In the Gilead 903 study, Gallant et al. demonstrated a net decrease in BMD of 1.2% at the lumbar spine in the TDF vs. d4T arms; bone loss in the TDF group occurred through weeks 24 and 48 in this cohort and stabilized through week 144. No additional bone loss was seen in a subgroup of Gilead 903 participants followed through 288 weeks ; participants in this open-label extension received supplemental calcium and vitamin D. In the more recent ASSERT trial, Stellbrink et al. reported a net 0.8% and 1.7% decrease in BMD at the lumbar spine and total hip respectively, when comparing the tenofovir-emtricitabine vs. the abacavir-lamivudine group. In this European cohort, bone loss in the TDF group stabilized at week 24 at the lumbar spine but ongoing loss occurred through week 48 at the total hip. Given the relatively short duration of follow-up in most these studies, longer term BMD data are required to better characterize the long-term effects of TDF on BMD. Current PrEP trials are testing tenofovir-based regimens in over 20,000 HIV-uninfected LDN-193189 supplier individuals at risk for HIV infection. Several of these trials are measuring BMD in a subset of study participants, including the iPrEx trial, a phase 3 efficacy trial of emtricitabine-tenofovir in MSM globally. Given our findings, we encourage other PrEP trials to include DEXA monitoring when logistically possible to better characterize the baseline prevalence of low BMD in different target populations for PrEP and the prevalence of risk factors for low BMD, and determine the magnitude and trajectory of BMD loss associated with ARV use for prevention. These data may help identify individuals who are at risk for low BMD or bone loss with PrEP use and guide clinical decision making on whether screening for low BMD may be warranted prior to initiation of PrEP. The clinical significance of TDF-associated BMD loss, including whether fracture risk is increased, is currently unknown. In this study, we observed 6 fractures in the TDF group vs. 4 in the placebo group, although this study was not designed or Abmole Z-VAD-FMK powered to detect differences in fracture rates between arms. All fractures were trauma-related and assessed as unrelated to study drug. In the Gilead 903 study, 16 patients (11 in the stavudine group vs. 5 in the tenofovir group) developed fractures through 144 weeks, and almost all were related to trauma. However, there have been case reports of fractures during TDF therapy, in the setting of proximal renal tubule dysfunction. Additional follow-up in larger cohorts is needed to determine whether extended use of TDF increases fracture risk. Our study is subject to some limitations. First, this study was conducted in only 1 site (San Francisco) in HIV-uninfected men, the majority of whom were white. Additional studies are being conducted in different settings and in other populations, including HIV-uninfected women, and will determine whether our findings can be generalized. Second, we had a relatively small sample size, precluding multivariable analysis of factors associated with low BMD at baseline, as well as analyses to identify any subgroups at higher risk for BMD loss during TDF PrEP use.