Recent studies suggest that bone loss occurs among HIV-infected women. This study examined the effects of reduced androgen levels, changes in weight, body composition, and menstrual dysfunction on bone mineral density (BMD) among 152 HIV-infected women characterized by normal weight (>90% ideal body weight [IBW], n = 124) and low weight (<or=90% IBW, n = 28) compared with 100 non-HIV-infected control subjects. BMD was assessed by dual x-ray absorptiometry, and free testosterone was assessed by equilibrium dialysis. Abdominal subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) were determined by computed tomography scan. A significant difference was seen in BMD between groups at the lumbar spine (0.92 +/- 0.02 g/cm vs. 1.01 +/- 0.01 g/cm vs. 1.07 +/- 0.01 g/cm; P < 0.0001), total hip (0.84 +/- 0.03 g/cm vs. 0.94 +/- 0.01 g/cm vs. 0.98 +/- 0.01 g/cm; P < 0.0001), and femoral neck (0.73 +/- 0.03 g/cm vs. 0.83 +/- 0.01 g/cm vs. 0.87 +/- 0.01 g/cm; P < 0.0001) (HIV-infected low-weight group, HIV-infected normal-weight group, and non-HIV-infected control subjects, respectively, for each comparison; mean +/- SEM). Among the HIV-infected subjects, lumbar BMD correlated with percent IBW (r = 0.37, P < 0.0001), total body lean mass (r = 0.43, P < 0.0001), total body fat mass (r = 0.35, P < 0.0001), and SAT (r = 0.41, P < 0.0001), but not VAT (r = 0.07, P = 0.417). Clinical risk factors for osteopenia and osteoporosis in the HIV population identified in univariate analysis included low free testosterone (<1.1 pg/mL [lower limit of the normal range of free testosterone for women] or 3.8 pmol/L; P = 0.0007), low weight (P = 0.014), and oligomenorrhea (P = 0.0006). In multivariate regression analysis, lean body mass was most significantly associated with BMD among those with HIV. These data demonstrate that BMD is reduced among HIV-infected women in association with low weight, reduced lean mass, reduced androgen levels, and abnormal menstrual function.