David L. Haupt

Early Estrogen Replacement Therapy Reverses the Rapid Loss of Trabecular Bone Volume and Prevents Further Deterioration of Connectivity in the Rat

To evaluate the ability of estrogen replacement therapy (ERT) to prevent changes in trabecular bone volume (BV/TV) and connectivity beginning either at ovariectomy (OVX) or 5–13 days after OVX in adult female rats, the right proximal tibial was examined by three‐dimensional X‐ray tomographic microscopy (XTM) in vivo. Animals had XTM scans of the right tibia and then were randomized into six groups (n = 9). Groups 2–6 had bilateral (OVX), while group 1 was sham‐ovariectomized (OVXd) on day 0. Animals were treated with vehicle (groups 1 and 2) or 17β‐estradiol therapy (ERT) at 10 μ g/kg three times per week starting at days 0, 5, 8, and 13 post‐OVX (groups 3, 4, 5, and 6), until day 50 when they were rescanned by XTM and sacrificed. Trabecular bone structural variables were calculated from XTM data (BV/TVx and β1/BV/TVx) and standard histomorphometry. Trabecular bone volume (BV/TVx) and the trabecular connections per cubic millimeter of trabecular bone (β1/BV/TVx) were maintained in both sham‐OVXd animals and OVX animals given ERT from the time of OVX. However, OVX + vehicle–treated animals lost 54% BV/TVx and 46% β1/BV/TVx (p < 0.01 from day 0). BV/TVx and β1/BV/TVx decreased rapidly post‐OVX to −22% and −25% at day 13 (p < 0.01 from day 0). ERT initiated at day 5, 8, and 13 post‐OVX restored BV/TVx to baseline values at day 50 by modestly increasing trabecular plate thickness; however, β1/BV/TVx was reduced in all OVX groups when compared with their baseline values. ERT also caused a significant reduction in bone turnover compared with OVX + vehicle; however, resorption was suppressed more than formation. These results demonstrate that ERT can restore the lost trabecular bone, but not trabecular connectivity, that occurs soon after OVX by allowing bone formation to continue in previously activated bone remodeling units while suppressing the production of new remodeling units. This may be the mechanism by which prompt intervention with estrogen and other antiresorptive agents can restore bone mass that has been lost from the increase in remodeling space, and thereby reduce the risk of osteoporotic fractures in postmenopausal women.

Acute Changes in Trabecular Bone Connectivity and Osteoclast Activity in the Ovariectomized Rat In Vivo

Estrogen deficiency results in a loss of trabecular bone mass and structure that leads to an increased incidence of osteoporotic fractures. The purpose of this study was to determine the time course for trabecular structure deterioration and changes in bone turnover just after ovariectomy in the rat. Six‐month‐old female virgin Sprague‐Dawley rats had their right proximal tibia scanned by X‐ray tomographic microscopy (XTM) at baseline (day 0). Animals were then randomized into two groups, and in each group 9 were sham‐operated and 11 were ovariectomized and had repeat XTM scans on days 5, 13, 29, and 42 postovariectomy in group 1 and on days 8, 13, 33, and 50 postovariectomy in group 2. Urine was collected for deoxypyridinoline (DPD) cross‐link measurements 24 h before each XTM scan and analyzed by ELISA. Trabecular bone structural variables and bone turnover endpoints were calculated from XTM data and standard histomorphometry. Trabecular connectivity decreased 27% by days 5 and 8 postovariectomy (p < 0.01) and continued to decrease up to day 50 postovariectomy (p < 0.01). The trabecular bone volume decreased 25% by 8 days postovariectomy (p < 0.01), and it continued to decrease through day 50. DPD cross‐link excretion had increased 37% on day 13 (p < 0.01) and by over 100% of baseline by day 50 postovariectomy. Trabecular bone connectivity and volume deteriorate rapidly while DPD cross‐link excretion increased more slowly in acute estrogen deficiency. These data suggest that if an agent is to preserve fully trabecular bone structure, it must be instituted very early in the estrogen‐deficient state. They also suggest that a lag time exists before DPD excretion properly mirrors newly induced conditions of high bone turnover in this rat model.

