We investigated whether quantitative ultrasound (QUS) parameters are associated with bone structure. In an in vitro study on 20 cubes of trabecular bone, we measured broadband ultrasound attenuation (BUA) and two newly defined parameters--ultrasound velocity through bone (UVB) and ultrasound attenuation in bone (UAB). Bone mineral density (BMD) was measured by dual X-ray absorptiometry (DXA) and bone structure was assessed by microcomputed tomography (microCT) with approximately 80 microns spatial resolution. We found all three QUS parameters to be significantly associated with bone structure independently of BMD. UVB was largely influenced by trabecular separation, UAB by connectivity, and BUA by a combination of both. For a one standard deviation (SD) increase in UVB, a decrease in trabecular separation of 1.2 SD was required compared with a 1.4 SD increase in BMD for the same effect. A 1.0 SD increase in UAB required a reduction in connectivity of 1.4 SD. Multivariate models of QUS versus BMD combined with bone structure parameters showed squared correlation coefficients of r2 = 0.70-0.85 for UVB, r2 = 0.27-0.56 for UAB, and r2 = 0.30-0.68 for BUA compared with r2 = 0.18-0.58 for UVB, r2 < 0.26 for UAB and r2 < 0.13 for BUA for models including BMD alone. QUS thus reflects bone structure, and a combined analysis of QUS and BMD will allow for a more comprehensive assessment of skeletal status than either method alone.