| 1. |
- Hesse, Bernhard, et al.
(author)
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Accessing osteocyte lacunar geometrical properties in human jaw bone on the submicron length scale using synchrotron radiation mu CT
- 2014
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In: Journal of Microscopy. - : Wiley. - 0022-2720 .- 1365-2818. ; 255:3, s. 158-168
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Journal article (peer-reviewed)abstract
- The architectural properties of the osteocyte cell network provide a valuable basis for understanding the mechanisms of bone remodelling, mineral homeostasis, ageing and pathologies. Recent advances in synchrotron microtomography enable unprecedented three-dimensional imaging of both the bone lacunar network and the extracellular matrix. Here, we investigate the three-dimensional morphological properties of osteocyte lacunae in human healthy and bisphosphonate-related osteonecrotic jaw bone based on synchrotron X-ray computed tomography images, with a spatial isotropic voxel size of 300 nm. Bisphosphonate-related osteonecrosis of the jaw is a relatively new disease with increasing incidence, which remains poorly understood. A step forward in elucidating this malady is to assess whether, and how, the morphology of the osteocyte lacunar network is modified in the affected jaw tissue. We evaluate thousands of cell lacunae from five specimens of which three originate from patients diagnosed with bisphosphonate-associated osteonecrosis. In this exploratory study, we report three-dimensional quantitative results on lacunar volumes (296-502 mu m(3)), shape (approximated by an ellipsoidal shape with principal axes a > b > c, such that a = 2.2b and a = 4c) and spatial distribution (i.e., 50% of the mineralized matrix volume is located within 12 mu m to the closest lacunar boundary) at submicron resolution on such specimens. We observe that the average lacunar volumes of the bisphosphonate-related osteonecrotic jaw specimens were within the range of volumes found in the two specimens originating from healthy donors and conclude that lacunar volumes are not the key element in the course of bisphosphonate-related osteonecrotic jaw. In three out of five specimens we observe lacunar volume sizes in segmented osteons to be significantly different compared to lacunar volumes in the adjacent tissue regions. Furthermore, we quantify the number of lacunae containing small dense objects (on average 9%). In contrast to lacunar morphology we report the lacunar density (16 000-50 000 per mm(3)) to be different in jaw bone tissue compared to what has been reported in femoral sites.
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| 2. |
- Hesse, Bernhard, et al.
(author)
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Alterations of Mass Density and 3D Osteocyte Lacunar Properties in Bisphosphonate- Related Osteonecrotic Human Jaw Bone, a Synchrotron mu CT Study
- 2014
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In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:2, s. e88481-
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Journal article (peer-reviewed)abstract
- Osteonecrosis of the jaw, in association with bisphosphonates (BRONJ) used for treating osteoporosis or cancer, is a severe and most often irreversible side effect whose underlying pathophysiological mechanisms remain largely unknown. Osteocytes are involved in bone remodeling and mineralization where they orchestrate the delicate equilibrium between osteoclast and osteoblast activity and through the active process called osteocytic osteolysis. Here, we hypothesized that (i) changes of the mineralized tissue matrix play a substantial role in the pathogenesis of BRONJ, and (ii) the osteocyte lacunar morphology is altered in BRONJ. Synchrotron mu CT with phase contrast is an appropriate tool for assessing both the 3D morphology of the osteocyte lacunae and the bone matrix mass density. Here, we used this technique to investigate the mass density distribution and 3D osteocyte lacunar properties at the sub-micrometer scale in human bone samples from the jaw, femur and tibia. First, we compared healthy human jaw bone to human tibia and femur in order to assess the specific differences and address potential explanations of why the jaw bone is exclusively targeted by the necrosis as a side effect of BP treatment. Second, we investigated the differences between BRONJ and control jaw bone samples to detect potential differences which could aid an improved understanding of the course of BRONJ. We found that the apparent mass density of jaw bone was significantly smaller compared to that of tibia, consistent with a higher bone turnover in the jaw bone. The variance of the lacunar volume distribution was significantly different depending on the anatomical site. The comparison between BRONJ and control jaw specimens revealed no significant increase in mineralization after BP. We found a significant decrease in osteocyte-lacunar density in the BRONJ group compared to the control jaw. Interestingly, the osteocyte-lacunar volume distribution was not altered after BP treatment.
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| 3. |
- Hesse, Bernhard, et al.
(author)
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Canalicular Network Morphology is the Major Determinant of the Spatial Distribution of Mass Density in Human Bone Tissue : Evidence by Means of Synchrotron Radiation Phase-Contrast nano-CT
- 2015
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In: Journal of Bone and Mineral Research. - : Wiley. - 0884-0431 .- 1523-4681. ; 30:2, s. 346-356
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Journal article (peer-reviewed)abstract
- In bone remodeling, maturation of the newly formed osteonal tissue is associated with a rapid primary increase followed by a slower secondary increase of mineralization. This requires supply and precipitation of mineral into the bone matrix. Mineral delivery can occur only from the extracellular fluid via interfaces such as the Haversian system and the osteocyte pore network. We hypothesized that in mineralization, mineral exchange is achieved by the diffusion of mineral from the lacunar-canalicular network (LCN) to the bone matrix, resulting in a gradual change in tissue mineralization with respect to the distance from the pore-matrix interface. We expected to observe alterations in the mass density distribution with tissue age. We further hypothesized that mineral exchange occurs not only at the lacunar but also at the canalicular boundaries. The aim of this study was, therefore, to investigate the spatial distribution of mass density in the perilacunar and pericanalicular bone matrix and to explore how these densities are influenced by tissue aging. This is achieved by analyzing human jawbone specimens originating from four healthy donors and four treated with high-dosage bisphosphonate using synchrotron radiation phase-contrast nano-CT with a 50-nm voxel size. Our results provide the first experimental evidence that mass density in the direct vicinity of both lacunae (p<0.001) and canaliculi (p<0.001) is different from the mean matrix mass density, resulting in gradients with respect to the distance from both pore-matrix interfaces, which diminish with increasing tissue age. Though limited by the sample size, these findings support our hypotheses. Moreover, the density gradients are more pronounced around the lacunae than around the canaliculi, which are explained by geometrical considerations in the LCN morphology. In addition, we speculate that mineral exchange occurs at all interfaces of the LCN, not only in mineralization but also in mineral homeostasis.
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| 4. |
- Hoffmann, Sabine, et al.
(author)
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A Research Agenda for the Future of Urban Water Management : Exploring the Potential of Nongrid, Small-Grid, and Hybrid Solutions
- 2020
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In: Environmental Science and Technology. - : American Chemical Society (ACS). - 0013-936X .- 1520-5851. ; 54:9, s. 5312-5322
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Research review (peer-reviewed)abstract
- Recent developments in high- and middle-income countries have exhibited a shift from conventional urban water systems to alternative solutions that are more diverse in source separation, decentralization, and modularization. These solutions include nongrid, small-grid, and hybrid systems to address such pressing global challenges as climate change, eutrophication, and rapid urbanization. They close loops, recover valuable resources, and adapt quickly to changing boundary conditions such as population size. Moving to such alternative solutions requires both technical and social innovations to coevolve over time into integrated socio-technical urban water systems. Current implementations of alternative systems in high- and middle-income countries are promising, but they also underline the need for research questions to be addressed from technical, social, and transformative perspectives. Future research should pursue a transdisciplinary research approach to generating evidence through socio-technical "lighthouse" projects that apply alternative urban water systems at scale. Such research should leverage experiences from these projects in diverse socio-economic contexts, identify their potentials and limitations from an integrated perspective, and share their successes and failures across the urban water sector.
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