Moreover, as the same specimen preparation and indentation protocols were used on both wild type and oim specimens, the impact on bone matrix properties should be equivalent on both groups and should not affect the relative difference between the two. The differences between whole bone elastic

modulus values (~ 7 GPa) and matrix level elastic modulus values (~ 30–35 GPa) are in line with the findings of other studies [36] and result primarily from beam theory simplifications at the whole bone level, porosity (included at the whole bone scale but not at the microscopic scale), and the sample preparation used for the nanoindentation protocol. Quantitative backscattered analysis revealed a higher bone Bioactive Compound Library solubility dmso matrix mineralization in the oim bones compared to their wild

type counterpart (as illustrated by more red/pink pixels in oim mice in Fig. 1). In both wild type and oim groups, females displayed higher mineralization with no increase in elastic modulus compared to their male counterpart. Similarly, compared to wild type mice, the bone matrix of oim mice was more mineralized but displayed a lower average elastic modulus. This implies that the “extra” mineral is not mechanically contributing to matrix elastic properties. While such observations on oim matrix mineralization are in agreement with the literature [17], [19], [21] and [26], this is the first time that the bone matrix elasticity, plasticity and mineralization were examined together at the

microscopic Small molecule library scale. These results can help to explain how matrix properties result in bone brittleness at the macroscopic scale. For a same amount of energy deployed during a load, while the wild type bone matrix remains in the elastic domain, the oim bone matrix will reach the plastic domain where its higher resistance to plastic deformation does not allow further plastic deformation, triggering the catastrophic fracture of the bone and explaining the increased bone brittleness. To investigate the structural features causing the bone matrix decrease in elastic modulus despite high mineralization, we examined the crystal structure using transmission PJ34 HCl electron microscopy (TEM). To our knowledge, this is the first time that TEM has been used to assess crystal size, structure, and organization in oim bone. Our TEM images revealed that the apatite crystals in the oim bone matrix were significantly smaller, more tightly packed and not as well aligned as the wild type which is in agreement with previous small-angle X-ray scattering observations [25] and [26]. The extremely tight packing of the small apatite crystals may explain the high mineralization of the oim bone matrix. The disorganization of crystals in oim mice may be partially explained by the difference of bone tissue fabrics.