Effect of abnormal mineralization on the mechanical behavior of x-linked hypophosphatemic mice femora

The Hyp mouse is an established animal model of X-linked hypophosphatemia, one of the most common genetic forms of metabolic bone disease in humans. This study describes the first determination of whole bone mechanical behavior in the heterozygous male and female Hyp mouse. Femora from 12-week-old mice were tested in torsion. The contribution of structural and material properties to mechanical behavior was determined by geometrical evaluation prior to testing and by analysis of the diaphyseal mineral after testing. The male and female Hyp femora were found to undergo significantly more angular deformation at failure than the same sex normal femora (36.02 ± 10.64 vs. 9.88 ± 3.50 rad/m for the females and 56.29 ± 16.18 vs. 9.95 ± 3.16 rad/m for the males) and to have a significantly lower structural stiffness (0.854 ± 0.297 x 10 -3 vs. 3.04 ± 0.87 x 10 -3 [N-m/(rad/m)] for the females and 0.382 ± 0.239 x 10 -3 vs. 3.66 ± 1.15 x 10 -3 [N-m/(rad/m)] for the males). The male Hyp femora had a significantly lower failure torque than male normal femora (1.58 ± 0.62 x 10 -2 vs. 3.44 ± 1.57 x 10 -2 N-m). Because the polar movement of inertia, a geometrical property that affects torsional behavior, was not significantly different between the Hyp femora and the same sex normals, differences in mechanical behavior were attributed to material properties. Ground Hyp diaphyseal bone had a significantly lower mineral (ash) content (59.94 ± 2.07% vs. 68.88 ± 0.68% for the females and 56.09 ± 0.17% vs. 68.41 ± 0.65% for the males) and a higher calcium-to-phosphorus molar ratio (1.672 ± 0.008 vs. 1.621 ± 0.012 for the females and 1.692 ± 0.002 vs. 1.625 ± 0.022 for the males) than the same sex normal bones. A reduction in carbonate content of the mineral in the Hyp femora was also noted. These results are indicative of increased bone turnover. In addition, the mineral content of the Hyp female femora was significantly greater than that of the Hyp male femora. Analysis by Fourier transform infrared microscopy in conjunction with light microscopy and scanning electron microscopy revealed hypomineralized periosteocytic and perivascular lesions in the Hyp femora that penetrated through the endosteal and periosteal surfaces. It was concluded that the altered mechanical properties of the Hyp femora are attributed to the reduced quantity and quality of mineral.