Context: HIV infection has been associated with low bone mineral density (BMD) in many cross-sectional studies, although longitudinal studies have not demonstrated accelerated bone loss. The cross-sectional studies may have been confounded by the failure to control for low body weight in HIV-infected patients.

Objective: To determine whether low body weight might explain the association of HIV infection with low BMD.

Data Sources: MEDLINE and EMBASE were searched for English language studies published from 1966 to March 2007, and conference abstracts prior to 2007 were hand-searched.

Study Selection: All studies reporting BMD and weight or body mass index in adult patients with HIV and a healthy age- and sex-comparable control group were included. Nine of 40 identified studies and one of 68 identified abstracts were eligible.

Data Synthesis: We adjusted for the between-groups weight differences using regression coefficients from published cohorts of healthy men and women. On average, HIV-infected patients were 5.1 kg (95% CI -6.8,-3.4; P < 0.001) lighter than controls. At all skeletal sites, unadjusted BMD was lower, by 4.4–7.0%, in the HIV-infected groups than the controls (P < 0.01). After adjustment for body weight, residual between-groups differences in BMD were small (2.2–4.7%) [lumbar spine: -0.02 (95% CI -0.05,0.01) g/cm², P = 0.12; total hip: -0.02 (-0.04,0.00) g/cm², P = 0.031; femoral neck: -0.04 (-0.07,-0.01) g/cm², P = 0.013; total body: -0.03 (-0.07,0.01) g/cm², P = 0.11).

Conclusion: HIV-infected patients are lighter than controls and low body weight may largely account for the high prevalence of low BMD reported in HIV-infected patients. However, in the setting of current treatment practice, HIV infection per se is not a risk factor for low BMD.