PMID: 12464744

Issn Print: 0899-3459

Publication Date: 2002/10/01


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The Zürich Experience: One Decade of Three-Dimensional High-Resolution Computed Tomography

Ralph Müller

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Excerpt

Bone mineral measurements frequently are used to diagnose metabolic bone diseases such as osteoporosis. Before age 50 years, such diseases affect only a few people, whereas in old age, few individuals are left without fractures due to age-or disease-related reduction of bone strength. Although many older persons may lose bone, as expressed by a decrease in bone density, not all develop fractures. This is not unexpected, as bone density is not the sole determinant of fracture risk. Neuromuscular function and environmental hazards influencing the risk of fall, force of impact, and bone strength are equally important factors (1). Bone mineral density (BMD), geometry of bone, microarchitecture of bone, and quality of the bone material all are components that determine bone strength as defined by the bone's ability to withstand loading. On average, 70–80% of the variability in bone strength in vitro is determined by its density (2). On an individual basis, density alone accounts for 10–90% of the variation in the strength of trabecular bone (3). This also means that 90–10% of the variation in strength cannot be explained by bone density. Preliminary data have shown that predicting trabecular bone strength can be greatly improved by including architectural parameters in the analysis (4–6).
Quantitative bone morphometry is a method to assess structural properties of the trabecular bone. Trabecular morphometry traditionally has been assessed in two dimensions, where the structural parameters are either inspected visually or measured from sections, and the third dimension is added on the basis of stereology (7,8). The conventional approach to morphologic measurements typically entails substantial preparation of the specimen, including embedding in methylmethacrylate, followed by sectioning into slices. Although the method offers high spatial resolution and high image contrast (Fig. 1A and B), it is a tedious and time-consuming technique. Particularly limiting is the destructive nature of the procedure, which prevents the specimen from being used for other measurements such as analysis in different planes. The latter is highly desirable because of the anisotropic nature of trabecular bone (9–11). To overcome some of the limitations of the analysis of two-dimensional (2D) histologic sections, several three-dimensional (3D) measurement and analysis techniques are being investigated. Traditionally, the most common technique is the use of stereo-or scanning microscopy to assess 3D structural indices qualitatively. In using these methods researchers were able to demonstrate the loss of 3D connectivity in the trabecular network with age and the involved modeling processes and sites by visual observation (12). Structural age dependency also could be demonstrated by using a surface-stained block grinding technique that allowed a semiquantitative combined 2d and 3D histomorphometric analysis of the spine with the help of stereomicroscopy (13). In the past, the method of serial sectioning has been used to explore the third dimension quantitatively (14). This technique provides 3D images of trabecular bone with high resolution and high quality where the 3D structure is reconstructed based on microscopic optical images from individual contiguous sections. However, the method also entails substantial preparation of the specimen, including embedding in black resin, followed by sectioning into thin slices as well as surface treatment of contrast enhancement. With such methods, quantitative measurement of 3D connectivity and other structural properties such as volume fraction and surface area are possible on a truly 3D basis. Nevertheless, by using such preparation the bone samples are no longer available for other static and dynamic histomorphometric analyses. Also, being truly destructive, the serial sectioning technique does not allow subsequent mechanical testing or other secondary measurements because the samples are destroyed during sample preparation.

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