High-resolution peripheral quantitative computed tomography (HR-pQCT) is a low-dose three-dimensional imaging technique, originally developed for in vivo assessment of bone microarchitecture at the distal radius and tibia in osteoporosis. HR-pQCT has the ability to discriminate trabecular and cortical bone compartments, providing densitometric and structural parameters. At present, HR-pQCT is mostly used in research settings, despite evidence showing that it may be a valuable tool in osteoporosis and other diseases. This review summarizes the main applications of HR-pQCT and addresses the limitations that currently prevent its integration into routine clinical practice. In particular, the focus is on the use of HR-pQCT in primary and secondary osteoporosis, chronic kidney disease (CKD), endocrine disorders affecting bone, and rare diseases. A section on novel potential applications of HR-pQCT is also present, including assessment of rheumatic diseases, knee osteoarthritis, distal radius/scaphoid fractures, vascular calcifications, effect of medications, and skeletal muscle. The reviewed literature seems to suggest that a more widespread implementation of HR-pQCT in clinical practice would offer notable opportunities. For instance, HR-pQCT can improve the prediction of incident fractures beyond areal bone mineral density provided by dual-energy X-ray absorptiometry. In addition, HR-pQCT may be used for the monitoring of anti osteoporotic therapy or for the assessment of mineral and bone disorder associated with CKD. Nevertheless, several obstacles currently prevent a broader use of HR-pQCT and would need to be targeted, such as the small number of installed machines worldwide, the uncertain cost-effectiveness, the need for improved reproducibility, and the limited availability of reference normative datasets.
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