Peter Rüegsegger

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.

A microtomographic system for the nondestructive evaluation of bone architecture

Microtomography (micro-computed-tomography, μ-CT) is a method to image and quantify trabecular bone. It has the capability to address the role of trabecular architecture on the mechanical properties of bone and to study trabecular bone remodeling. The system described in this work is based on a compact fan-beam type tomograph that can work in spiral scanning or multislice mode. An X-ray tube with a microfocus is used as a source, a CCD-array as a detector. Samples with diameters from a few millimeters to a maximum of 14 mm can be measured, typically, bone biopsies with a diameter of 8 mm and a length of approximately 10 mm are measured. Spatial resolution is 28 μm. Usually the volume of interest contains 4×4×4 mm3 and is represented in 14×14×14 μm3 voxels. 3D stereological indices are extracted according to the standard definitions used in histomorphometry. Triangular surface representation is effected with an extended marching cube algorithm and forms a convenient basis for finite element analysis. Microtomographic measurements may be employed to “calibrate” lower-dose, lower-resolution imagesin vivo as well as to nondestructively assess unprocessed surgical bone biopsy specimens. These specimens remain intact for mechanical or histological testing.

Estimation of distal radius failure load with micro-finite element analysis models based on three-dimensional peripheral quantitative computed tomography images

There is increasing evidence that, in addition to bone mass, bone microarchitecture and its mechanical load distribution are important factors for the determination of bone strength. Recently, it has been shown that new high-resolution imaging techniques in combination with new modeling algorithms based on the finite element (FE) method can account for these additional factors. Such models thus could provide more relevant information for the estimation of bone failure load. The purpose of the present study was to determine whether results of whole-bone micro-FE (microFE) analyses with models based on three-dimensional peripheral quantitative computer tomography (3D-pQCT) images (isotropic voxel resolution of 165 microm) could predict the failure load of the human radius more accurately than results with dual-energy X-ray absorptiometry (DXA) or bone morphology measurements. For this purpose, microFE models were created using 54 embalmed cadaver arms. It was assumed that bone failure would be initiated if a certain percentage of the bone tissue (varied from 1% to 7%) would be strained beyond the tissue yield strain. The external force that produced this tissue strain was calculated from the FE analyses. These predictions were correlated with results of real compression testing on the same cadaver arms. The results of these compression tests were also correlated with results of DXA and structural measurements of these arms. The compression tests produced Colles-type fractures in the distal 4 cm of the radius. The predicted failure loads calculated from the FE analysis agreed well with those measured in the experiments (R(2) = 0.75 p < 0.001). Lower correlations were found with bone mass (R(2) = 0.48, p < 0.001) and bone structural parameters (R(2) = 0.57 p < 0.001). We conclude that application of the techniques investigated here can lead to a better prediction of the bone failure load for bone in vivo than is possible from DXA measurements, structural parameters, or a combination thereof.

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.

Calibration of trabecular bone structure measurements of in vivo three-dimensional peripheral quantitative computed tomography with 28-μm-resolution microcomputed tomography

It has recently been shown that high-resolution computed tomography and magnetic resonance imaging have the potential to assess information about the microarchitecture of bone in a noninvasive way. However, due to the limited spatial resolution of the in vivo measurements, the individual trabeculae are not depicted with their true thickness. Nevertheless, the spacing of the structural elements allows the assessment of trabecular number. In a previous publication, the ridge number density (RND) was introduced as a measure for this structural index. It can be extracted from high-resolution three-dimensional (3D) images of patients and shows a reproducibility of 1.6%. In this work the Ridge extraction procedure is compared to and calibrated with microcomputed tomography (microCT) measurements. Three-dimensional measurements of 15 bone biopsies are made with a 28-microm-resolution microCT scanner as well as with a 165-microm-resolution peripheral quantitative computed tomography (pQCT) scanner. For the latter, the same settings are used as for patient examinations. The 15 pairs of measurements are analyzed and the resulting structural indices are compared. The results show that structural indices such as trabecular number, mean thickness, and mean separation can be determined from the 3D pQCT data with an r2 of between 0.81 and 0.96 if the microCT data are taken as the gold standard. The calibration equation found for the bone volume fraction has an intercept of 0.04 and a slope of 0.86 (r2 = 0.98), and trabecular number as the main additional structural index shows a nonsignificant intercept and a calibration slope of 0.91 with the microCT. The calibration procedure can be used directly for patient examinations. Applied to time-series measurements it may be of value for monitoring and quantifying microarchitectural changes due to therapy or aging.

Corticosteroid-induced bone loss. A longitudinal study of alternate day therapy in patients with bronchial asthma using quantitative computed tomography

SummaryTreatment with corticosteroids can produce osteoporosis. It is generally held that bone loss occurs when steroids are administered daily, but recent findings indicate that bone may also be lost on alternate day therapy. Cortical and trabecular bone, which may be affected differently, can be assessed independently, by quantitative computed tomography. This technique has been applied to the appendicular skeleton in following 20 patients with bronchial asthma during one year of chronic alternate day corticosteroid therapy. The trabecular bone loss was considerable; prednisone 25 mg on alternate days caused an average reduction in trabecular bone of 3.5% over one year. Bone loss was dose- and agedependent. Young patients on 50 mg/2 days lost up to 17% trabecular bone in one year. Cortical bone was not significantly affected over the same period.

