Influence of the ultrastructure on the fracture characteristics of human bone in physiological and pathological conditions
Final Report Abstract
Aging and bone diseases are associated with an increased risk of fracture. Therefore, it is important to understand the origins of such disease-related deterioration in bone's mechanical properties. The mechanical integrity of bone derives from its hierarchical structure, which in healthy states is able to resist bone fracture and tolerate damage. Indeed, the mechanisms through which bone derives its mechanical properties are related to bone quality parameters. Comprehensive bone quality assessment in healthy and diseased cases was carried out to provide new data on bone's cellular activities, structural changes and mechanical resistance. In this context, we have used an integrated approach combining experimental bone quality assessment tools and clinical medical technology by using high resolution peripheral quantitative microcomputed tomography (HR-pQCT), dual energy x-ray absorptiometry (DXA), microcomputed tomography, bone histomorphometry, synchrotron small-angle X-ray scattering (SAXS) / wide-angle X-ray diffraction (WAXD), backscattered electron imaging (BSE), microanalysis (EDX, µXRF), reference point indentation/nanoindentation, Raman and Fourier Transform Infrared spectroscopy (FTIR). Although healthy bone tissue can generally resist physiological loading environments, certain conditions such as aging and disease can significantly increase the risk of fracture in patients. Specifically, the reduced mechanical integrity originates from various alterations to the hierarchical structure of bone tissue. With this program, we have analyzed how human bone structure resists fracture in healthy bone and how changes to the bone structure due to aging, osteoporosis, osteoporosis treatment and changed collagen matrix properties can affect the mechanical integrity of bone tissue.
Publications
- Osteocytic canalicular networks: morphological implications for altered mechanosensitivity. ACS Nano. 2013 Sep 24;7(9):7542-51
Milovanovic P, Zimmermann EA, Hahn M, Djonic D, Püschel K, Djuric M, Amling M, Busse B
(See online at https://doi.org/10.1021/nn401360u) - Effects of long-term alendronate treatment on bone mineralisation, resorption parameters and biomechanics of single human vertebral trabeculae. Eur Cell Mater. 2014 Sep 22;28:152-63
Krause M, Soltau M, Zimmermann EA, Hahn M, Kornet J, Hapfelmeier A, Breer S, Morlock M, Wulff B, Püschel K, Glueer CC, Amling M, Busse B
(See online at https://doi.org/10.22203/eCM.v028a12) - Fracture resistance of human cortical bone across multiple length-scales at physiological strain rates. Biomaterials. 2014 Jul;35(21):5472-81
Zimmermann EA, Gludovatz B, Schaible E, Busse B, Ritchie RO
(See online at https://doi.org/10.1016/j.biomaterials.2014.03.066) - Multi-level characterization of human femoral cortices and their underlying osteocyte network reveal trends in quality of young, aged, osteoporotic and antiresorptive-treated bone. Biomaterials. 2015 Mar;45:46-55
Milovanovic P, Zimmermann EA, Riedel C, vom Scheidt A, Herzog L, Krause M, Djonic D, Djuric M, Püschel K, Amling M, Ritchie RO, Busse B
(See online at https://doi.org/10.1016/j.biomaterials.2014.12.024) - Intrinsic mechanical behavior of femoral cortical bone in young, osteoporotic and bisphosphonate-treated individuals in low- and high energy fracture conditions. Sci Rep. 2016 Feb 16;6:21072
Zimmermann EA, Schaible E, Gludovatz B, Schmidt FN, Riedel C, Krause M, Vettorazzi E, Acevedo C, Hahn M, Püschel K, Tang S, Amling M, Ritchie RO, Busse B
(See online at https://doi.org/10.1038/srep21072) - Assessment of collagen quality associated with non-enzymatic cross-links in human bone using Fourier-transform infrared imaging. Bone. 2017 Apr;97:243-251
Schmidt FN, Zimmermann EA, Campbell GM, Sroga GE, Püschel K, Amling M, Tang SY, Vashishth D, Busse B
(See online at https://doi.org/10.1016/j.bone.2017.01.015) - Atypical fracture with long-term bisphosphonate therapy is associated with altered cortical composition and reduced fracture resistance. Proc Natl Acad Sci USA. 2017 Aug 15;114(33):8722-8727
Lloyd AA, Gludovatz B, Riedel C, Luengo EA, Saiyed R, Marty E, Lorich DG, Lane JM, Ritchie RO, Busse B, Donnelly E
(See online at https://doi.org/10.1073/pnas.1704460114) - The Formation of Calcified Nanospherites during Micropetrosis Represents a Unique Mineralization Mechanism in Aged Human Bone. Small. 2017 Jan;13(3)
Milovanovic P, Zimmermann EA, Vom Scheidt A, Hoffmann B, Sarau G, Yorgan T, Schweizer M, Amling M, Christiansen S, Busse B
(See online at https://doi.org/10.1002/smll.201602215) - Bone tissue aging affects mineralization of cement lines. Bone. 2018 May;110:187-193
Milovanovic P, Vom Scheidt A, Mletzko K, Sarau G, Püschel K, Djuric M, Amling M, Christiansen S, Busse B
(See online at https://doi.org/10.1016/j.bone.2018.02.004) - Inter-site variability of the osteocyte lacunar network in the cortical bone underpins fracture susceptibility of the superolateral femoral neck. Bone. 2018 Jul;112:187-193
Rolvien T, Vom Scheidt A, Stockhausen KE, Milovanovic P, Djonic D, Hubert J, Hawellek T, Wacker A, Jebens V, Püschel K, Zimmermann EA, Djuric M, Amling M, Busse B
(See online at https://doi.org/10.1016/j.bone.2018.04.018)
