Comparison of bone tissue properties in mouse models with collagenous and non-collagenous genetic mutations using...

Understanding how the material properties of bone tissue from the various forms of osteogenesis imperfecta (OI) differ will allow us to tailor treatment regimens for affected patients. To this end, we characterized the bone structure and material properties of two mouse models of OI, the osteogenesis imperfecta mouse (oim/oim) and fragilitas ossium (fro/fro), in which bone fragility is due to a genetic defect in collagen type I and a defect in osteoblast matrix mineralization, respectively. Bones from 3 to 6 month old animals were examined using Fourier transform infrared spectroscopic imaging (FTIRI), microcomputed tomography (micro-CT), histology, and biochemical analysis. The attributes of oim/oim bone tissue were relatively constant over time when compared to wild type animals. The mineral density in oim/oim cortices and trabecular bone was higher than wild type while the bones had thinner cortices and fewer trabeculae that were thinner and more widely spaced. The fro/fro animals exhibited osteopenic attributes at 3 months. However, by 6 months, their spectroscopic and geometric properties were similar to wild type animals. Despite the lack of a specific collagen defect in fro/fro mice, both fro/fro and oim/oim genotypes exhibited abnormal collagen crosslinking as determined by FTIRI at both time points. These results demonstrate that abnormal extracellular matrix assembly plays a role in the bone fragility in both of these models.