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Title: Mechanical Competence and Bone Quality Develop During Skeletal Growth

Abstract

Bone fracture risk is influenced by bone quality, which encompasses bone's composition as well as its multiscale organization and architecture. Aging and disease deteriorate bone quality, leading to reduced mechanical properties and higher fracture incidence. Largely unexplored is how bone quality and mechanical competence progress during longitudinal bone growth. In this study, human femoral cortical bone was acquired from fetal (n = 1), infantile (n = 3), and 2- to 14-year-old cases (n = 4) at the mid-diaphysis. Bone quality was assessed in terms of bone structure, osteocyte characteristics, mineralization, and collagen orientation. The mechanical properties were investigated by measuring tensile deformation at multiple length scales via synchrotron X-ray diffraction. We find dramatic differences in mechanical resistance with age. Specifically, cortical bone in 2- to 14-year-old cases exhibits a 160% greater stiffness and 83% higher strength than fetal/infantile cases. The higher mechanical resistance of the 2- to 14-year-old cases is associated with advantageous bone quality, specifically higher bone volume fraction, better micronscale organization (woven versus lamellar), and higher mean mineralization compared with fetal/infantile cases. Our study reveals that bone quality is superior after remodeling/modeling processes convert the primary woven bone structure to lamellar bone. In this cohort of female children,more » the microstructural differences at the femoral diaphysis were apparent between the 1- to 2-year-old cases. Indeed, the lamellar bone in 2- to 14-year-old cases had a superior structural organization (collagen and osteocyte characteristics) and composition for resisting deformation and fracture than fetal/infantile bone. Mechanistically, the changes in bone quality during longitudinal bone growth lead to higher fracture resistance because collagen fibrils are better aligned to resist tensile forces, while elevated mean mineralization reinforces the collagen scaffold. Thus, our results reveal inherent weaknesses of the fetal/infantile skeleton signifying its inferior bone quality. These results have implications for pediatric fracture risk, as bone produced at ossification centers during children's longitudinal bone growth could display similarly weak points.« less

Authors:
 [1];  [1];  [1];  [1];  [2];  [3];  [4];  [5];  [2];  [6]; ORCiD logo [1];  [7]; ORCiD logo [1]
  1. Univ. Medical Center, Hamburg (Germany). Dept. of Osteology and Biomechancis
  2. European Synchrotron Radiation Facility (ESRF), Grenoble (France). Beamline ID 10
  3. Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Advanced Light Source (ALS), Experimental Systems Group
  4. Univ. of New South Wales (UNSW), Sydney, NSW (Australia). School of Mechanical and Manufacturing Engineering
  5. Univ. Medical Center, Hamburg (Germany). Dept. of Medical Biometry and Epidemiology
  6. Univ. Medical Center, Hamburg (Germany). Dept. of Forensic Medicine
  7. Univ. of California, Berkeley, CA (United States). Dept. of Materials Science and Engineering; Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Materials Sciences Division
Publication Date:
Research Org.:
Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
Sponsoring Org.:
USDOE Office of Science (SC), Basic Energy Sciences (BES) (SC-22). Scientific User Facilities Division, Washtington, DC (United States); Alexander von Humboldt Foundation, Bonn (Germany); German Research Foundation (DFG), Bonn (Germany)
OSTI Identifier:
1581747
Grant/Contract Number:  
AC02-05CH11231; BU-2562/3‐1/5‐1
Resource Type:
Accepted Manuscript
Journal Name:
Journal of Bone and Mineral Research
Additional Journal Information:
Journal Volume: 34; Journal Issue: 8; Journal ID: ISSN 0884-0431
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; analysis/quantitation of bone; bone modeling; bone quality; bone remodeling; histomorphometry; osteocytes

