Tor Hildebrand

Direct three-dimensional morphometric analysis of human cancellous bone : microstructural data from spine, femur, iliac crest and calcaneus

The appearance of cancellous bone architecture is different for various skeletal sites and various disease states. During aging and disease, plates are perforated and connecting rods are dissolved. There is a continuous shift from one structural type to the other. So traditional histomorphometric procedures, which are based on a fixed model type, will lead to questionable results. The introduction of three‐dimensional (3D) measuring techniques in bone research makes it possible to capture the actual architecture of cancellous bone without assumptions of the structure type. This requires, however, new methods that make direct use of the 3D information. Within the framework of a BIOMED I project of the European Union, we analyzed a total of 260 human bone biopsies taken from five different skeletal sites (femoral head, vertebral bodies L2 and L4, iliac crest, and calcaneus) from 52 donors. The samples were measured three‐dimensionally with a microcomputed tomography scanner and subsequently evaluated with both traditional indirect histomorphometric methods and newly developed direct ones. The results show significant differences between the methods and in their relation to the bone volume fraction. Based on the direct 3D analysis of human bone biopsies, it appears that samples with a lower bone mass are primarily characterized by a smaller plate‐to‐rod ratio, and to a lesser extent by thinner trabecular elements.

Non-invasive bone biopsy: a new method to analyse and display the three-dimensional structure of trabecular bone

Three-dimensional structure is one of the main factors influencing the mechanical behaviour of cancellous bone. To analyse the trabecular bone structure non-destructively we used a peripheral QCT system and applied a special thin-slice technique to create high-resolution volumetric data sets serving as a basis for something we would like to call non-invasive bone biopsy. In order to obtain binary data sets, the mineralized bone in the CT volume was separated from bone marrow and muscle tissue with the help of a sophisticated three-dimensional segmentation algorithm based on the analysis of directional derivatives, which are computed from a locally approximated fit function of the original CT volume. Binary volumes including either a solid representation of trabecular plates and rods or a topological representation of the cancellous bone architecture were acquired. Such volumes can be processed non-destructively and, even more important, repetitively. By using a surface reconstruction algorithm based on interpolating triangulation it was possible to visualize the three-dimensional surface of the trabecular bone structure. The results showed that surface representation and visualization in combination with a multiple thin-slice measuring technique are valuable tools in studying three-dimensional bone architecture. In the future, the non-invasive bone biopsies will be evaluated by means of three-dimensional mechanical analysis incorporating finite element modelling and direct morphological investigations of the cancellous bone architecture for a better prediction of bone strength as an index for fracture risk or osteoporosis.

Do quantitative ultrasound measurements reflect structure independently of density in human vertebral cancellous bone

Ultrasonic measurements were made in three orthogonal directions on 70 vertebral bone cubes. Apparent density (rho) was determined, and microcomputed tomography was used to derive a range of microstructural parameters. Qualitatively different ultrasonic behavior was observed in the craniocaudal (CC) axis, in which two distinct waves propagated. In this direction, only attenuation correlated strongly with rho (r2 = 80%), whereas, in the anteroposterior (AP) and mediolateral (ML) axes, there were significant correlations between all ultrasonic parameters and rho (r2 = 57%-79%). Microstructural parameters were, in general, correlated with ultrasonic properties, but when adjusted for rho, few significant relationships remained and the additional variance explained by individual microstructural parameters was relatively small (< 25% for CC axis, < 3% for AP, 0% for ML). In stepwise regression analysis including rho and all of the microstructural parameters, rho remained the primary determinant of ultrasonic properties in the transverse axes: Combinations of structural parameters explained, at most, an additional of 6% of the variability in ultrasonic properties in the AP axis, but failed to contribute significantly in the ML axis. In the CC axis, structural parameters played a greater role, but the pattern of associations was complex and the predictive power of the models was generally much less than that for the transverse axes. These data indicate that the ability of ultrasound to reflect aspects of trabecular structure is strongly dependent on the direction in which ultrasonic measurements are made, and provide only qualified support for the hypothesis that ultrasound reflects cancellous bone structure independently of bone density.

Bone structure as revealed by microtomography

The appearance of cancellous bone architecture is different for various skeletal sites and various disease states. In the iliac crest it is more plate-like, whereas in the spine rods dominate. During aging and disease plates are perforated and connecting rods are dissolved. There is a continuous shift from one structural type to the other. So traditional histomorphometric procedures, which are based on a fixed model type, will lead to questionable results. 3D microtomography allows to assess model independent structural parameters so that trabecular thickness, for example, can be determined directly. Not only mean thicknesses are available but also thickness histograms which are helpful to identify pathological states. Other features such as trabecular separation, degree of anisotropy and structural type index can be extracted from the 3D images and allow to characterize cancellous bone and its changes due to aging, disease and treatment. To fully exploit the significance of bone structure on bone strength large scale finite element (FE) analyses are performed. Hence microtomography, performed with a sufficiently fine isotropic spatial resolution, reveals information on the structural features of cancellous bone which were not available so far and which will, hopefully, lead to a better understanding of the pathogenesis of bone diseases and subsequently to improved treatment regimes.