title: Spatial heterogeneity in the canalicular density of the osteocyte network in human osteons.
abstract: Osteocytes interconnect with each other forming an intricate cell network within the mineralized bone matrix. One important function of the osteocyte network is the mechano-regulation of bone remodeling, where a possible mechanism includes the fluid flow through the porosity housing the cell network - the osteocyte lacuno-canalicular network (OLCN). In our study the OLCN in human osteons was three-dimensionally imaged with the aim to obtain a quantitative description of the canalicular density and spatial variations of this quantity within osteons. The topology of the OLCN was determined by first staining the bone samples with rhodamine, then imaging the OLCN with confocal laser scanning microscopy and finally using image analysis to obtain a skeletonized version of the network for further analysis. In total 49 osteons were studied from the femoral cortical bone of four different middle-aged healthy women. The mean canalicular density given as length of the canaliculi in a unit volume was 0.074 ± 0.015 μm/μm3(corresponding to 74 km/cm3). No correlation was found between the canalicular density and neither the size of the osteon nor the volume fraction occupied by osteocyte lacunae. Within osteons the canalicular density varied substantially with larger regions without any network. On average the canalicular density decreases when moving from the Haversian canal outwards towards the cement line. We hypothesize that a decrease in accessible canaliculi with tissue age as a result of micropetrosis can reduce the local mechanosensitivity of the bone. Systematic future studies on age- and disease-related changes on the topology of the OLCN have to demonstrate the diagnostic potential of the presented characterization method.
authors.affiliation: Max Planck Institute of Colloids and Interfaces, Department of Biomaterials, D-14424 Potsdam, Germany.
authors.forename: Felix
authors.initials: F
authors.lastname: Repp
authors.affiliation: Max Planck Institute of Colloids and Interfaces, Department of Biomaterials, D-14424 Potsdam, Germany; ETH Zürich, Laboratory of Applied Mechanobiology, Department of Health Sciences and Technology, CH-8093 Zurich, Switzerland.
authors.forename: Philip
authors.initials: P
authors.lastname: Kollmannsberger
authors.affiliation: Max Planck Institute of Colloids and Interfaces, Department of Biomaterials, D-14424 Potsdam, Germany; Ludwig Boltzmann Institute of Osteology at Hanusch Hospital of WGKK and AUVA Trauma Centre Meidling, 1st Med. Dept. Hanusch Hospital, A-1140 Vienna, Austria.
authors.forename: Andreas
authors.initials: A
authors.lastname: Roschger
authors.affiliation: Weizmann Institute of Science, Department of Structural Biology, 76100 Rehovot, Israel.
authors.forename: Michael
authors.initials: M
authors.lastname: Kerschnitzki
authors.affiliation: Department of Forensic Medicine, Medical University of Vienna, Sensengasse 2, A-1090 Vienna, Austria.
authors.forename: Andrea
authors.initials: A
authors.lastname: Berzlanovich
authors.affiliation: Department of Anatomy, Center for Anatomy and Cell Biology, Medical University of Vienna, Währinger Straße 13, A-1090 Vienna, Austria.
authors.forename: Gerlinde M
authors.initials: GM
authors.lastname: Gruber
authors.affiliation: Ludwig Boltzmann Institute of Osteology at Hanusch Hospital of WGKK and AUVA Trauma Centre Meidling, 1st Med. Dept. Hanusch Hospital, A-1140 Vienna, Austria.
authors.forename: Paul
authors.initials: P
authors.lastname: Roschger
authors.affiliation: Max Planck Institute of Colloids and Interfaces, Department of Biomaterials, D-14424 Potsdam, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Wagermaier
authors.affiliation: Max Planck Institute of Colloids and Interfaces, Department of Biomaterials, D-14424 Potsdam, Germany.
authors.forename: Richard
authors.initials: R
authors.lastname: Weinkamer
keywords: Canalicular density; Confocal microscopy; Mechano-regulation; Micropetrosis; Network analysis; Osteocyte network