SummaryCurrently, the accepted "gold standard" method for bone mineral density (BMD) measurement and osteoporosis diagnosis is dual-energy X-ray absorptiometry (DXA). However, actual DXA effectiveness is limited by several factors, including intrinsic accuracy uncertainties and possible errors in patient positioning and/or post-acquisition data analysis. DXA employment is also restricted by the typical issues related to ionizing radiation employment (high costs, need of dedicated structures and certified operators, unsuitability for population screenings). The only commercially-available alternative to DXA is represented by "quantitative ultrasound" (QUS) approaches, which are radiation-free, cheaper and portable, but they cannot be applied on the reference anatomical sites (lumbar spine and proximal femur). Therefore, their documented clinical usefulness is restricted to calcaneal applications on elderly patients (aged over 65 y), in combination with clinical risk factors and only for the identification of healthy subjects at low fracture risk. Literature-reported studies performed some QUS measurements on proximal femur, but their clinical translation is mostly hindered by intrinsic factors (e.g., device bulkiness). An innovative ultrasound methodology has been recently introduced, which performs a combined analysis of B-mode images and corresponding "raw" radiofrequency signals acquired during an echographic scan of the target reference anatomical site, providing two novel parameters: Osteoporosis Score and Fragility Score, indicative of BMD level and bone strength, respectively. This article will provide a brief review of the available systems for osteoporosis diagnosis in clinical routine contexts, followed by a synthesis of the most promising research results on the latest ultrasound developments for early osteoporosis diagnosis and fracture prevention.