Abstract / Summary
Background Dual-energy X-ray absorptiometry (DXA) is currently the clinical reference standard for osteoporosis diagnosis and fracture risk assessment. However, it provides only a partial description of bone strength and has practical limitations related to accessibility and ionizing radiation. Over the past three decades, quantitative ultrasound (QUS) technologies have evolved from empirical heel-based measurements to advanced imaging approaches capable of characterizing cortical bone structure and material properties. Objectives To review the development of bone ultrasound technologies, summarize their clinical evidence for fracture risk assessment, and discuss the opportunities and challenges of emerging ultrasound-based approaches. Findings First-generation calcaneal QUS devices demonstrate fracture prediction comparable to peripheral DXA in large prospective studies and remain valuable for fracture risk assessment, particularly where DXA is unavailable or repeated X-ray examinations are undesirable. Their broader clinical adoption was limited mainly by device-specific algorithms, lack of standardization, and the absence of universally accepted diagnostic thresholds. Newer ultrasound technologies extend assessment to clinically relevant skeletal sites, including the hip and spine, or directly quantify cortical bone structure and material properties at peripheral sites. Radiofrequency echographic multi-spectrometry (REMS) has shown encouraging results in cross-sectional and prospective studies but relies on proprietary reference models and algorithms that require greater transparency and independent validation. Second-generation technologies, including cortical backscatter analysis (CortBS) and refraction-corrected imaging, provide quantitative measurements of cortical thickness, porosity-related microstructure, wave speed, attenuation and other biomechanical biomarkers in physical SI units, enabling independent validation and multiparametric fracture-risk modeling. However, until now these technologies have only been validated ex-vivo on human cadaver bones and in-vivo in small exploratory cross-sectional fracture discrimination studies. Multicenter cross-sectional and prospective studies are underway to create reference data and to establish their value for fracture risk prediction. Conclusions Bone ultrasound has progressed from an empirical screening tool to a family of quantitative technologies capable of assessing complementary aspects of bone quality and quantity. Calcaneal QUS is currently the only technology with an established guideline-recognized role in fracture risk assessment. Prospective multicenter fracture risk prediction studies, as well as technical standardization and transparent validation studies showing cross-vendor reproducibility and independent replication are now required to define the clinical role of newer ultrasound technologies and support their integration into future osteoporosis management and clinical routine use.