TOXIC FACTORS AFFECTING BONE QUALITY DURING GROWTH

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The proposed research focuses on the effect environmental toxins on the material properties of bone during growth. Changes in the macromolecular composition and organization of bone tissue due to toxic substances will be related to alteration in gross architecture of bone. The study will contribute to a general theory of bone properties which will aid in the prevention and treatment of bone disease. Bone of sufficient quality is essential to preventing or forestalling the onset and/or reducing the severity of common adult bone diseases like osteoporosis and osteoarthritis. The ubiquity of environmental toxins make it imperative to understand how bone density, stiffness, collagen fibril structure and the spatial arrangement of bone in cross-section can be affected by these substances. Growing bone is particularly sensitive to environmental insults and reduced bone tissue quality early in life may lead to increased risk of bone disease in adults. It is therefore important to understand the mechanism(s) which control mineralization and elastic properties of bone during growth. Elastic properties, dimensional change with water content, composition, density, neutron diffraction, cross-linking density, and cross-sectional geometric properties are measure to characterize normal and pathological bone at different stages of growth. Bone pathologies are induced under well-controlled conditions by dietary means using beta-aminopropionitrile - - a toxic derivative of the sweet pea, cycads -- a tropical food source containing lethal toxins, and fluoride. Data from physical measurements of the tissue will be combined with data from morphometric and histomorphometric analyses for a comprehensive evaluation of bone pathology induced by toxic substances.