title: Bone brittleness varies with genetic background in A/J and C57BL/6J inbred mice.
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.
authors.affiliation: Department of Orthopedics, Mount Sinai School of Medicine, New York, New York 10029, USA.
authors.forename: K J
authors.initials: KJ
authors.lastname: Jepsen
authors.forename: D E
authors.initials: DE
authors.lastname: Pennington
authors.forename: Y L
authors.initials: YL
authors.lastname: Lee
authors.forename: M
authors.initials: M
authors.lastname: Warman
authors.forename: J
authors.initials: J
authors.lastname: Nadeau
mesh_terms: D000818:Animals; D005269:Femur / Q000502:physiology*; D008297:Male; D051379:Mice; D008805:Mice, Inbred A; D008810:Mice, Inbred C57BL; D013045:Species Specificity; D013314:Stress, Mechanical