Understanding of the genetic and environmental factors contributing to the differences in fracture rates between young and old, between women and men, and between races is limited. The reasons for this may partly relate to the lack of a detailed understanding of the structural basis of bone fragility. This information, although difficult to obtain because of the invasiveness of bone biopsy, will be required if advances are to occur. aBMD cannot be relied upon as an endpoint in the study of the pathophysiology of osteoporosis. Advances will require the description of the age-, gender and race-specific means and variances in trabecular number, thickness, spacing and orientation, cortical thickness, and bone size and shape in women and men of different racial groups. Subsequent comparison of the structures in young versus old, female versus male, and in racial groups may reveal the structural differences from which inferences may be made concerning the differences in fracture rates between these groups. By defining the structural basis for bone fragility, the genetic and modifiable environmental determinants of these structures may then be identified, providing hypotheses to be tested in randomized trials aimed at reducing the incidence of fractures in these groups.