482, p < 0.01) while the wild type group exhibited no correlation (Pearson's r = − 0.007, p > 0.05). Much research at the macro-scale has assumed that an increase in bone mineral density is associated with increased bone stiffness. Indeed, the gold standard for measuring therapeutic benefits of pharmaceutical therapies is measuring bone mass typically with DEXA or

pQCT. Here we show in the extreme example of the oim model that macro-scale properties do not accurately reflect the mechanics at smaller length scales and that increases in bone matrix mineralization are not always associated with increased bone elastic properties. Osteogenesis imperfecta provides an interesting model to explore the mineral/protein Saracatinib in vitro relationship in the bone matrix composite, as defects in the collagen influence the structure and mechanics at multiple length scales. At the macroscopic scale, oim bone was weak (decrease of Fult

and σult) and brittle (little post-yield deformation) as expected. The calculated elastic moduli of oim and wild type bone were not significantly different and displayed a very high variability (16.8% and 10.8% respectively). This finding, in combination with the discrepancy observed in the previous 3 point bending tests [14], [15] and [16], illustrates that the assumptions required in the beam theory (pure bending, constant bone cross-section and homogeneous, isotropic bone material properties) actually over-simplify the bone properties and may not accurately capture the intrinsic bone matrix Alpelisib clinical trial elasticity as noted by previous studies [36]. In addition, the whole bone Resveratrol estimates of modulus include the effects of porosity, which is significantly

increased in oim, thereby providing an overall modulus that includes the matrix and the voids. This justifies an investigation of bone properties at a smaller scale with more dedicated techniques for determining matrix mechanical properties. When measuring the bone properties at the micron length scales, it is not feasible to maintain large sample sizes particularly when the variation of properties within a sample has equal (or even greater) variance than between samples. To preclude biasing our measures at higher length scale, we chose the tested samples randomly from the wild type and oim groups and assessed how local variations in mineralization affected local elastic properties within a bone. At the microscopic (matrix) scale, nanoindentation revealed a decrease of elasticity and a slight increase of the resistance to plastic deformation (i.e. less plastic deformation) in the oim bone matrix compared to wild type mice. Our local nanoindentation results are comparable to the findings of Mehta et al. who also measured a decrease in elastic modulus in oim using ultrasound critical-angle reflectometry [19]. It should be noted that it was necessary to dehydrate and fully infiltrate our samples with PMMA for qBSEM analysis.