PURPOSE OF REVIEW: With continued improvements to the antiviral efficacy and tolerability of antiretroviral therapy, long-term safety of antiretroviral therapy has become paramount. Low bone mineral density and fragility fractures are more common in HIV-infected individuals than in the general population. The aims of this review are to describe potential mechanisms underlying the adverse effects of tenofovir on bone, clinical studies of tenofovir disoproxil fumarate (TDF) and bone, and more recent bone data on tenofovir alafenamide. RECENT FINDING: Several studies have demonstrated an approximately 1-3% greater bone mineral density loss with TDF compared with other agents. Recent studies with tenofovir alafenamide have shown improved bone (and renal) safety with similar virologic efficacy when compared to TDF. SUMMARY: Given these findings, TDF-containing regimens may be gradually replaced with non-TDF containing regimens for the treatment of HIV infection, especially in those at higher risk for fragility fracture.