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OBJECTIVES Although bone density has been previously investigated in HIV-infected men, little is known regarding bone density in HIV-infected women. METHODS AND DESIGN Bone density was measured by dual-energy X-ray absorptiometry in 84 ambulatory, HIV-infected females and 63 healthy female control subjects similar in age (41 +/-1 versus 41+/- 1 years, P = 0.83), body mass index (26.0 +/- 0.6 versus 27.0 +/- 0.5 kg/m, P = 0.44) and racial background (% non-Caucasian, 61 versus 51%; P = 0.24, HIV-infected versus control). RESULTS Lumbar spine (1.02+/- 0.02 versus 1.07 +/- 0.02 g/cm, P = 0.03) and total hip (0.93 +/-0.01 versus 0.99 +/- 0.01 g/cm, P = 0.004) bone density were reduced in HIV-infected compared with control subjects. Osteopenia was demonstrated in 54 versus 30% (P = 0.004) of HIV-infected versus control subjects and was 2.5 times more likely in a multivariate model accounting for age, race, menstrual function and body mass index. Urinary N-telopeptides of type 1 collagen (NTx) (39.6 +/- 3.5 versus 29.9 +/- 2.0 nM/mM urine creatinine, P = 0.03) and osteoprotegerin (4.76 +/- 0.23 versus 3.39 +/- 0.17 pmol/l, P < or = 0.0001) were increased in HIV-infected compared with control subjects. Among the HIV-infected women, bone density correlated with weight (r = 0.41, P < 0.001) and inversely with urinary NTx (r = -0.28, P = 0.01). Bone density did not differ by current or past protease inhibitor, nucleoside reverse trancriptase inhibitor, or non-nucleoside reverse transcriptase inhibitor exposure. CONCLUSIONS HIV-infected women demonstrate reduced bone density. Altered nutritional status, hormonal function and body composition may contribute to lower bone density in HIV-infected women. Consideration should be given to testing bone density in HIV-infected women with risk factors for osteopenia.