Osteoporosis (OP) results in a reduction in the mechanical competence of the bone tissue of the sufferers. In skeletal sites such as the proximal femur and the vertebrae, OP manifests itself in low trauma fragility fractures which are debilitating for the patient. The relationships between the compressive strength of cancellous tissue and its apparent density are well established in studies of the past. Recently the authors have presented a method able to assess the fracture toughness properties of cancellous bone (1), a challenging cellular material which can exhibit large elasto-plastic deformations. The in-vitro measurement of fracture toughness alongside the customary compressive strength can provide a comprehensive assessment of the mechanical capacity of cancellous bone, which will reflect closer its ability to resist crack initiation. The aims of the present study were: (1) to examine whether the observed fracture toughness deterioration can also be detected by non-invasive quantitative ultrasound (QUS); and (2) to provide rational evidence for the well proven ability of QUS to predict directly ‘risk of fracture’. 20 femoral heads were obtained from donors undergoing emergency surgery for a fractured neck of femur. QUS investigations of the calcaneus, proximal phalanx and distal radius were undertaken within 72 hours of surgery. 128 fracture toughness samples and 20 compression cores were manufactured and tested. Two clinical QUS systems were used to obtain in-vivo scan data and then directly compared those to the density, porosity and the fracture mechanics of tissue extracted from the same individuals. The results demonstrated not only that there was a significant link between in-vivo determined QUS values for the calcaneus and finger to the density of the density of the femoral head; but that there was also a significant link between the QUS results from the calcaneus and the fracture toughness of the cancellous bone from the femoral head. These results point towards a systemic effect of osteoporosis which affects similarly different parts of the skeleton and supports the use of clinical QUS systems as a diagnostic tool for the prediction of fracture risk.