Citation Formats

Zimmermann, Elizabeth A., Riedel, Christoph, Schmidt, Felix N., Stockhausen, Kilian E., Chushkin, Yuriy, Schaible, Eric, Gludovatz, Bernd, Vettorazzi, Eik, Zontone, Federico, Püschel, Klaus, Amling, Michael, Ritchie, Robert O., and Busse, Björn. Mechanical Competence and Bone Quality Develop During Skeletal Growth. United States: N. p., 2019. Web. doi:10.1002/jbmr.3730.
Zimmermann, Elizabeth A., Riedel, Christoph, Schmidt, Felix N., Stockhausen, Kilian E., Chushkin, Yuriy, Schaible, Eric, Gludovatz, Bernd, Vettorazzi, Eik, Zontone, Federico, Püschel, Klaus, Amling, Michael, Ritchie, Robert O., & Busse, Björn. Mechanical Competence and Bone Quality Develop During Skeletal Growth. United States. https://doi.org/10.1002/jbmr.3730
Zimmermann, Elizabeth A., Riedel, Christoph, Schmidt, Felix N., Stockhausen, Kilian E., Chushkin, Yuriy, Schaible, Eric, Gludovatz, Bernd, Vettorazzi, Eik, Zontone, Federico, Püschel, Klaus, Amling, Michael, Ritchie, Robert O., and Busse, Björn. Mon . "Mechanical Competence and Bone Quality Develop During Skeletal Growth". United States. https://doi.org/10.1002/jbmr.3730. https://www.osti.gov/servlets/purl/1581747.
@article{osti_1581747,
title = {Mechanical Competence and Bone Quality Develop During Skeletal Growth},
author = {Zimmermann, Elizabeth A. and Riedel, Christoph and Schmidt, Felix N. and Stockhausen, Kilian E. and Chushkin, Yuriy and Schaible, Eric and Gludovatz, Bernd and Vettorazzi, Eik and Zontone, Federico and Püschel, Klaus and Amling, Michael and Ritchie, Robert O. and Busse, Björn},
abstractNote = {Bone fracture risk is influenced by bone quality, which encompasses bone's composition as well as its multiscale organization and architecture. Aging and disease deteriorate bone quality, leading to reduced mechanical properties and higher fracture incidence. Largely unexplored is how bone quality and mechanical competence progress during longitudinal bone growth. In this study, human femoral cortical bone was acquired from fetal (n = 1), infantile (n = 3), and 2- to 14-year-old cases (n = 4) at the mid-diaphysis. Bone quality was assessed in terms of bone structure, osteocyte characteristics, mineralization, and collagen orientation. The mechanical properties were investigated by measuring tensile deformation at multiple length scales via synchrotron X-ray diffraction. We find dramatic differences in mechanical resistance with age. Specifically, cortical bone in 2- to 14-year-old cases exhibits a 160% greater stiffness and 83% higher strength than fetal/infantile cases. The higher mechanical resistance of the 2- to 14-year-old cases is associated with advantageous bone quality, specifically higher bone volume fraction, better micronscale organization (woven versus lamellar), and higher mean mineralization compared with fetal/infantile cases. Our study reveals that bone quality is superior after remodeling/modeling processes convert the primary woven bone structure to lamellar bone. In this cohort of female children, the microstructural differences at the femoral diaphysis were apparent between the 1- to 2-year-old cases. Indeed, the lamellar bone in 2- to 14-year-old cases had a superior structural organization (collagen and osteocyte characteristics) and composition for resisting deformation and fracture than fetal/infantile bone. Mechanistically, the changes in bone quality during longitudinal bone growth lead to higher fracture resistance because collagen fibrils are better aligned to resist tensile forces, while elevated mean mineralization reinforces the collagen scaffold. Thus, our results reveal inherent weaknesses of the fetal/infantile skeleton signifying its inferior bone quality. These results have implications for pediatric fracture risk, as bone produced at ossification centers during children's longitudinal bone growth could display similarly weak points.},
doi = {10.1002/jbmr.3730},
journal = {Journal of Bone and Mineral Research},
number = 8,
volume = 34,
place = {United States},
year = {Mon Jun 17 00:00:00 EDT 2019},
month = {Mon Jun 17 00:00:00 EDT 2019}
}

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Works referenced in this record:

Beginning endochondral ossification in embryonic mouse radii
journal, January 1973


Tibial compression is anabolic in the adult mouse skeleton despite reduced responsiveness with aging
journal, September 2011


The genetics of bone mass and susceptibility to bone diseases
journal, April 2016

