Evolving role of imaging in the evaluation of bone structure.

A top priority in osteoporosis research is the identification of the structural parameters that contribute to variations in the strength of bone and the risk of fragility fractures. For the past two decades, DXA has been used to diagnose osteoporosis based on measurements of BMC and areal BMD. Whereas DXA has become the most commonly used technique worldwide to predict fracture risk and assess response to therapy, it is based on a 2D interpretation of the 3D skeleton and provides limited information on the structural properties of bone. Other imaging modalities such as CT and MR offer considerably greater characterization of bone architecture, but their cost and inaccessibility have precluded them from becoming widely adopted clinically. Recent advances, however, have led to the introduction of more manageable CT and MR techniques that provide 3D assessments of the appendicular skeleton. In this issue of the Journal, two studies by Wang et al. and Walker et al. highlight how progress in analyzing variations in bone structure among humans comes from the use of these techniques in comparative studies to identify the skeletal differences between persons who are susceptible to fractures and those who are not. Using high-resolution peripheral QCT (HR-pQCT), Wang et al. and Walker et al. examined the differences in macroand microarchitecture of the peripheral skeleton between young white and Chinese women. Available data indicate that Asian women have a lower incidence of hip and forearm fractures despite consistently being reported to have lower areal BMD values as measured by DXA compared with white women and other racial groups. With the detailed analysis of cancellous and cortical bone in the distal radius and tibia that HR-pQCT provides, these two studies arrived at strikingly similar explanations for this paradox. Both Wang et al. and Walker et al. found Asian women to have significantly greater cortical thickness and density, as well as greater trabecular thickness at both sites. Trabecular number was also greater in the distal tibia but not in the radius in both studies. The authors reasonably suggest that these anatomical differences are likely contributors to the lower risk for fractures in the appendicular skeleton of Chinese women. In contrast, the study by Walker et al. found the areal BMD by DXA of the axial and appendicular skeleton did not differ between races. It is remarkable that such comparable results were obtained in both studies with relatively small cohorts of white and Chinese women from two different continents with different environmental conditions. This consistency underscores the power of 3D techniques and the generalizability of the results. It is also likely a reflection of the young age of the participants in both studies, because the magnitude of the genetic effect on bone mass and bone architecture is higher in young premenopausal women. As indicated by these two studies, advances in our understanding of the great variations in bone structure in the appendicular skeleton among humans will likely come from improved 3D imaging technology, much like prior studies using CT had done for our knowledge of the axial skeleton. Conventional CT advanced our understanding of the relationships between vertebral size and fracture risk beyond the knowledge that could be provided by using DXA. The use of CT indicated that men have larger vertebrae than women, even after adjusting for differences in body size, and that the lower vertebral mass of women compared with men resulted from early sex differences in the size of bone rather than differences in bone densities. 3D techniques also helped establish vertebral size as an important determinant of vertebral fracture risk. Additionally, the ability of 3D techniques to assess BMD without soft tissue errors was key to establishing that peak BMD in the axial skeleton, a major contributor to osteoporosis in the elderly, is achieved soon after sexual maturity and not in the third, fourth, or fifth decades as indicated by DXA. CT and pQCT have the advantages of allowing for the segmentation of trabecular and cortical bone, as well as for measurements of bone geometry, cortical density, and the apparent density of trabecular bone. Further advances, as reported by Wang et al. and Walker et al., came from the introduction of HR-pQCT equipment with the ability to