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Early detection of fracture risk is important for initiating treatment and improving outcomes from both physiologic and pathologic causes of bone loss. While bone mineral density (a quantity measure) has traditionally been used for this purpose, alternative structural imaging parameters (quality measures) are proposed to better predict bone's true mechanical properties. To further elucidate this, trabecular bone from cadaveric human calcanei were used to evaluate the interrelationship of mechanical and structural parameters using mechanical testing, dual energy X-ray absorptiometry (DXA) scanning, and micro computed tomography (microCT) imaging. Directional specific structural properties were assessed in three-dimensional (3-D) and correlated to mechanical testing and DXA. The results demonstrated that microCT-derived indices of bone quality (i.e., volume fraction and structural model index) are better than DXA-derived bone mineral density for the prediction of the mechanical parameters of bone (i.e., elastic modulus, yield stress, and ultimate stress). Diagnostically, this implies that future work on the early prediction of fracture risk should focus as much on bone quality as on quantity. Furthermore, the results of this study show that a loss of bone primarily affects the connectedness and overall number of trabeculae. Ultimate stress, however, is better correlated with trabecular number than thickness. As such, primary prevention of osteoporosis may be more important than later countermeasures for bone loss.