The contribution of the pericanalicular matrix to mineral content in human osteonal bone

This is the author accepted manuscript. The final version is available from Elsevier via the DOI in this record.The osteocyte lacunar-canalicular network (LCN) penetrates bone and houses the osteocytes and their processes. Despite its rather low volume fraction, the LCN represents an outstanding large surface that is possibly used by the osteocytes to interact with the surrounding mineralized bone matrix thereby contributing to mineral homeostasis. The aim of this study was to quantitatively describe such contributions by spatially correlating the local density of the LCN with the mineral content at the same location in micrometer-sized volume elements in human osteons. For this purpose, 65 osteons from the femur midshaft from healthy adults (n = 4) and children (n = 2) were structurally characterized with two different techniques. The 3D structure of the LCN in the osteons was imaged with confocal laser scanning microscopy after staining the bone samples with rhodamine. Subsequent image analysis provided the canalicular length density, i.e. the total length of the canaliculi per unit volume (μm/μm3). Quantitative information on the mineral content (wt%Ca) from the identical regions was obtained using quantitative backscattered electron imaging. As the LCN-porosity lowers the mineral content, a negative correlation between Ca content and network density was expected. Calculations predict a reduction of around −0.97 fmol Ca per μm of network. However, the experiment revealed for 62 out of 65 osteons a positive correlation resulting in an average additional Ca loading of +1.15 fmol per μm of canalicular network, i.e. an accumulation of mineral has occurred at dense network regions. We hypothesize that this accumulation happens in the close vicinity of canaliculi forming mineral reservoirs that can be utilized by osteocytes. Significant differences found between individuals indicate that the extent of mineral loading of the reservoir zone reflects an important parameter for mineral homeostasis.German Federal Ministry of Education and ResearchAUVA (Research Funds of the Austrian Workers Compensation Board, Austria)WGKK (Viennese sickness insurance funds, Austria)

Causes of death at very old ages, including for supercentenarians

The causes of death reported on the death certificates of the oldest old are generally seen as unreliable, and as thus providing little useful information on the process leading to death. However, in advanced countries, a majority of the people who die each year are relatively old, and the level of detail provided on medical certificates about the causes of death among this older population is improving. At the same time, scholars are becoming increasingly interested in studying not just the initial cause of death, but multiple causes of death, thereby taking all of the information reported on the certificate into account. This study demonstrates that in a country like France, the cause-of-death pattern evolves regularly until around age 105. The share of people dying of circulatory diseases tends to be quite stable over the age range, while the share of individuals dying of cancer is declining, and the share of people dying of respiratory/infectious diseases is rising. Furthermore, among people who die at very old ages, a typology of multiple causes of death highlights the growing importance of ill-defined causes, while opening the door to an interesting discussion about the concept of cause of death in the supercentenarian population. Instead of representing an ill-defined cause, senility could be considered an actual cause of death. This suggests that daily care is more crucial to the survival of the oldest old than any conventional medical care or treatment. Supercentenarians tend to be so frail that any minor health event or brief lapse of attention on the part of their caregivers can be lethal