Recent studies have demonstrated matrix-mineral alterations in bone tissue surrounding osteocytes in estrogen-deficient animals. While cortical bone porosity has been shown to be a contributor to the mechanical properties of bone tissue, little analysis has been done to investigate the effects of estrogen deficiency on bone's microporosities, including the vascular and osteocyte lacunar porosities. In this study we examined alterations in cortical bone microporosity, mineralization, and cancellous bone architecture due to estrogen deficiency in the ovariectomized rat model of postmenopausal osteoporosis. Twenty-week-old female Sprague-Dawley rats were subjected to either ovariectomy or sham surgery. Six weeks post-surgery tibiae were analyzed using high-resolution micro-CT, backscattered electron imaging, nanoindentation, and dynamic histomorphometry. Estrogen deficiency caused an increase in cortical bone vascular porosity, with enlarged vascular pores and little change in tissue mineral density in the proximal tibial metaphysis. Measurements of cancellous architecture corresponded to previous studies reporting a decrease in bone volume fraction, an increase in trabecular separation, and a decrease in trabecular number in the proximal tibia due to estrogen deficiency. Nanoindentation results showed no differences in matrix stiffness in osteocyte-rich areas of the proximal tibia of estrogen-deficient rats, and bone labeling and backscattered electron imaging showed no significant changes in mineralization around the vascular pores. The findings demonstrate local surface alterations of vascular pores due to estrogen deficiency. An increase in cortical vascular porosity may diminish bone strength as well as alter bone mechanotransduction via interstitial fluid flow, both of which could contribute to bone fragility during postmenopausal osteoporosis.

Loading-induced interstitial fluid flow in the microporosities of bone is critical for osteocyte mechanotransduction and for the maintenance of tissue health, enhancing convective transport in the lacunar-canalicular system. In recent studies, our group has reported alterations of bone's vascular porosity and lacunar-canalicular system microarchitecture in a rat model of postmenopausal osteoporosis. In this work, poroelastic finite element analysis was used to investigate whether these microstructural changes can affect interstitial fluid flow around osteocytes. Animal-specific finite element models were developed combining micro-CT reconstructions of bone microstructure and measures of the poroelastic material properties. These models were used to quantify and compare loading-induced fluid flow in the lacunar-canalicular system of ovariectomized and sham-operated rats. A parametric analysis was also used to quantify the influence of the lacunar-canalicular permeability and vascular porosity on the fluid velocity magnitude. Results show that mechanically-induced interstitial fluid velocity can be significantly reduced in the lacunar-canalicular system of ovariectomized rats. Interestingly, the vascular porosity is shown to have a major influence on interstitial fluid flow, while the lacunar-canalicular permeability influence is limited when larger than 10m. Altogether our results suggest that microstructural changes associated with the osteoporotic condition can negatively affect interstitial fluid flow around osteocytes in the lacunar-canalicular system of cortical bone. This fluid flow reduction could impair mechanosensation of the osteocytic network, possibly playing a role in the initiation and progression of age-related bone loss and postmenopausal osteoporosis.

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Pulse Wave Imaging (PWI) is a non-invasive, ultrasound-based technique, which provides information on arterial wall stiffness by estimating the Pulse Wave Velocity (PWV) along an imaged arterial wall segment. The aims of the present study were to: 1) utilize the PWI information to automatically and optimally divide the artery into the segments with most homogeneous properties and 2) assess the feasibility of this method to provide arterial wall mechanical characterization in normal and atherosclerotic carotid arteries in vivo. A silicone phantom consisting of a soft and stiff segment along its longitudinal axis was scanned at the stiffness transition, and the PWV in each segment was estimated through static testing. The proposed algorithm detected the stiffness interface with an average error of 0.98±0.49 mm and 1.04±0.27 mm in the soft-to-stiff and stiff-to-soft pulse wave transmission direction, respectively. Mean PWVs estimated in the case of the soft-to-stiff pulse wave transmission direction were 2.47±0.04m/sec and 3.43±0.08 m/sec for soft and stiff phantom segments, respectively, while in the case of stiff-to-soft transmission direction PWVs were 2.60±0.18 m/sec and 3.72±0.08m/sec for the soft and stiff phantom segments, respectively, which were in good agreement with the PWVs obtained through static testing (soft segment: 2.41 m/sec, stiff segment: 3.52 m/sec). Furthermore, the carotid arteries of N=9 young subjects (22-32 y.o.) and N=9 elderly subjects (60-73 y.o.) with no prior history of carotid artery disease were scanned, in vivo, as well as the atherosclerotic carotid arteries of N=12 (59-85 y.o.) carotid artery disease patients. One-way ANOVA with Holm-Sidak correction showed that the number of most homogeneous segments in which the artery was divided was significantly higher in the case of carotid artery disease patients compared to young (3.25±0.86 segments vs 1.00±0.00 segments, p-value<0.0001) and elderly non-atherosclerotic subjects (3.25±0.86 segments vs 1.44±0.51 segments p-value<0.0001), indicating increased wall inhomogeneity in atherosclerotic arteries. The compliance provided by the proposed algorithm was significantly higher in non-calcified/high-lipid plaques as compared

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