BackgroundThe use of highly active antiretroviral therapy (HAART) has been associated with multiple metabolic complications whose pathogenesis is poorly understood at the present time.MethodsWe performed a cross-sectional analysis of whole-body, lumbar spine (L1–L4) and proximal femur bone mineral density in 112 male subjects (HIV-infected patients on HAART that included a protease inhibitor, HIV-infected patients not receiving a protease inhibitor and healthy seronegative adults) using dual energy x-ray absorptiometry.ResultsMen receiving protease inhibitors had a higher incidence of osteopenia and osteoporosis according to World Health Organization definitions: relative risk = 2.19 (95% confidence interval 1.13–4.23) (P= 0.02). Subjects receiving protease inhibitors had greater central : appendicular adipose tissue ratios than the other two groups (P< 0.0001). There was no relationship between the central : appendicular fat ratio and the lumbar spine or proximal femur bone mineral densityt- orz- scores, suggesting that osteoporosis and body fat redistribution are independent side effects of HAART.ConclusionsOsteopenia and osteoporosis are unique metabolic complications associated with protease inhibitor-containing potent antiretroviral regimens, that appear to be independent of adipose tissue maldistribution.