Nature of damage in fused silica induced by high-fluence 3-omega 355-nm laser pulses, a multiscale morphology microstructure, and defect chemistry study

The morphology and microstructure of damage sites in high quality fused silica induced by high power UV (355 nm) laser light have been investigated using a suite of microscopic and spectroscopic tools. These include SEM, TEM, microprobe analysis, XPS, SIMS and x-ray micro-tomography utilizing intense synchrotron radiation. Systematic SEM examinations show that the damage sites consist primarily of a molten core region (thermal explosion), surrounded by a near concentric region of fractured material. The latter arises from propagation of lateral cracks induced by the laser- generated shock waves. The size of the overall crater is dependent of the laser fluence, number of pulses, damage history and environment. In particular, differences in morphology of the damage sites are identified: air vs. vacuum; exit (more severe) surface vs. entrance surface; and regular polish (more severe) vs. super polish surfaces. A compaction layer, approximately 10 microns thick and approximately 20% higher in density has been identified with x-ray tomography. This layer has further been substantiated by micro-Raman spectroscopy. High resolution microprobe analysis shows that there is no variation in the Si/O stoichiometry of silica in the compaction layer to within +/- 1.6%. High resolution TEM indicates the absence of crystalline nano-particles of Si in the compaction layer. Macro- (10-0.1 micrometers ) and micro-cracks (200-20 nm) are found, however, in the bright field images. The Si 2p XPS spectra indicates that there is a lower Si3+ species on at least the top 2-3 nm of the compaction layer. These findings are critical to the design of a knowledge-based mitigation process for laser damage growth.

Applications of synchrotron microtomography in osteoporosis research

Synchrotron microtomography enables us to visualize trabecular bone microarchitecture in 3D with a spatial resolution of a few microns. With recent developments in finite element modeling, it is possible to incorporate these images voxel by voxel into a finite-element model of the elastic properties of the bone. The ability to calculate mechanical behavior from 3D images will help us to understand the relationships between bone structure and properties.

X-ray tomographic microscopy investigation of the ductile rupture of an aluminum foil bonded between sapphire blocks

Metal/ceramic interfaces play a critical role in determining the mechanical behavior of composite materials. In metal-matrix composites (MMCs), the presence of the reinforcing phase places the normally ductile matrix phase in a highly constrained state of stress. Strong interfaces between matrix and reinforcement favor crack advance by ductile rupture of the metal, while weak interfaces favor debonding. In practice, the introduction of reinforcements into a metal produces a variability in behavior that limits its commercial application. Because of this, micromechanics models of failure have been developed for these systems that attempt to describe the failure mechanisms. The authors have experimentally duplicated the simplified geometry of the micromechanics models and subjected the specimens to a well defined stress state in bending. The bend tests were interrupted and XTM was performed to reveal the mechanism of crack extension.

Three-Dimensional, Nondestructive Imaging of Low Density Materials

The goal of this study was to develop a three-dimensional imaging method for studies of deformation in low-density materials during loading, and to implement finite element solutions of the elastic equations based on the images. Specimens of silica-reinforced polysiloxane foam pads, 15 mm in diameter by 1 mm thick, were used for this study. The nominal pore density was 50%, and the pores approximated interconnected spheres. The specimens were imaged with microtomography at {approx}16{micro}m resolution. A rotating stage with micrometer driven compression allowed imaging of the foams during deformation with precise registration of the images. A finite element mesh, generated from the image voxels, was used to calculate the mechanical properties of the structure, and the results were compared with conventional mechanical testing. The foam exhibited significant nonlinear behavior with compressive loading. The finite-element calculations from the images, which were in excellent agreement with experimental data, suggested that nonlinear behavior in the load displacement curves arises from buckling of the cell walls during compression and not from any nonlinear properties of the base elastomer. High-resolution microtomography, coupled with efficient finite-element modeling, shows promise for improving our understanding of the deformation behavior of cellular materials.

Mechanism of ductile rupture in the Al/sapphire system elucidated using x-ray tomographic microscopy

The fracture of a thin metal foil constrained between alumina or sapphire blocks has been studied by a number of investigators. The systems that have been investigated include Al, Au, Nb, and Cu. Except for Al/Al{sub 2}O{sub 3} interfaces, these systems exhibit a common fracture mechanism: pores form at the metal/ceramic interface several foil thicknesses ahead of the crack which, under increasing load, grow and link with the initial crack. This mechanism leaves metal o none side of the fracture surface and clean ceramic on the other. This has not been the observation in Al/Al{sub 2}O{sub 3} bonds where at appropriate thicknesses of Al, the fracture appears to proceed as a ductile rupture through the metal. This paper addresses the question of why the fracture of the Al/Al{sub 2}O{sub 3} system appears to be different from other systems by probing the fracture mechanism using X-ray tomographic microscopy (XTM). The authors have experimentally duplicated the simplified geometry of the micromechanics models and subjected the specimens to a well defined stress state in bending. The bend tests were interrupted and XTM was performed to reveal the mechanism of crack extension.