Quasi-brittle fracture mechanics to assess ex vivo Raloxifene treatment of human cortical bone

Osteoporosis patients are growing in number, but treatments do not fully reduce fracture risk. Fracture mechanics, historically applied to engineering materials, provides tools to understand the non-linear behavior in cortical bone fractures and inform further treatment opportunities. Specifically, this study demonstrates the relevance of quasi-brittle fracture in the assessment of human cortical bone. Human cortical bone from one male donor femur was sectioned into notched prismatic bars and randomly assigned to two treatment groups: a control group and a treatment group. Treatment consisted of ex vivo soaking with Raloxifene, an FDA-approved pharmaceutical. In-situ four-point bend fracture experiments were conducted in the beamline of a 3D X-ray microscope under physiologic conditions. Fracture process zone (FPZ) length was measured directly from images. Quasi-brittle fracture mechanics (QBFM) theory was applied to assess treatment effects and determine bone tissue properties. QBFM scaling laws are applied to theoretically predict treatment effects at the organ length scale. In both treatment groups, the FPZ is large compared to the microstructure and sample dimension. Raloxifene treatment increases the tissue FPZ length and tissue fracture toughness of the material. Raloxifene treatment significantly decreases the brittleness of bone tissue at the experimental and organ length scales; non-linear relationships emerge from both microstructural influences on the fracture process. Due to the large FPZ and quasi-brittle behavior of the tissue, size effects on apparent fracture toughness emerge. The QBFM theory allows for understanding individual experiments in the context of size and treatment.