Is quantitative ultrasound dependent on bone structure? A reflection.

Trabecular bone plays a significant role in maintaining bone structural integrity. Its density is a significant determinant of bone strength and fracture risk, but there is still unexplained variance. It has been suggested that the ability to measure structural information will improve the estimation of bone strength and fracture risk. Quantitative ultrasound (QUS) is a mechanical wave that can be influenced by bone structure, in addition to bone mineral density (BMD). This article reviews the evidence in the literature supporting or refuting this assumption. Theoretically, the propagation of QUS is influenced by both structure and density of the medium. QUS measurement in vivo shows weak but significant association with axial BMD. However, the association becomes stronger when measured in vitro. Broadband ultrasound attenuation (BUA) exhibits a nonlinear relationship with density over a large density range. When cubes of cancellous bone are measured in the three orthogonal directions, both BUA and speed of sound (SOS) show significant anisotropy which mirrors mechanical anisotropy. QUS has also been shown to correlate significantly with structural parameters measured by histomorphometry. However, structure remains a significant predictor after adjustment for BMD mainly in bovine samples. Other studies using phantoms of bone samples have also demonstrated that QUS is dependent on structure. There is preliminary indication that fractal dimensions are significantly associated with QUS. The ultimate usefulness of structural dependence of QUS will be in its ability to improve bone strength estimation above and beyond density. There is ample evidence documenting the ability of QUS to predict bone strength in vitro. BMD is a significant predictor of bone strength and the additive value of structure in estimating bone strength is variable. Clinically, ultrasound of the calcaneus is measured in one direction (medio-lateral) and the structural variation in this direction may be limited. Nevertheless, QUS can provide useful additional information to that provided by axial BMD due in part to different precision and accuracy errors and to biological discordance. On the whole one could conclude that ultrasound attenuation is due to structural parameters and these variables are also dependent on density.