Accelerated bone mineral loss in HIV-infected patients receiving potent antiretroviral therapy

Abstract

Background: The use of highly active antiretroviral therapy (HAART) has been associated with multiple metabolic complications whose pathogenesis is poorly understood at the present time.

Methods: We 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.

Results: Men 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 density t- or z- scores, suggesting that osteoporosis and body fat redistribution are independent side effects of HAART.

Conclusions: Osteopenia and osteoporosis are unique metabolic complications associated with protease inhibitor-containing potent antiretroviral regimens, that appear to be independent of adipose tissue maldistribution.

Fig. 1

Lumbar spine bone mineral density (BMD) t-scores for the 112 men included in this study. The box represents the inter-quartile range, the thick line the median and the thin lines the range of the t-scores. The median lumbar spine BMD (P = 0.002) and the t-score for the HIV-positive patients on protease inhibitors (HIV+ PI+) group (P = 0.02) were lower than the other two groups. Controls, healthy, uninfected subjects; no PI HIV+, HIV-positive patients not taking protease inhibitors.

Fig. 2

HIV-positive patients taking protease inhibitors (HIV+ PI+) had significantly lower bone mineral density (BMD) z-scores in the neck (P = 0.08), trochanteric (P = 0.01) and Ward’s triangle (P = 0.09) regions of the proximal femur than the other two groups (Kruskal–Wallis test). Controls, healthy, uninfected subjects; no PI HIV+, HIV-positive patients not taking protease inhibitors.

Fig. 3

Patients on protease inhibitors had greater central : appendicular adipose tissue ratios than the other two groups (P 0.0001). Controls, healthy, uninfected subjects; PI+ HIV+, HIV-positive patients taking protease inhibitors; no PI HIV+, HIV-positive patients not taking protease inhibitors.