Human trabecular bone microarchitecture can be assessed independently of density with second generation HR-pQCT

The second generation HR-pQCT scanner (XtremeCTII, Scanco Medical) can assess human bone microarchitecture of peripheral limbs with a 61 μm nominal isotropic voxel size. This is a marked improvement from the first generation HR-pQCT that had a nominal isotropic voxel size of 82 μm, which is at the limit to accurately determine the thickness of individual human trabeculae. We sought to determine the accuracy of a direct morphometric approach to measure trabecular bone microarchitecture with three-dimensional morphological techniques using second generation HR-pQCT, and to compare this with the approach currently applied by the first generation HR-pQCT scanner based on derived indices using ex vivo scans of human cadaveric radii. We also compared images acquired and resampled to mimic the first generation HR-pQCT with those obtained directly from the first generation HR-pQCT. We evaluated 20 human cadaveric radii and a micro-CT performance phantom using the first (XtremeCT, Scanco Medical) and second generation HR-pQCT scanner (XtremeCTII) and compared a patient evaluation (XCTII, 61 μm) with a high resolution ex vivo protocol (HR, 30μm). We generated 82 μm scans of the same specimens to mimic a first-generation HR-pQCT evaluation (XCTIM, 82 μm) and compared these with a first-generation patient evaluation (XCTI, 82 μm). A standard structural extraction approach was applied to both XCTII and HR evaluations for assessment of bone volume fraction (BV/TV), and a distance transform was used to assess trabecular number (Tb.N), trabecular thickness (Tb.Th) and trabecular separation (Tb.Sp). For XCTI and XCTIM evaluations we followed the manufacturer's standard procedure and assessed bone mineral density (BMD), Tb.N with a distance transform, and then derived bone volume ratio (BV/TV(d)), trabecular thickness (Tb.Th(d)) and separation (Tb.Sp(d)). The spatial resolution (10% MTF) was 142.2 μm for XCTI, 108.9 μm for XCTIM, 95.2μm for XCTII, and 55.9 μm for HR. XCTI and XCTIM provided strongly associated measurements of BMD and microarchitectural outcomes (R(2)>0.97), however there were systematic differences in all outcomes. The Tb.N was highly associated with HR by both XCTII (R(2)=0.93, mean error=-0.12 mm(-1)) and XCTIM (R(2)=0.98, mean error=0.25 mm(-1)). Also, both XCTII (R(2)=0.99, mean error=0.20mm) and XCTIM (R(2)=0.99, mean error=-0.18 mm) had Tb.Sp that were strongly related to HR. For Tb.Th, the XCTII was more closely related to HR (R(2)=0.94, mean error=0.04 mm) than the relatively weak XCTIM (R(2)=0.16, mean error=- 0.076 mm). We found that trabecular microarchitecture assessment following the XCTII direct morphometric approach accurately represented the HR data. In particular, the measure of Tb.Th was markedly improved for XCTII compared with the derived approach of XCTIM. These data support the application of analysis techniques in HR-pQCT that are analogous to those traditionally used for micro-CT to assess trabecular microarchitecture. The decreased dependence of structural outcomes on density provides a new, important opportunity to monitor human in vivo bone microarchitecture.