Geometric and material contributions to whole bone structural behavior in GDF-7-deficient mice.

The growth/differentiation factors (GDFs) are a subfamily of bone morphogenetic proteins (BMPs) known to play a role in a variety of skeletal processes. Previous work using the brachypod mouse demonstrated that mice deficient in GDF-5 have long bones with diminished material properties and ash content compared with control littermates. Our aim was to examine the role of a related GDF family member, GDF-7 (BMP-12), in cortical bone by examining the geometric and material contributions to whole bone structural behavior in GDF-7-deficient mice. Femora from 16-week-old GDF-7 -/- animals had significantly smaller bone cross-sectional geometric parameters (e.g., -20% medial/lateral and anterior/posterior moments of inertia). Despite having smaller bone cross-sections, all structural parameters obtained from four-point bending tests were comparable to those of wild-type bones due to elevated cortical bone material properties (+18% modulus of elasticity, +28% yield strength, and +18% ultimate strength). No significant differences in ash content or collagen content were detected, however. These data suggest that GDF-7 deficiency is associated with elevated cortical bone material properties that compensate for decreased geometric properties, thereby preserving bone structural integrity. The compositional and/or microstructural bases for these altered material properties remain to be determined, however.