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 hypophosphate mia, one of the most common genetic forms of metabolic bone disease in humans. This study describes the first determination of whole bone me chanical behavior in the heterozygous male and female Hyp mouse. Femor a from 12-week-old mice were tested in torsion. The contribution of st ructural and material properties to mechanical behavior was determined by geometrical evaluation prior to testing and by analysis of the dia physeal mineral after testing. The male and female Hyp femora were fou nd to undergo significantly more angular deformation at failure than t he 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 prop property that affects torsional behavior, was not significantly different between the Hyp femora and the same sex normal, differences in mechanical behavior were attributed to material properties. Ground Hyp diaphyseal bone had a significantly lower mineral (ash) content (5 9.94 +/- 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 n ormal bones. A reduction in carbonate content of the mineral in the Hy p femora was also noted. These results are indicative of increased bon e turnover. In addition, the mineral content of the Hyp female femora was significantly greater than that of the Hyp male femora. Analysis b y Fourier transform infrared microscopy in conjunction with light micr oscopy and scanning electron microscopy revealed hypomineralized perio steocytic and perivascular lesions in the Hyp femora that penetrated t hrough the endosteal and periosteal surfaces. It was concluded that th e altered mechanical properties of the Hyp femora are attributed to th e reduced quantity and quality of mineral.