Quantifying the material and structural determinants of bone strength

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744 M.L. Bouxsein, E. Seeman / Best Practice & Research Clinical Rheumatology 23 (2009) 741–753 Fig. 1. Quantitative computed tomography image of the lumbar spine, showing bone density phantom, and distinct analysis of cortical and trabecluar bone compartments. Images courtesy of Dr. Thomas Lang, UCSF. midlife [49]. Effects of drug therapy on cancellous and cortical bone have been documented using QCT [53–58]. There are many cross-sectional studies showing an association between QCT bone density and fracture risk [59–68] but there is no consensus on whether QCT performs better than DXA in terms of predicting fracture risk. One prospective study of risk of hip fracture in men used QCT to show that bone density and morphology of the femoral neck were independent predictors of hip fracture [69]. Standard QCT generates images with in-plane voxel sizes of 300–500 mm and slice thickness of 1–3 mm and are therefore not adequate to assess trabecular bone microarchitecture, as trabecular thickness ranges from approximately 100 to 300 mm. High-resolution imaging with multislice spiral CT scanners (HRCTs) has been used to assess vertebral trabecular architecture (Fig. 2), achieving images with in-plane voxel size of 150–180 mm and slice thickness of 300–500 mm [70,71]. HRCT provides superior discrimination of vertebral fracture patients compared with BMD [70]. In monitoring changes in vertebral trabecular architecture following 1 year of teriparatide therapy, HRCT provided complementary information to that derived from densitometry [71]. Advantages to QCT are that it can be employed on standard clinical scanners with relatively short imaging times, providing robust assessment of geometry and volumetric bone density in trabecular and cortical compartments at sites most prone to fracture, although even the low radiation exposure is a concern to some. To define the clinical utility of this technique, additional data are needed on the ability of QCT-based measures to predict fracture risk prospectively and to monitor anti-fracture efficacy of drug interventions. High-resolution peripheral computed tomography (HR-pQCT) HR-pQCT measures bone density and trabecular and cortical microarchitecture, the distal radius and distal tibia with isotropic voxel size of w80 mm [72–80] (Fig. 3). This technique has excellent precision for both density (
M.L. Bouxsein, E. Seeman / Best Practice & Research Clinical Rheumatology 23 (2009) 741–753 745 Fig. 2. Multi-slice, high-resolution computed tomography images of the 12th thoracic vertebrae, showing image acquisition, identification of the region of interest, and segmentation of the vertebral trabecular bone. Images courtesy of Dr. Claus Glüer, University of Kiel. parameters measured by HR-pQCT in a standard patient analysis, including bone volume ratio, trabecular number, derived trabecular thickness, derived trabecular separation and cortical thickness, correlated well with measurements made with high-resolution micro-CT (i.e., 20-mm voxel size) [81]. Longitudinal HR-pQCT measurements indicate that whereas substantial cortical bone loss begins in middle life in women, it begins mainly after age 75 in men [78]. By contrast, trabecular bone loss begins early in adulthood in both women and men, such that approximately 40% of total life time trabecular bone loss occurs before age 50, as compared withe less than 15% for cortical bone. Cross-sectional studies have reported that microarchitecture measurements at the distal radius by HR-pQCT discriminate postmenopausal women with a history of fragility fracture from those who have not suffered a fracture, partly independent of BMD [72,75–77,82]. Preliminary reports have shown treatment-related changes in bone architecture as assessed by HR-pQCT, including increased cortical thickness following 1 year of denosumab [83] or strontium ranelate [84] therapy. As denosumab likely increases tissue mineral density due to its profound suppression of bone resorption [85] and strontium Fig. 3. High-resolution peripheral quantitative computed tomography image (voxel size ¼ 82 mm 3 ) of the distal radius (left) and distal tibia (right). Trabecular bone appears white, on a dark background.
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