Longitudinal micro-CT scans to evaluate bone architecture.

For a long time bone mass or BMD has been considered as the main predictor for fracture risk in the clinic. In laboratory experiments bone mass or bone volume fraction is a reasonable good predictor of cancellous bone mechanical properties i.e., stiffness and strength. Obviously, since bone volume fraction is a scalar property it cannot predict all cancellous bone mechanical properties in highly anisotropic regions. It has become clear that bone mass or BMD has strong shortcomings for the prediction of fracture risk. The new paradigm is to measure bone quality as a surrogate for fracture risk. However, there is no clear definition of bone quality. Many architectural parameters have been measured in cancellous bone and have been tested on their ability to predict fracture risk independent of bone mass. For most of those measures of bone architecture it is not clear what the relation is with mechanical properties or fracture risk. Trabecular anisotropy seems to be the most promising parameter so far that might be useful as an independent contributor to fracture risk 1,2,3 , likely due to a relatively weak structure in the direction of the infrequent off-axis loading direction 4 . The measurement of bone architecture has a long history with a gold standard based on histology. Stereological methods were applied to estimate the three-dimensional architecture from the two-dimensional histological slices. In addition to the morphological descriptions and estimates of the three-dimensional architecture, histology offers a number of other important measures such as the unmineralized osteoid surface, cell counts of osteoblasts and osteoclasts and most important a measure of bone formation rate through use of fluorescent labels incorporated in the mineralizing front. These latter advantages have resulted in the technique still being in widespread use, even though it has big disadvantages like biased two-dimensional (indirect) measuring of bone morphometry parameters and labor intensiveness. Around 1990 a high-resolution version of the clinical CT scanner was introduced in the research laboratory 5 , and has become an important modality for bone morphometry measurements. The apparatus yields true 3-dimensional data sets of bone biopsies and whole bones of small animals like the mouse and rat. Voxel sizes can be as small as 5 microns or less. The advantages of this modality above histological sections are the unbiased 3-D morphometric measures of bone architecture, and that the samples can be imaged non-destructively so the bones are available for other measuring techniques such as e.g., failure tests. The popularity of the device led to a wild growth of new parameters that claim to measure important aspects of bone architecture, ranging from accepted measures like volume fraction and trabecular thickness to more exotic measures like Gaussian curvature and fractal dimensions. It is not clear which of these parameters are useful and what they tell us about bone structure or quality. A standardization of these measures would be useful, just like the standardization in parameters led by Parfitt et al., 6 following a similar explo