Tenofovir disoproxil fumarate (TDF) is a widely used pharmacological agent for the treatment of human immunodeficiency virus infection. While prolonged exposure to TDF has been associated with a decrease in bone mineral density (BMD) and increased fracture risk, limited discussion exists on its effects on various aspects of bone quality. This scoping review aims to provide a comprehensive overview of the impact of TDF on bone quality beyond BMD. A literature search was conducted using the PubMed and Scopus databases to identify studies investigating the effects of TDF on bone quality. Original research articles written in English, irrespective of study type or publication year, were included in the review. Seven articles met the inclusion criteria. Findings indicate that prolonged exposure to TDF adversely affects bone microarchitecture and strength, impeding fracture healing and skeletal microdamage repair. The observed effects suggest a complex interplay involving bone cell signalling, cytokines and bone remodelling processes as potential mechanisms underlying TDF’s impact on bone quality. As a conclusion, TDF impairs bone remodelling and microarchitecture by influencing dynamic bone cell behaviour and signalling pathways. Future studies should delve deeper into understanding the intricate negative effects of TDF on bone and explore strategies for reversing these effects.

Background/Objectives: Individuals living with human immunodeficiency virus (HIV) receiving tenofovir-based antiretroviral therapy (ART) are at increased risk of bone loss. Dual-energy X-ray absorptiometry (DXA), the gold standard for determining bone mineral density (BMD), has limited accessibility. Calcaneal quantitative ultrasound (QUS) is an alternative screening tool for bone health, but its performance needs validation. The study aims to compare the performance of QUS between men with HIV on tenofovir-based ART and uninfected men. Methods: A cross-sectional study involving 52 men with HIV on tenofovir-based ART and 42 uninfected men was performed. Their bone health status was determined using DXA (lumbar spine and femoral neck) and QUS (calcaneus). The performance of QUS in identifying individuals with low BMD (DXA T-score < −1) was evaluated using receiver-operating characteristic curve analysis. Results: The HIV-ART group showed significantly lower QUS indices compared to the non-HIV-ART group (p < 0.05). The performance of QUS in identifying individuals with low BMD was poor in the HIV-ART group (p > 0.05), but moderate in the non-HIV-ART group (p < 0.05). After optimising the cutoffs, the performance of QUS was improved in the non-HIV-ART group but not in the HIV-ART group. Conclusions: QUS was not effective in identifying individuals with low BMD in men with HIV on ART. Its utility as a standalone screening tool in this population may be limited. Additional or more sensitive methods should be prioritised for bone health screening.