  • Karasik, David; Rivadeneira, Fernando; Johnson, Mark L.
  • Nature Reviews Rheumatology, Vol. 12, Issue 6
  • DOI: 10.1038/nrrheum.2016.48

Collagen orientation in compact bone: II. Distribution of lamellae in the whole of the human femoral shaft with reference to its mechanical properties
journal, January 1984

  • Portigliatti Barbos, M.; Bianco, P.; Ascenzi, A.
  • Metabolic Bone Disease and Related Research, Vol. 5, Issue 6
  • DOI: 10.1016/0221-8747(84)90018-3

Muscle force regulates bone shaping for optimal load-bearing capacity during embryogenesis
journal, July 2011


Vitamin D Deficiency Induces Early Signs of Aging in Human Bone, Increasing the Risk of Fracture
journal, July 2013

  • Busse, Björn; Bale, Hrishikesh A.; Zimmermann, Elizabeth A.
  • Science Translational Medicine, Vol. 5, Issue 193
  • DOI: 10.1126/scitranslmed.3006286

Mechanical adaptability of the Bouligand-type structure in natural dermal armour
journal, October 2013

  • Zimmermann, Elizabeth A.; Gludovatz, Bernd; Schaible, Eric
  • Nature Communications, Vol. 4, Issue 1
  • DOI: 10.1038/ncomms3634

Modifications to Nano- and Microstructural Quality and the Effects on Mechanical Integrity in Paget's Disease of Bone: NANO/MICROSTRUCTURE EFFECTS ON MECHANICAL INTEGRITY IN PDB
journal, January 2015

  • Zimmermann, Elizabeth A.; Köhne, Till; Bale, Hrishikesh A.
  • Journal of Bone and Mineral Research, Vol. 30, Issue 2
  • DOI: 10.1002/jbmr.2340

The quantitative study of the orientation of collagen in compact bone slices
journal, January 1990


A SAXS/WAXS/GISAXS Beamline with Multilayer Monochromator
journal, October 2010


Aging and Bone
journal, October 2010


The Development of Metaphyseal Cortex-Implications for Distal Radius Fractures During Growth
journal, August 2001

  • Rauch, Frank; Neu, Christina; Manz, Friedrich
  • Journal of Bone and Mineral Research, Vol. 16, Issue 8
  • DOI: 10.1359/jbmr.2001.16.8.1547

Age-related changes in the plasticity and toughness of human cortical bone at multiple length scales
journal, August 2011

  • Zimmermann, E. A.; Schaible, E.; Bale, H.
  • Proceedings of the National Academy of Sciences, Vol. 108, Issue 35
  • DOI: 10.1073/pnas.1107966108

Spiral twisting of fiber orientation inside bone lamellae
journal, March 2006

  • Wagermaier, W.; S. Gupta, H.; Gourrier, A.
  • Biointerphases, Vol. 1, Issue 1
  • DOI: 10.1116/1.2178386

Human fetal bone development: histomorphometric evaluation of the proximal femoral metaphysis
journal, June 2002


The epidemiology of fractures in England
journal, February 2008

  • Donaldson, L. J.; Reckless, I. P.; Scholes, S.
  • Journal of Epidemiology & Community Health, Vol. 62, Issue 2
  • DOI: 10.1136/jech.2006.056622

Sacrificial bonds and hidden length dissipate energy as mineralized fibrils separate during bone fracture
journal, July 2005

  • Fantner, Georg E.; Hassenkam, Tue; Kindt, Johannes H.
  • Nature Materials, Vol. 4, Issue 8
  • DOI: 10.1038/nmat1428

Bone histomorphometry: a concise review for endocrinologists and clinicians
journal, March 2010

  • Kulak, Carolina A. Moreira; Dempster, David W.
  • Arquivos Brasileiros de Endocrinologia & Metabologia, Vol. 54, Issue 2
  • DOI: 10.1590/S0004-27302010000200002

Aging diminishes lamellar and woven bone formation induced by tibial compression in adult C57BL/6
journal, August 2014


Intracortical remodelling and porosity in the distal radius and post-mortem femurs of women: a cross-sectional study
journal, May 2010


Trends in trabecular architecture and bone mineral density distribution in 152 individuals aged 30–90years
journal, September 2014


