4.6 Article

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

Journal

JOURNAL OF BONE AND MINERAL RESEARCH
Volume 16, Issue 10, Pages 1854-1862

Publisher

AMER SOC BONE & MINERAL RES
DOI: 10.1359/jbmr.2001.16.10.1854

Keywords

genetics; bone biomechanics; skeletal fragility; inbred mice; bone density; bone quality

Funding

  1. NCRR NIH HHS [RR12305] Funding Source: Medline
  2. NIAMS NIH HHS [AR44927] Funding Source: Medline

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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.

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