(Taken from the application): Renal osteodystrophy (ROD) is a multifactorial disorder of bone remodeling, resulting in skeletal deformities and fractures. The histologic spectrum of ROD ranges from markedly increased bone turnover to absent bone turnover. High-turnover disease [osteitis fibrosa (OF)] is caused by secondary hyperparathyroidism, and was once a universal complication of renal failure. OF is characterized by trabecular bone sclerosis and severe cortical thinning. However, the incidence of low-turnover disease [adynamic bone disease (AD)] is now rapidly approaching that of OF. AD is characterized by decreased bone formation and trabecular thinning. The emergence of AD may be due to therapies aimed at preventing OF, such as calcium-containing phosphate binders and active vitamin D sterols. Current studies are focusing on the development of new strategies to prevent OF without suppressing normal bone remodeling. Knowledge of the underlying bone structural abnormalities is essential for developing, selecting and monitoring therapeutic regimens. To date, bone biopsy is the only available tool for characterizing ROD. However, the invasive nature of the procedure has limited its use in clinical care. In addition, bone biopsy is subject to sampling error and provides little information regarding cortical structure and bone's mechanical competence. Non-invasive measures of bone turnover have been disappointing. There is significant overlap in serum PTH levels among patients with AD, OF and normal bone tumover states. Bone densitometric techniques are rarely informative because the projected bone mass represents the integrated sum of the cortical and trabecular components. We hypothesize that a 'virtual bone biopsy' (VBB) based on micro magnetic resonance imaging (u-MRI), in conjunction with image processing, will provide a non-invasive technique to simultaneously assess trabecular structure and cortical thinning. VBB is inherently three-dimensional, is less subject to sampling error, and can be performed repeatedly in longitudinal studies. This pilot project proposes (1) to design and construct a u-MRI coils to assess trabecular structure in the distal tibia; (2) to develop MR-based measures of cortical thickness and cross-sectional area in the tibial diaphysis; and (3) to perform these measures VBB in healthy controls, and in dialysis patients with clinical evidence of extreme high-turnover or low-turnover bone disease. The development of a noninvasive technique to assess cortical and trabecular structure in ROD will facilitate studies of the prevention, treatment and assessment of the biomechanical implications of this prevalent disease.

National Institute of Health (NIH)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Exploratory/Developmental Grants (R21)
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Special Emphasis Panel (ZAR1-AAA-A (M1))
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Mcgowan, Joan A
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University of Pennsylvania
Schools of Medicine
United States
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Gomberg, Bryon R; Saha, Punam K; Wehrli, Felix W (2005) Method for cortical bone structural analysis from magnetic resonance images. Acad Radiol 12:1320-32