DEVELOPMENT AND REMODELING OF BONE USING EXPERIMENTAL LOADING

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The broad objectives of this project are to examine and differentiate key structure parameters of the mouse femur that change during conditions of differential loading and are responsible for a change in the ultimate breaking strength of the femur. Preliminary results indicate that developing mouse femora when exposed to two types of increased functional loading for 30 days responded by increasing the ultimate breaking strength by up to 74% by changing predictable structural features. However, the structural feature, that were changed to achieve this increased breaking strength were not the same for each experimental treatment. The specific aims of this study are to 1) Correlate the specific structural and mineral density changes with the stimulus that elicited the response. 2) Correlate the structural and mineral density changes with the related increase in breaking strength. 3) Determine if the structural changes seen in mice exposed to differential functional and experimental loading are consistent and long lasting among age groups, from developing to adult mice. Two working hypotheses are proposed: 1) chronic bending moments of moderate intensity elicit structural changes in the femur that mainly increase cortical cross-sectional area and rotational moment of inertia, and 2) short duration high intensity bending moments elicit changes in trabecular architecture and rotational moment of inertia but no changes in cortical cross- sectional area. Mice will be divided into three functional treatment groups: normal exercise control (NE) short duration hypergravity (4G), and chronic burrowing (high litter cage) (HL). Treatments will last for 30 days and will be initiated on day 14, 60 or 518 of age. Experiments will run from 44 to 548 days. A second experimental phase will use pure bending moments of known magnitudes delivered by a stress machine. Applied stresses will be of two types: short duration high intensity, and longer duration low intensity. Undecalcified femora will be sectioned and examined under the scanning electron microscope for cross- sectional area and rotational moment of inertia. Serial cross sections of undecalcified femora will be used to reconstruct the three dimensional architecture of trabecular bone. Cortical and trabecular bone d:ta will be quantified with the aid of a visual analysis system. Mounted sectioned and ground undecalcified femora will be used for X-ray micro-analysis determinations of calcium and phosphorus densities. Prepared femora will be tested for ultimate breaking strength with an Instron Materials Tester. Results of this study may have application to the development of structurally sound bones in children and the remodeling of bone in the osteoporotic elderly.