title: The Formation of Calcified Nanospherites during Micropetrosis Represents a Unique Mineralization Mechanism in Aged Human Bone.
abstract: Osteocytes-the central regulators of bone remodeling-are enclosed in a network of microcavities (lacunae) and nanocanals (canaliculi) pervading the mineralized bone. In a hitherto obscure process related to aging and disease, local plugs in the lacuno-canalicular network disrupt cellular communication and impede bone homeostasis. By utilizing a suite of high-resolution imaging and physics-based techniques, it is shown here that the local plugs develop by accumulation and fusion of calcified nanospherites in lacunae and canaliculi (micropetrosis). Two distinctive nanospherites phenotypes are found to originate from different osteocytic elements. A substantial deviation in the spherites' composition in comparison to mineralized bone further suggests a mineralization process unlike regular bone mineralization. Clearly, mineralization of osteocyte lacunae qualifies as a strong marker for degrading bone material quality in skeletal aging. The understanding of micropetrosis may guide future therapeutics toward preserving osteocyte viability to maintain mechanical competence and fracture resistance of bone in elderly individuals.
authors.affiliation: Institute for Osteology and Biomechanics, University Medical Center Hamburg-Eppendorf, Lottestrasse 55a, 22529, Hamburg, Germany.|Laboratory for Anthropology, Institute of Anatomy, Faculty of Medicine, University of Belgrade, Dr Subotica 4/2, 11000, Belgrade, Serbia.
authors.forename: Petar
authors.initials: P
authors.lastname: Milovanovic
authors.affiliation: Institute for Osteology and Biomechanics, University Medical Center Hamburg-Eppendorf, Lottestrasse 55a, 22529, Hamburg, Germany.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Zimmermann
authors.affiliation: Institute for Osteology and Biomechanics, University Medical Center Hamburg-Eppendorf, Lottestrasse 55a, 22529, Hamburg, Germany.
authors.forename: Annika
authors.initials: A
authors.lastname: Vom Scheidt
authors.affiliation: Christiansen Research Group, Max Planck Institute for the Science of Light, Günther-Scharowsky-Str. 1, D-91058, Erlangen, Germany.|Institute of Optics, Information and Photonics, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Staudtstr. 7/B2, 91058, Erlangen, Germany.
authors.forename: Björn
authors.initials: B
authors.lastname: Hoffmann
authors.affiliation: Christiansen Research Group, Max Planck Institute for the Science of Light, Günther-Scharowsky-Str. 1, D-91058, Erlangen, Germany.
authors.forename: George
authors.initials: G
authors.lastname: Sarau
authors.affiliation: Institute for Osteology and Biomechanics, University Medical Center Hamburg-Eppendorf, Lottestrasse 55a, 22529, Hamburg, Germany.
authors.forename: Timur
authors.initials: T
authors.lastname: Yorgan
authors.affiliation: Center of Molecular Neurobiology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, D-20246, Hamburg, Germany.
authors.forename: Michaela
authors.initials: M
authors.lastname: Schweizer
authors.affiliation: Institute for Osteology and Biomechanics, University Medical Center Hamburg-Eppendorf, Lottestrasse 55a, 22529, Hamburg, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Amling
authors.affiliation: Christiansen Research Group, Max Planck Institute for the Science of Light, Günther-Scharowsky-Str. 1, D-91058, Erlangen, Germany.|Institute of Nano-architectures for Energy Conversion, Helmholtz Zentrum Berlin für Materialien und Energie GmbH, Hahn-Meitner-Platz 1, D-14109, Berlin, Germany.|Physics Department, Freie Universität Berlin, Arnimallee 14, 14195, Berlin, Germany.
authors.forename: Silke
authors.initials: S
authors.lastname: Christiansen
authors.affiliation: Institute for Osteology and Biomechanics, University Medical Center Hamburg-Eppendorf, Lottestrasse 55a, 22529, Hamburg, Germany.|Materials Sciences Division, Lawrence Berkeley National Laboratory/University of California-Berkeley, CA, 94720, USA.
authors.forename: Björn
authors.initials: B
authors.lastname: Busse
mesh_terms: D000369:Aged, 80 and over; D000375:Aging / Q000473:pathology*; D001857:Bone Matrix / Q000648:ultrastructure; D001842:Bone and Bones / Q000473:pathology*; D002113:Calcification, Physiologic; D005260:Female; D006801:Humans; D054118:Nanospheres / Q000737:chemistry* / Q000648:ultrastructure; D010011:Osteocytes / Q000648:ultrastructure; D010022:Osteopetrosis / Q000473:pathology*
keywords: biomineralization; bone cells; lacuno-canalicular network; nanospherites; osteocytes