Bone brittleness varies with genetic background in A/J and C57BL/6J inbred mice

K. J. Jepsen, D. E. Pennington, Y. L. Lee, M. Warman, J. Nadeau

Research output: Contribution to journalArticlepeer-review

96 Scopus citations

Abstract

The contribution of genetic and environmental factors to variations in bone quality are understood poorly. We tested whether bone brittleness varies with genetic background using the A/J and C57BL/6J inbred mouse strains. Whole bone four-point bending tests revealed a 70% decrease in postyield deflection of A/J femurs compared with C57BL/6J, indicating that A/J femurs failed in a significantly more brittle manner. Cyclic loading studies indicated that A/J femurs accumulated damage differently than C57BL/6J femurs, consistent with their increased brittleness. Differences in matrix composition also were observed between the two mouse strains. A/J femurs had a 4.5% increase in ash content and an 11.8% decrease in collagen content. Interestingly, a reciprocal relationship was observed between femoral geometry and material stiffness; this relationship may have contributed to the brittle phenotype of A/J femurs. A/J femurs are more slender than those of C57BL/6J femurs; however, their 47% smaller moment of inertia appeared to be compensated by an increased tissue stiffness at the expense of altered tissue damageability. Importantly, these differences in whole bone mechanical properties between A/J and C57BL/6J femurs could not have been predicted from bone mass or density measures alone. The results indicated that bone brittleness is a genetically influenced trait and that it is associated with genetically determined differences in whole bone architecture, bone matrix composition, and mechanisms of cyclical damage accumulation.

Original languageEnglish
Pages (from-to)1854-1862
Number of pages9
JournalJournal of Bone and Mineral Research
Volume16
Issue number10
DOIs
StatePublished - 2001

Keywords

  • Bone biomechanics
  • Bone density
  • Bone quality
  • Genetics
  • Inbred mice
  • Skeletal fragility

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