The effect of growth/differentiation factor-5 deficiency on femoral composition and mechanical behavior in mice

A subclass of the bone morphogenetic proteins (BMPs), known as growth/differentiation factors (GDFs) 5, 6, and 7, have been shown to affect several skeletal processes, including endochondral ossification, synovial joint formation, and tendon and ligament repair. Mice deficient in GDF-5 have also been shown to exhibit biomechanical abnormalities in tendon that may be associated with altered type I collagen. The purpose of this study was to investigate the effect of GDF-5 deficiency on another type I collagen-rich tissue: cortical bone. Analyses were performed on femora from 8-week-old GDF-5-deficient male brachypodism mice. We hypothesized that GDF-5-deficient bones would exhibit altered geometric, structural, and material properties compared with control littermates. Mutant animals were significantly smaller in body mass than controls (−21%). Geometrically, mutant long bones were significantly shorter (−25%), had a lower polar moment of inertia (−34%), and a lower geometric strength indicator (analogous to the section modulus of a circular section) (−30%). When normalized by body mass, however, geometric differences were no longer significant. Structurally, GDF-5-deficient femora were weaker (−31%) and more compliant (−57%) than controls when tested to failure in torsion. Lower bone structural stiffness in the mutants was not completely explained by the smaller bone geometry, because mutant bones exhibited a significantly lower effective shear modulus (−36%). Although body mass did not fully explain the reduced structural strength in mutant bones, strength differences were adequately explained by bone cross-sectional geometry; maximum effective shear stress was not significantly different between mutants and controls, despite a statistically significant 6% lower ash fraction in mutant femora. No significant difference was detected in collagen content, as indicated by hydroxyproline per dry mass.