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How Tough Is Brittle Bone? Investigating Osteogenesis Imperfecta in Mouse Bone
Open accessAbstract
The multiscale hierarchical structure of bone is naturally optimized to resist fractures. In osteogenesis imperfecta, or brittle bone disease, genetic mutations affect the quality and/or quantity of collagen, dramatically increasing bone fracture risk. Here we reveal how the collagen defect results in bone fragility in a mouse model of osteogenesis imperfecta (oim), which has homotrimeric α1(I) collagen. At the molecular level, we attribute the loss in toughness to a decrease in the stabilizing enzymatic cross-links and an increase in nonenzymatic cross-links, which may break prematurely, inhibiting plasticity. At the tissue level, high vascular canal density reduces the stable crack growth, and extensive woven bone limits the crack-deflection toughening during crack growth. This demonstrates how modifications at the bone molecular level have ramifications at larger length scales affecting the overall mechanical integrity of the bone; thus, treatment strategies have to address multiscale properties in order to regain bone toughness. In this regard, findings from the heterozygous oim bone, where defective as well as normal collagen are present, suggest that increasing the quantity of healthy collagen in these bones helps to recover toughness at the multiple length scales. © 2014 American Society for Bone and Mineral Research.
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Studies of osteogenesis imperfecta indicate that fewer enzymatic cross-links, more nonenzymatic cross-links, increased porosity, and reduced fraction of lamellar bone may all work to increase tissue brittleness.
“For example, studies of osteogenesis imperfecta, a group of rare genetic disorders that affect type I collagen and are characterized by low bone toughness, indicate that fewer enzymatic cross-links, more nonenzymatic cross-links, increased porosity, and reduced fraction of lamellar bone may all work to increase tissue brittleness (76).”
From Bone Mechanical Properties in Healthy and Diseased States (2018) · cites this paper as [76]
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Bone Mechanical Properties in Healthy and Diseased States
Morgan, E. F., Unnikrisnan, G. U., & Hussein, A. I. (2018) · Annual Review of Biomedical Engineering · doi:10.1146/annurev-bioeng-062117-121139 · Cited by 1,026
“For example, studies of osteogenesis imperfecta, a group of rare genetic disorders that affect type I collagen and are characterized by low bone toughness, indicate that fewer enzymatic cross-links, more nonenzymatic cross-links, increased porosity, and reduced fraction of lamellar bone may all work to increase tissue…”
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Metadata
- Authors
- Carriero, A., Zimmermann, E. A., Paluszny, A., Tang, S. Y., Bale, H., Busse, B., Alliston, T., Kazakia, G., Ritchie, R. O., & Shefelbine, S. J.
- Affiliations
- Lawrence Berkeley National Laboratory (US)
- Imperial College London (GB)
- University of California, San Francisco (US)
- Department of Materials Science and EngineeringUniversity of California BerkeleyBerkeleyCAUSA
- Corresponding author
- Carriero, Alessandra
- ORCID
- Venue
- Journal of Bone and Mineral Research
- Publisher
- Oxford University Press (OUP)
- Published
- 2014-01-13
- Volume
- 29
- Issue
- 6
- Pages
- 1392-1401
- ISSN
- 0884-0431 (ISSN-L)
- 1523-4681
- PMC
- PMC4477967
- OpenAlex
- W1938154233
- Cited by
- 149
- References
- 62
- Citations by year
- 2026: 9 · 2025: 10 · 2024: 8 · 2023: 8 · 2022: 7 · 2021: 16 · 2020: 30 · 2019: 10 · 2018: 7 · 2017: 7 · 2016: 15 · 2015: 11 · 2014: 11
- FWCI
- 9.61
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
- Locations
- Journal of Bone and Mineral Research (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Spiral (Imperial College London) (submittedVersion)
- Funders
- U.S. Department of Energy (-AC02-05CH11231, 05CH11231, DE AC02 05CH11231, DE-AC02-)
- Royal Academy of Engineering
- Office of Science (DEAC02–05CH11231, AC02-05CH11231, DE-AC02)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (K01AR056734, P30AR066262, F32AR053446)
- National Institute of Dental and Craniofacial Research (R01DE019284)
- Lawrence Berkeley National Laboratory (AC02‐05CH11231, DE-AC02-05CH11231, 05CH11231)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Connective tissue disorders research
- Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Dermatological and Skeletal Disorders
- Keywords
- osteogenesis imperfecta, bone toughness, collagen, alpha1(I) collagen, crack propagation, crack deflection toughening, woven bone, bone plasticity
- MeSH terms
- Animals, Biomechanical Phenomena, Bone and Bones, Computer Simulation, Mice, Inbred C57BL, Osteogenesis Imperfecta, Tomography, X-Ray Computed, X-Ray Diffraction, Bone Density, Glycation End Products, Advanced, Spectroscopy, Fourier Transform Infrared, Fibrillar Collagens, Fractures, Bone, Mice, Scattering, Small Angle
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