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

The contribution of genetic and environmental factors to variations in bone quality are understood poorly. We tested whether bone brittleness varies w ith genetic background using the A/J and C57BL/6J inbred Mouse strains. Who le bone four-point bending tests revealed a 70% decrease in postyield defle ction of A/J femurs compared with C57BL/6J, indicating that A/J femurs fail ed in a significantly more brittle manner. Cyclic loading studies indicated that A/J femurs accumulated damage differently than C57BL/6J femurs, consi stent with their increased brittleness. Differences in matrix composition a lso were observed between the two mouse strains. A/J femurs had a 4.5% incr ease in ash content and an 11.8% decrease in collagen content. Interestingl y, a reciprocal relationship was observed between femoral geometry and mate rial stiffness; this relationship may have contributed to the brittle pheno type of A/J femurs. A/J femurs are more slender than those of C57BL/6J femu rs; however, their 47% smaller moment of inertia appeared to be compensated by an increased tissue stiffness at the expense of altered tissue damageab ility. Importantly, these differences in whole bone mechanical properties b etween 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 d etermined differences in whole bone architecture, bone matrix composition, and mechanisms of cyclical damage accumulation.