Finite element analysis of trabecular bone structure: a comparison of image-based meshing techniques

In this study, we investigate if finite element (FE) analyses of human trabecular bone architecture based on 168 microm images can provide relevant information about the bone mechanical characteristics. Three human trabecular bone samples, one taken from the femoral head, one from the iliac crest, and one from the lumbar spine, were imaged with micro-computed tomography (micro-CT) using a 28 microm resolution. After reconstruction the resolution was coarsened to 168 microm. First, all reconstructions were thresholded and directly converted to FE-models built of hexahedral elements. For the coarser resolutions of two samples, this resulted in a loss of trabecular connections and a subsequent loss of stiffness. To reduce this effect, a tetrahedral element meshing based on the marching cubes algorithm, as well as a modified hexahedron meshing, which thresholds the image such that load carrying bone mass is preserved, were employed. For each sample elastic moduli and tissue Von Mises stresses of the three different 168 microm models were compared to those from the hexahedron 28 microm model. For one sample the hexahedron meshing at 168 microm produced excellent results. For the other two samples the results obtained from the hexahedral models at 168 microm resolution were poor. Considerably better results were attained for these samples when using the mass-compensated or tetrahedron meshing techniques. We conclude that the accuracy of the FE-models at 168 microm strongly depends on the bone morphology, in particular its trabecular thickness. A substantial loss of trabecular connections during the hexahedron meshing process indicates that poor FE results will be obtained. In this case the tetrahedron or mass-compensated hexahedron meshing techniques can reduce the loss of connections and produce better results than the plain hexahedron meshing techniques.

Trabecular bone tissue strains in the healthy and osteoporotic human femur

Quantitative information about bone tissue‐level loading is essential for understanding bone mechanical behavior. We made microfinite element models of a healthy and osteoporotic human femur and found that tissue‐level strains in the osteoporotic femoral head were 70% higher on average and less uniformly distributed than those in the healthy one.

Morphometric analysis of noninvasively assessed bone biopsies: Comparison of high-resolution computed tomography and histologic sections

This article describes a new method to analyze the structural behavior of trabecular bone structure by means of noninvasive measurements of the three-dimensional cancellous bone architecture. For the noninvasive data acquisition, a high-resolution quantitative computed tomography system for peripheral measuring sites (pQCT) was used. With this system and the help of a multiple thin-slice measuring technique, it became possible to examine three-dimensional bone structure with a resolution of 0.25 mm. Using a special three-dimensional segmentation algorithm, mineralized bone was separated from bone marrow and muscle tissue within the three-dimensional stack of CT slices. These segmented data sets can then be processed nondestructively and, even more important, repetitively in either two or three dimensions. In order to validate this noninvasive procedure, a two-dimensional comparative morphometric study was performed including CT slices and corresponding histologic sections prepared after CT measurement. Three representative sections from the three-dimensional stack of CT slices were selected and the morphometric indices of the segmented CT slices were compared with the indices stemming from the corresponding histologic sections prepared after CT measurement. Although the presented approach can only give an example of the method, the results from the morphometric analysis support the assumption that cancellous bone structures based on noninvasive high-resolution CT measurements are representative for trabecular microstructures assessed from histologic bone sections. The study demonstrates the potential of high-resolution CT imaging for in vivo applications of quantitative bone morphometry. This is especially true for repetitive follow-up measurements, which cannot be performed using histologic sections. Additionally, the method offers an easy access to the three-dimensional structure of trabecular bone, which is mandatory for the analyses of the anisotropic mechanical behavior of cancellous bone.

Ridge number density: A new parameter for in vivo bone structure analysis

An advanced analysis of the mechanical properties of bone should include information about the microarchitecture of cancellous bone in addition to its density. It has recently been shown that high-resolution quantitative computed tomography and magnetic resonance imaging have the potential to assess such information in a noninvasive way in patients. Both techniques, however, lack sufficient spatial resolution to image the individual trabeculae with true precision. In this work, a new parameter, Ridge number density (RND), is introduced. RND is a measure for the trabecular number, which can be extracted directly from high-resolution three-dimensional (3D) images of patients. We applied the RND technique to a test group of nine healthy, postmenopausal women measured repetitively with a high-resolution 3D peripheral quantitative computed tomography (3D-pQCT) system with 165 x 165 x 165 microm3 voxel size. Simultaneously with the RND determination, the trabecular bone density (TBD) was also assessed in the same volume of interest. The examination site was the distal radius. The intersubject variability of the measured test group was 10.5% for RND and 26.3% for TBD. The root mean square error between first and second examinations (midterm reproducibility) was 1.6% and 1.1%, respectively. RND is determined independently from TBD and pertains to the structure of the cancellous bone. As such, it might add crucial information in cases where bone mass or bone density measurements alone give ambiguous results.