with a trabecular type-specific reconstruction technique to extract the skeleton and identify topological type of trabeculae of the original trabecular bone image. Four different μCT-based finite element (FE) models were constructed for each specimen: (1) original full voxel; (2) skeletal voxel; (3) rod-reconstructed, preserving rod volume and plate skeleton; and (4) plate-reconstructed, preserving plate volume and rod skeleton. For each model, the elastic moduli were calculated under compression along each of three image-coordinate axis directions. Plate and rod tissue fractions directly measured from DTA-based topological classification were correlated with the elastic moduli computed from full voxel model.



Results: The elastic moduli of skeleton models were significantly correlated with those of full voxel models along all three coordinate axes (r2 = 0.38−0.53). The rod-reconstructed model contained 21.3% of original bone mass and restored 1.5% of elastic moduli, whereas the plate-reconstructed model contained 90.3% of bone mass and restored 53.2% of elastic moduli. Plate tissue fraction showed a significantly positive correlation (r2 = 0.49) with elastic modulus by a power law, whereas rod tissue fraction showed a significantly negative correlation (r2 = 0.42).



Conclusions: These results quantitatively show that the microarchitecture alone affects elastic moduli of trabecular bone and trabecular plates make a far greater contribution than rods to the bone's elastic behavior.

Quantification of the Roles of Trabecular Microarchitecture and Trabecular Type in Determining the Elastic Modulus of Human Trabecular Bone

UNLABELLED: Morphometric analysis of 70 bone biopsies was done in parallel by microCT and histomorphometry. microCT provided higher results for trabecular thickness and separation because of the 3D shape of these anatomical objects. INTRODUCTION: Bone histomorphometry is used to explore the various metabolic bone diseases. The technique is done on microscopic 2D sections, and several methods have been proposed to extrapolate 2D measurements to the 3D dimension. X-ray microCT is a recently developed imaging tool to appreciate 3D architecture. Recently the use of 2D histomorphometric measurements have been shown to provide discordant results compared with 3D values obtained directly. MATERIAL AND METHODS: Seventy human bone biopsies were removed from patients presenting with metabolic bone diseases. Complete bone biopsies were examined by microCT. Bone volume (BV/TV), Tb.Th, and Tb.Sp were measured on the 3D models. Tb.Th and Tb.Sp were measured by a method based on the sphere algorithm. In addition, six images were resliced and transferred to an image analyzer: bone volume and trabecular characteristics were measured after thresholding of the images. Bone cores were embedded undecalcified; histological sections were prepared and measured by routine histomorphometric methods providing another set of values for bone volume and trabecular characteristics. Comparison between the different methods was done by using regression analysis, Bland-Altman, Passing-Bablock, and Mountain plots. RESULTS: Correlations between all parameters were highly significant, but microCT overestimated bone volume. The osteoid volume had no influence in this series. Overestimation may have been caused by a double threshold used in microCT, giving trabecular boundaries less well defined than on histological sections. Correlations between Tb.Th and Tb.Sp values obtained by 3D or 2D measurements were lower, and 3D analysis always overestimated thickness by approximately 50%. These increases could be attributed to the 3D shape of the object because the number of nodes and the size of the marrow cavities were correlated with 3D values. CONCLUSION: In clinical practice, microCT seems to be an interesting method providing reliable morphometric results in less time than conventional histomorphometry. The correlation coefficient is not sufficient to study the agreement between techniques in histomorphometry. The architectural descriptors are influenced by the algorithms used in 3D.

Comparison Insight Bone Measurements by Histomorphometry and μCT

Trabecular bone microarchitecture: A review

Trabecular bone has been reported as having two-dimensional (2-D) fractal characteristics at the histological level, a finding correlated with biomechanical properties However, several fractal dimensions (D) are known and computational ways to obtain them vary considerably This study compared three algorithms on the same series of bone biopsies, to obtain the Kolmogorov, Minkowski-Bouligand, and mass-radius fractal dimensions The relationships with histomorphometric descriptors of the 2-D trabecular architecture were investigated Bone biopsies were obtained from 148 osteoporotic male patients Bone volume (BV/TV), trabecular characteristics (TbN, TbSp, TbTh), strut analysis, star volumes (marrow spaces and trabeculae), inter-connectivity index, and Euler-Poincare number were computed The box-counting method was used to obtain the Kolmogorov dimension (D(k)), the dilatation method for the Minkowski-Bouligand dimension (D(MB)), and the sandbox for the mass-radius dimension (D(MR)) and lacunarity (L) Logarithmic relationships were observed between BV/TV and the fractal dimensions The best correlation was obtained with D(MR) and the lowest with D(MB) Lacunarity was correlated with descriptors of the marrow cavities (ICI, star volume, TbSp) Linear relationships were observed among the three fractal techniques which appeared highly correlated A cluster analysis of all histomorphometric parameters provided a tree with three groups of descriptors: for trabeculae (TbTh, strut); for marrow cavities (Euler, ICI, TbSp, star volume, L); and for the complexity of the network (TbN and the three D's) A sole fractal dimension cannot be used instead of the classic 2-D descriptors of architecture; D rather reflects the complexity of branching trabeculae Computation time is also an important determinant when choosing one of these methods

Fractal dimension of trabecular bone: comparison of three histomorphometric computed techniques for measuring the architectural two-dimensional complexity

Bernard Auvinet

Papers

Fractal dimension of trabecular bone: comparison of three histomorphometric computed techniques for measuring the architectural two-dimensional complexity