Osteoporosis is a debilitating disease causing skeletal impairment resulting from loss of cancellous and cortical bone, eventually leading to fractures of the femur, vertebrae, wrist and humerus. Current methods for assessment of skeletal competence rely almost entirely on bone mineral density (BMD), which is widely considered the primary risk factor for the occurrence of fractures. However, the recognition that mass density is an unsatisfactory predictor of bone strength has, more recently, spurred the search for alternative modalities focusing on 'bone quality,' notably architecture. The P.I. and his co-workers have, during the prior phases of this project, shown theoretically and experimentally that the susceptibility-induced MR signal decay rate (R2') is related to the density and orientation of the trabeculae and that this parameter is able to predict the bone's elastic modulus in vitro. Further, clinical evidence was provided that decreased trabecular bone marrow R2' augments the probability for the occurrence of vertebral fractures and that BMD and R2' jointly improve fracture prediction. The central hypothesis to be tested is that, along with improved methodology and a new MR-based measurement of trabecular bone volume fraction (BVF), a single-modality examination that evaluates both R2' and BVF, better predicts fractures than bone densitometry. We shall examine the above hypothesis by pursuing the aims below; specifically, we shall 1. Further develop and validate improved methodology for acquiring and processing quantitative MR data for measuring R2', conceived during the current cycle of the project. 2. Evaluate a new MR method for measuring cancellous bone volume fraction and assess its relationship to R2' in cancellous bone models and specimens. 3. Measure both R2' and BVF in a cohort of peri- and postmenopausal normal, osteopenic and osteoporotic women and determine the association between the two independently measured parameters and DEXA BMD. 4. Determine the diagnostic accuracy of the techniques of Aims 1 and 2 relative to DEXA BMD z-scores as a means to assess fracture status in the spine in the subjects examined under Aim 3.
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