Bone Quality Beyond DXA in People Living with HIV: A Systematic Review of HR-pQCT, TBS, Microindentation, and...

Background and Objectives: People living with HIV (PLWH) have excess fragility fractures not fully explained by areal DXA. We reviewed bone "quality" in PLWH-microarchitecture, estimated strength, tissue-level properties-and vertebral fractures (VFs). Methods: PRISMA-conform systematic review (2000-2025) of randomized, cohort, and cross-sectional studies assessing HR-pQCT (±finite-element analysis), trabecular bone score (TBS), impact microindentation (BMSi), femoral QCT/MRI, and VF imaging (DXA-VFA or radiography). Risk of bias used ROBINS-I (non-randomized) and RoB 2 (randomized/switch). No meta-analysis was performed due to clinical/methodological heterogeneity; evidence was synthesized narratively per SWiM. Results: Fourteen studies met criteria. HR-pQCT showed cortical/trabecular deficits with lower finite-element-estimated strength in PLWH. BMSi was 3-4 units lower; it declined after ART initiation but improved after TDF→TAF switch. TBS was modestly lower and reclassified risk when BMD was non-osteoporotic. VF prevalence was 12-25% and frequently occurred at non-osteoporotic BMD. Signals aligned with modifiable risks (smoking, glucocorticoids) and specific ART exposures. Conclusions: Beyond DXA, PLWH exhibit quantifiable decrements in microarchitecture, estimated strength, and tissue-level properties alongside a meaningful VF burden. TBS and VFA are pragmatic, scalable adjuncts to refine risk; HR-pQCT/BMSi add mechanistic value in research/tertiary settings. Prospective studies linking these metrics to incident fractures are warranted.