The purpose of the Bone Morphometry and Biomechanics Core is to consolidate key personnel and equipment in order to provide a centralized facility that will enhance collaborative and multidisciplinary investigations into the multiple mechanisms that increase bone fragility with age. Core C will perform six procedures in a cost and time efficient manner to facilitate the examination of the changes in bone cell number, architecture, mass, vascularity, and strength in murine models. 1. Undecalcified, plastic embedded, tetracycline labeled sections of vertebral cortical and cancellous bone and femoral diaphyseal cortical bone will be prepared and read histomorphometrically including measurements of the prevalence of osteoblast and osteocyte apoptosis, solute transport from the peripheral circulation to the lacunar-canalicular system as revealed by procion red epifluorescence, and proximity of vascular channels to the tetracycline labeled cancellous perimeter as revealed by the infusion of lead chromate. 2. Frozen sections of bone will be obtained to facilitate quantification of galactosidase activity, immunostaining of targeted cells in transgenic animals and recognition of green fluorescent protein. 3. Micro-CT measurements will be done at necropsy in excised lumbar vertebrae and femora to determine the individual volumetric densitometric contributions of cortical and cancellous bone as well as the 3-dimensional measurements of cortical and cancellous microarchitecture. In addition, the volume and suri'ace area of the vascular system will be measured usingmicro-CT imaging of decalcified bones after perfusion with lead chromate. 4. Bone mass will be determined by dual-energy x-ray absorptiometry. Measurements of the integral density of the global, spinal, and femoral subregions will be performed serially, in longitudinal experiments in live mice. 5. Vertebral compression strength and femoral three-point bending will be measured to determine the significance of the changes in BMD and bone architecture. 6. The Core will train and maintain the continuing education of a key laboratory person from each project to help perform the routine static and dynamic bone histomorphometry.
This work should advance knowledge of how the elderiy develop fractures and ascertain the mechanisms underlying the greater and eariier loss of bone strength than bone mass. Furthermore, these investigations should provide a better understanding of the multiple causes, cortical and cancellous contributions, and optimal management of increased bone fragility that occurs with age.
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