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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 cohortmore » 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.« 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. 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., and Busse, Björn. Mon . "Mechanical Competence and Bone Quality Develop During Skeletal Growth". United States. doi:10.1002/jbmr.3730.
@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 = {2019},
month = {6}
}

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