Tenofovir-associated bone density loss

Clinical observations have revealed a strong correlation between loss of bone density in HIV-infected individuals, particularly in conjunction with the antiretroviral drug tenofovir, a nucleotide analog that inhibits HIV reverse transcriptase. The most compelling correlations have been observed in clinical studies involving young children and adolescents. These obser-vations strongly suggest that bone density is being affected during active bone growth and development, implicating a role for tenofovir in bone loss. Here we discuss the literature and potential mechanisms for how tenofovir-associated bone loss may arise, which likely involves perturbation of cellular DNA synthesis and gene expression. Elucidation of the mechanism(s) involved in tenofovir-mediated bone loss will help in developing adjuvant therapies to reduce tenofovir-associated bone density loss.