Tissue material properties, whole-bone morphology and mechanical behavior in the mouse model of Marfan syndrome.

Marfan syndrome (MFS) is a connective tissue disorder caused by pathogenic mutations in FBN1. In bone, the protein fibrillin-1 is found in the extracellular matrix where it provides structural support of elastic fiber formation, stability for basement membrane, and regulates the bioavailability of growth factors. Individuals with MFS exhibit a range of skeletal complications including low bone mineral density and long bone overgrowth. However, it remains unknown if the bone phenotype is caused by alteration of fibrillin-1's structural function or distortion of its interactions with bone cells. To assess the structural effects of the fibrillin-1 mutation, we characterized bone curvature, microarchitecture, composition, porosity, and mechanical behavior in the mouse model of MFS. Tibiae of 10, 26, and 52-week-old female and littermate control (LC) mice were analyzed. Mechanical behavior was assessed via in vivo strain gauging, finite element analysis, three-point bending, and nanoindentation. Tibial bone morphology and curvature were assessed with micro computed tomography (μCT). Bone composition was measured with Fourier transform infrared (FTIR) imaging. Vascular and osteocyte lacunar porosity were assessed by synchrotron computed tomography. mice exhibited long bone overgrowth and osteopenia consistent with the MFS phenotype. Trabecular thickness was lower in mice but cortical bone microarchitecture was similar in and LC mice. Whole bone curvature was straighter below the tibio-fibular junction in the medial-lateral direction and more curved above in LC compared to mice. The bone matrix crystallinity was 4 % lower in mice compared to LC, implying that mineral platelets in LCs have greater crystal size and perfection than mice. Structural and mechanical properties were similar between genotypes. Cortical diaphyseal lacunar porosity was lower in mice compared to LC; this was a result of the average volume of an individual osteocyte lacunae being smaller. These data provide valuable insights into the bone phenotype and its contribution to fracture risk in this commonly used mouse model of MFS.