Normative data on mineralization density distribution in iliac bone biopsies of children, adolescents and young adults
journal, June 2009


Bone Biology
journal, January 1995


Size-Corrected BMD Decreases During Peak Linear Growth: Implications for Fracture Incidence During Adolescence
journal, December 2006

  • Faulkner, Robert A.; Davison, K. Shawn; Bailey, Donald A.
  • Journal of Bone and Mineral Research, Vol. 21, Issue 12
  • DOI: 10.1359/jbmr.060907

Lehre und Forschung an Verstorbenen: „Mortui vivos docent“
journal, March 2016


Mechanical and structural properties of bone in non-critical and critical healing in rat
journal, September 2014


Dilatational band formation in bone
journal, November 2012

  • Poundarik, A. A.; Diab, T.; Sroga, G. E.
  • Proceedings of the National Academy of Sciences, Vol. 109, Issue 47
  • DOI: 10.1073/pnas.1201513109

The true toughness of human cortical bone measured with realistically short cracks
journal, June 2008

  • Koester, K. J.; Ager, J. W.; Ritchie, R. O.
  • Nature Materials, Vol. 7, Issue 8
  • DOI: 10.1038/nmat2221

How Tough Is Brittle Bone? Investigating Osteogenesis Imperfecta in Mouse Bone: FRACTURE TOUGHNESS OF OIM BONE
journal, May 2014

  • Carriero, Alessandra; Zimmermann, Elizabeth A.; Paluszny, Adriana
  • Journal of Bone and Mineral Research, Vol. 29, Issue 6
  • DOI: 10.1002/jbmr.2172

A study of the relationship between mineral content and mechanical properties of turkey gastrocnemius tendon
journal, June 1995

  • Landis, William J.; Librizzi, Joseph J.; Dunn, Michael G.
  • Journal of Bone and Mineral Research, Vol. 10, Issue 6
  • DOI: 10.1002/jbmr.5650100606

Decreasing incidence of fractures in children: An epidemiological analysis of 1,673 fractures in Malmö, Sweden, 1993–1994
journal, January 1999

  • Tiderius, Carl Johan; Landin, Lennart; Diippe, Henrik
  • Acta Orthopaedica Scandinavica, Vol. 70, Issue 6
  • DOI: 10.3109/17453679908997853

The fracture mechanics of human bone: influence of disease and treatment
journal, September 2015


Bone as a Structural Material
journal, April 2015

  • Zimmermann, Elizabeth A.; Ritchie, Robert O.
  • Advanced Healthcare Materials, Vol. 4, Issue 9
  • DOI: 10.1002/adhm.201500070

Epidemiology of fractures in children and adolescents: Increased incidence over the past decade: a population-based study from northern Sweden
journal, February 2010


Preferred collagen fiber orientation in the human mid-shaft femur
journal, April 2003

  • Goldman, Haviva M.; Bromage, Timothy G.; Thomas, C. David L.
  • The Anatomical Record, Vol. 272A, Issue 1
  • DOI: 10.1002/ar.a.10055

Evidence of structural and material adaptation to specific strain features in cortical bone
journal, September 1996


Mechanistic fracture criteria for the failure of human cortical bone
journal, February 2003

  • Nalla, R. K.; Kinney, J. H.; Ritchie, R. O.
  • Nature Materials, Vol. 2, Issue 3
  • DOI: 10.1038/nmat832

Epidemiology of Childhood Fractures in Britain: A Study Using the General Practice Research Database
journal, September 2004

  • Cooper, Cyrus; Dennison, Elaine M.; Leufkens, Herbert GM
  • Journal of Bone and Mineral Research, Vol. 19, Issue 12
  • DOI: 10.1359/jbmr.040902

Challenges in the Acquisition and Analysis of Bone Microstructure During Growth
journal, November 2016

  • Seeman, Ego; Ghasem-Zadeh, Ali
  • Journal of Bone and Mineral Research, Vol. 31, Issue 12
  • DOI: 10.1002/jbmr.3015

Nanoscale Deformation Mechanisms in Bone
journal, October 2005

  • Gupta, Himadri S.; Wagermaier, Wolfgang; Zickler, Gerald A.
  • Nano Letters, Vol. 5, Issue 10
  • DOI: 10.1021/nl051584b

