title: Nano-structural, compositional and micro-architectural signs of cortical bone fragility at the superolateral femoral neck in elderly hip fracture patients vs. healthy aged controls.
abstract: To unravel the origins of decreased bone strength in the superolateral femoral neck, we assessed bone structural features across multiple length scales at this cortical fracture initiating region in postmenopausal women with hip fracture and in aged-matched controls. Our combined methodological approach encompassed atomic force microscopy (AFM) characterization of cortical bone nano-structure, assessment of mineral content/distribution via quantitative backscattered electron imaging (qBEI), measurement of bone material properties by reference point indentation, as well as evaluation of cortical micro-architecture and osteocyte lacunar density. Our findings revealed a wide range of differences between the fracture group and the controls, suggesting a number of detrimental changes at various levels of cortical bone hierarchical organization that may render bone fragile. Namely, mineral crystals at external cortical bone surfaces of the fracture group were larger (65.22nm±41.21nm vs. 36.75nm±18.49nm, p<0.001), and a shift to a higher mineral content and more homogenous mineralization profile as revealed via qBEI were found in the bone matrix of the fracture group. Fracture cases showed nearly 35% higher cortical porosity and showed significantly reduced osteocyte lacunar density compared to controls (226±27 vs. 247±32#/mm(2), p=0.05). Along with increased crystal size, a shift towards higher mineralization and a tendency to increased cortical porosity and reduced osteocyte lacunar number delineate that cortical bone of the superolateral femoral neck bears distinct signs of fragility at various levels of its structural organization. These results contribute to the understanding of hierarchical bone structure changes in age-related fragility.
authors.affiliation: Laboratory for Anthropology, Institute of Anatomy, School of Medicine, University of Belgrade, 4/2 Dr Subotica, 11000 Belgrade, Serbia; Department of Osteology & Biomechanics, University Medical Center Hamburg-Eppendorf, 59 Lottestr., D-22529 Hamburg, Germany. Electronic address: drpmilovanovic@gmail.com.
authors.forename: Petar
authors.initials: P
authors.lastname: Milovanovic
authors.affiliation: Laboratory for Atomic Physics, Institute of Nuclear Sciences Vinca, University of Belgrade, 11001 Belgrade, Serbia. Electronic address: zlatkora@vinca.rs.
authors.forename: Zlatko
authors.initials: Z
authors.lastname: Rakocevic
authors.affiliation: Laboratory for Anthropology, Institute of Anatomy, School of Medicine, University of Belgrade, 4/2 Dr Subotica, 11000 Belgrade, Serbia. Electronic address: ddjonic@yahoo.com.
authors.forename: Danijela
authors.initials: D
authors.lastname: Djonic
authors.affiliation: Institute of Forensic Medicine, School of Medicine, University of Belgrade, 31a Deligradska, 11000 Belgrade, Serbia. Electronic address: vladinmejl@yahoo.com.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Zivkovic
authors.affiliation: Department of Osteology & Biomechanics, University Medical Center Hamburg-Eppendorf, 59 Lottestr., D-22529 Hamburg, Germany. Electronic address: hahn@uke.de.
authors.forename: Michael
authors.initials: M
authors.lastname: Hahn
authors.affiliation: Institute of Forensic Medicine, School of Medicine, University of Belgrade, 31a Deligradska, 11000 Belgrade, Serbia. Electronic address: bobanvladislav@yahoo.com.
authors.forename: Slobodan
authors.initials: S
authors.lastname: Nikolic
authors.affiliation: Department of Osteology & Biomechanics, University Medical Center Hamburg-Eppendorf, 59 Lottestr., D-22529 Hamburg, Germany. Electronic address: amling@uke.de.
authors.forename: Michael
authors.initials: M
authors.lastname: Amling
authors.affiliation: Department of Osteology & Biomechanics, University Medical Center Hamburg-Eppendorf, 59 Lottestr., D-22529 Hamburg, Germany. Electronic address: b.busse@uke.uni-hamburg.de.
authors.forename: Bjoern
authors.initials: B
authors.lastname: Busse
authors.affiliation: Laboratory for Anthropology, Institute of Anatomy, School of Medicine, University of Belgrade, 4/2 Dr Subotica, 11000 Belgrade, Serbia. Electronic address: marijadjuric5@gmail.com.
authors.forename: Marija
authors.initials: M
authors.lastname: Djuric
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001696:Biomechanical Phenomena; D015519:Bone Density / Q000502:physiology; D002118:Calcium / Q000032:analysis; D016022:Case-Control Studies; D003460:Crystallization; D005260:Female; D005272:Femur Neck / Q000737:chemistry / Q000503:physiopathology / Q000648:ultrastructure*; D006620:Hip Fractures / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D006801:Humans; D018625:Microscopy, Atomic Force / Q000379:methods; D010011:Osteocytes / Q000473:pathology; D015663:Osteoporosis, Postmenopausal / Q000473:pathology / Q000503:physiopathology; D058866:Osteoporotic Fractures / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D055114:X-Ray Microtomography / Q000379:methods
chemical_list: D002118:Calcium
keywords: Aging; Atomic force microscopy; Bone fragility; Hierarchical structure; Hip fracture; Quantitative backscatter electron microscopy