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For the clinician, predicting the fracture risk for individual patients is mainly restricted to the quantitative analysis of bone density. Several studies have shown that bone strength, an indicator for bone fracture risk, is only predicted moderately by bone density, indicating that there are other factors influencing bone competence. However, the relative importance of “bone quantity” and “bone quality” remains poorly understood. The objectives of this article are to describe some of the techniques used to measure the microarchitectural aspects of bone quality, how they can be quantified, and how these quantitative endpoints can be used in the assessment of bone competence. Special focus will be on the distal radius, a site with a high fracture incidence. With the introduction of high-resolution in vivo bone imaging systems, a new generation of imaging instruments has entered the arena allowing the reconstruction of the 3-dimensional microarchitecture of the bones at the wrist, thereby giving researchers and clinicians a powerful tool for the quantitative assessment of bone microstructure. In combination with large-scale finite element modeling, these methodologies have reached a level that it is now becoming possible to assess bone stiffness and strength in humans in a clinical setting. The procedure can help improve predictions of fracture risk, clarify the pathophysiology of skeletal diseases, and monitor the response to therapy.