Bone histomorphometry and bone quality
journal, May 2009

  • Dempster, D. W.; Compston, J. E.; Meunier, P. J.
  • Osteoporosis International, Vol. 20, Issue S3
  • DOI: 10.1007/s00198-008-0702-3

Circularly polarized light standards for investigations of collagen fiber orientation in bone
journal, September 2003

  • Bromage, Timothy G.; Goldman, Haviva M.; McFarlin, Shannon C.
  • The Anatomical Record, Vol. 274B, Issue 1
  • DOI: 10.1002/ar.b.10031

Bone Mineral Density in Girls with Forearm Fractures
journal, January 1998

  • Goulding, A.; Cannan, R.; Williams, S. M.
  • Journal of Bone and Mineral Research, Vol. 13, Issue 1
  • DOI: 10.1359/jbmr.1998.13.1.143

The effects of ageing and changes in mineral content in degrading the toughness of human femora
journal, February 1996


Three-dimensional coherent diffractive imaging on non-periodic specimens at the ESRF beamline ID10
journal, March 2014


Standardized nomenclature, symbols, and units for bone histomorphometry: A 2012 update of the report of the ASBMR Histomorphometry Nomenclature Committee
journal, December 2012

  • Dempster, David W.; Compston, Juliet E.; Drezner, Marc K.
  • Journal of Bone and Mineral Research, Vol. 28, Issue 1
  • DOI: 10.1002/jbmr.1805

The mechanical properties of bone tissue in children
journal, January 1975


Epidemiology of fractures of the distal end of the radius in children as associated with growth.
journal, January 1989


Influence of mineral content and composition on graylevels in backscattered electron images of bone
journal, January 1993

  • Skedros, John G.; Bloebaum, Roy D.; Bachus, Kent N.
  • Journal of Biomedical Materials Research, Vol. 27, Issue 1
  • DOI: 10.1002/jbm.820270108

Mineral maturity and crystallinity index are distinct characteristics of bone mineral
journal, January 2010

  • Farlay, Delphine; Panczer, Gérard; Rey, Christian
  • Journal of Bone and Mineral Metabolism, Vol. 28, Issue 4
  • DOI: 10.1007/s00774-009-0146-7

FT-IR imaging of native and tissue-engineered bone and cartilage
journal, May 2007


Long bone maturation is driven by pore closing: A quantitative tomography investigation of structural formation in young C57BL/6 mice
journal, August 2015


Periosteal Bone Formation — A Neglected Determinant of Bone Strength
journal, July 2003


Developing bones are differentially affected by compromised skeletal muscle formation
journal, May 2010


Bone Biology
journal, January 1995


The effects of ageing and changes in mineral content in degrading the toughness of human femora
journal, September 1997


Erratum: The genetics of bone mass and susceptibility to bone diseases
journal, July 2016

  • Karasik, David; Rivadeneira, Fernando; Johnson, Mark L.
  • Nature Reviews Rheumatology, Vol. 12, Issue 8
  • DOI: 10.1038/nrrheum.2016.118

Nanoscale deformation mechanisms in bone
journal, May 2009


Works referencing / citing this record:

Platelet‐rich fibrin and collagen membrane in the preservation of the alveolar bone: Feasibility of the elemental inorganic composition and scanning electron microscopy analysis
journal, August 2019

  • Dias, Fernando José; Arias, Alain; Borie, Eduardo
  • Microscopy Research and Technique, Vol. 82, Issue 12
  • DOI: 10.1002/jemt.23368

Sexually Dimorphic Influence of Neonatal Antibiotics on Bone
journal, June 2019

  • Pusceddu, Matteo M.; Stokes, Patricia J.; Wong, Alice
  • Journal of Orthopaedic Research, Vol. 37, Issue 10
  • DOI: 10.1002/jor.24396

Compositional and mechanical properties of growing cortical bone tissue: a study of the human fibula
journal, November 2019


Multiscale bone quality analysis in osteoarthritic knee joints reveal a role of the mechanosensory osteocyte network in osteophytes
journal, January 2020


Compositional and mechanical properties of growing cortical bone tissue: a study of the human fibula
text, January 2019