How tough is brittle bone? Investigating osteogenesis imperfecta in mouse bone

Alessandra Carriero, Elizabeth A. Zimmermann, Adriana Paluszny, Simon Y. Tang, Hrishikesh Bale, Bjorn Busse, Tamara Alliston, Galateia Kazakia, Robert O. Ritchie, Sandra J. Shefelbine

Research output: Contribution to journalArticlepeer-review

66 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)1392-1401
Number of pages10
JournalJournal of Bone and Mineral Research
Volume29
Issue number6
DOIs
StatePublished - Jun 2014

Keywords

  • BONE FRACTURE
  • BRITTLE BONE
  • CRACK GROWTH
  • CRACK INITIATION
  • FRACTURE MECHANICS
  • MOUSE BONE

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