In comparing the TDF vs. placebo groups, median age, race/ethnicity, smoking, alcohol and recreational drug use, concomitant Abmole WZ8040 medication use, dietary calcium and vitamin D intake, exercise patterns, and baseline laboratory Foretinib c-Met inhibitor parameters did not differ significantly between the 2 groups. Mean weight, total fat mass, and body mass index (BMI), but not fat-free mass, were slightly but significantly higher in the TDF vs. placebo group. Prevalence of low BMD by this measure was significantly higher than expected (20 vs. 4.8 cases; p,0.001) under the standard normal assumption. Three individuals had low BMD at 2 anatomic sites, 2 at the total hip and femoral neck, and 1 at the total spine and femoral neck. In univariate analysis (table 2), men who used amphetamines (OR =5.9, p,0.01) or inhalants (OR = 4.6, p = 0.02) were significantly more likely to have low BMD at baseline. Men who reported supplemental calcium/vitamin D use (59%) were less likely to have low BMD (OR = 0.26, p = 0.009). Because there were only 12 low BMD cases among the 196 men with complete baseline covariate data, multivariable analysis of low BMD was not performed. At 2 of 3 anatomic locations, TDF exposure resulted in a statistically significant decrease in BMD relative to baseline when compared to the pre-treatment/placebo group. In the intent-totreat analysis, there was a 1.1% mean net decrease in BMD in the TDF vs. pre-treatment/placebo group at the femoral neck (95% CI 0.4-1.9%, p= 0.004) and an 0.8% net decline at the total hip (95% CI 0.3-1.3%, p = 0.003); at the L2-L4 spine, there was nonsignificant evidence for an adverse effect (0.7% decline, 95% CI 20.1-1.5%, p = 0.11). After censoring follow-up for individuals taken off study drug due to a.5% drop in BMD or low BMD on a follow-up scan, the net loss was 1.2% (p = 0.002), 0.8% (p = 0.003), and 0.9% (p= 0.039) for the femoral neck, total hip, and L2-L4 spine respectively. Results were similar after adjustment for baseline BMD, BMI, creatinine clearance, race, age, and baseline inhalant and amphetamine use. Trajectories of BMD change over time by anatomic site are shown in Figure 3. Declines in BMD in the TDF group were most prominent in the first 12 months of treatment in the immediate arm, with similar decreases seen in the delayed arm upon initiation of TDF during the 9 to 24 month period.