Recent advances in understanding the molecular and genetic basis of osteoporosis have been very promising, and with the advent of new emergent therapies, one of the requirements will be the ability to assess non-invasively, measures of trabecular architecture and mechanical strength, and predict the efficacy of different therapeutic regimes. In this context bone quality and strength may depend on several factors apart from bone density such as trabecular architecture. Recent efforts, have been directed towards estimating trabecular structure non- invasive using fractal analysis techniques to quantify trabecular pattern in radiographs. Preliminary experiments of the application of these techniques to the analysis of radiographs appears promising and computerized assessment of bone structure and fracture risk assessment using radiographs is a novel idea with far-reaching applications. However, a basic understanding of what the techniques are measuring relative to known parameters of biomechanical competence and trabecular architecture is a fundamental requirement before the widespread clinical use of such techniques. The primary hypothesis of this study is that non invasive, quantitative measures of trabecular bone architecture from radiographs derived using fractal analysis techniques are related to the trabecular bone architecture as determined using histomorphometry measures and predicts biomechanical properties of trabecular bone. Furthermore understanding the complex relationship between such quantitative radiographic analysis, biomechanical competence and histomorphometry of trabecular bone will establish the efficacy and basis for the widespread, routine use of these methods for assessing trabecular bone architecture. Specifically the study is designed to develop fractal analysis techniques of radiographs for the quantification of trabecular architecture in cubic specimen of human trabecular bone from the lumbar spine, distal radius, calcaneus and proximal femur and relate the fractal characteristics of the radiographs measured in three orthogonal projections to (a) the biomechanical elastic modulus of the specimen as assessed by non-destructive testing along the three orthogonal directions, (b) the biomechanical strength of the specimen as assessed by destructive testing a randomized direction in a subset of samples, (c) measures of trabecular bone structure such as the mean trabecular width, trabecular number, trabecular spacing, fractional trabecular bone area etc. measured using standard histomorphometry techniques, (d) the three dimensional structure such as connectivity measured using high resolution magnetic resonance images. This study is not designed as an extensive clinical trial in a large number of patients, thus after deriving the basic relationship underlying quantitative radiographic analysis and trabecular bone architecture and biomechanical competence, the aim is to do a case controlled prospective study, in two groups of post-menopausal women (100 each), those with vertebral fractures and those without, and determine whether such analyses adds significantly to fracture risk prediction compared to bone mineral density of the lumbar spine as measured using dual x-ray absorptometry. The significance of the proposed study lies in the fact that it focuses on the analysis of radiographs, a relatively inexpensive imaging modality, which if successful would find widespread application. In the context of the specific research initiative it this study is an inter- disciplinary study that combines and fosters interactions between bone biology investigators, physicists, clinical radiologists, mechanical engineers, to investigate a novel approach to non-invasively measure trabecular bone structure and mechanical properties, and aims to develop a basic relationship between established techniques and an new experimental approach.
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