Multimodal Bone Fragility Profiling in People Living with HIV: Trabecular Bone Score, Calcaneal Quantitative Ultrasound, and Sarcopenia Screening

<i>Background and Objectives:</i> Bone fragility in people living with HIV (PLWH) reflects both reduced bone mineral density (BMD) and impaired microarchitecture, while functional decline may further amplify fracture vulnerability. This study evaluated whether adding a pragmatic sarcopenia screen improves bone fragility characterization beyond DXA-BMD, trabecular bone score (TBS), calcaneal quantitative ultrasound (QUS), and biomarkers, and explored the relationship between tenofovir disoproxil fumarate (TDF) exposure and microarchitectural impairment. <i>Materials and Methods:</i> In this single-center cross-sectional study at Victor Babeș University of Medicine and Pharmacy Timișoara, 98 adults on stable ART underwent DXA (T-scores), lumbar TBS (reported as TBS × 100), calcaneal QUS (SOS/BUA), and bone turnover markers (CTX, P1NP, 25(OH)D). Sarcopenia screening used handgrip strength and 4 m gait speed. Associations were tested using group comparisons, correlations, and multivariable modeling for degraded TBS (TBS × 100 < 124.0). <i>Results:</i> Sarcopenia screen-positive participants (<i>n</i> = 28) had lower TBS (123.8 vs. 127.7, <i>p</i> = 0.02), lower lumbar T-score (-1.7 vs. -1.2, <i>p</i> = 0.014), lower SOS (1523.3 vs. 1548.8 m/s, <i>p</i> = 0.002), and higher CTX (0.6 vs. 0.4 ng/mL, <i>p</i> < 0.001), with less frequent viral suppression (60.7% vs. 85.7%, <i>p</i> = 0.006). With >5 years TDF exposure (<i>n</i> = 28), degraded TBS prevalence was 82.1% vs. 40.0% in never-exposed (<i>p</i> = 0.001), alongside lower TBS (123.1 vs. 129.8, <i>p</i> < 0.001) and higher CTX (0.6 vs. 0.4 ng/mL, <i>p</i> < 0.001). Viral suppression independently reduced odds of degraded TBS (aOR 0.3, 95% CI 0.1-0.9; <i>p</i> = 0.034). <i>Conclusions:</i> In PLWH, prolonged TDF exposure and functional impairment co-occur with worse densitometric and microarchitectural profiles; viral suppression shows an independent protective association with microarchitecture.