Osteopenia in HIV-infected women prior to highly active antiretroviral therapy

Abstract

Background and objectives: Multiple endocrine and metabolic consequences of human immunodeficiency (HIV) infection exist that alter bone metabolism in patients with acquired immune deficiency syndrome (AIDS). Osteopenia in AIDS patients has been associated with antiretroviral therapy particularly with protease inhibitors. However, there is very little data on bone metabolism in female subjects with AIDS prior to highly active antiretroviral therapy.

Methods: Bone mineral density (BMD) was assessed by dual-energy X-ray absorptiometry (DEXA) in 50 HIV-infected female outpatients (mean age 37 years) both in the lumbar spine and the Ward's triangle of the left hip. Additional parameter assessed were demographics, smoking, CD4 counts, fasting metabolic parameters and biochemical markers of bone metabolism. None of the patients received reverse transcriptase inhibitors or protease inhibitors, vitamin D or calcium-supplementation.

Results: The serum levels of parathyroid hormone and 1,25-dihydroxyvitamin D (1,25(OH2)D) were significantly reduced compared to 50 age-matched female healthy controls. Urinary calcium and pyridinium crosslinks-excretion corrected for creatinine excretion were elevated (P<0.01) and were likewise significantly correlated with the loss of CD4 cells (P<0.05). Serum osteocalcin was significantly lowered (P<0.01). Reduced BMD of the lumbar spine (t -score <-2.5 SD below normal) was found in seven patients (14%) and osteopenia (t -score -1.0 to -2.5 SD below normal) was diagnosed in 31 (62%). No patient had a fracture since being infected with HIV. The BMD was reduced both in lumbar spine and the hip measured in the left Ward's triangle. There were significant positive correlation between the CD4 counts and 1,25(OH2)D (P<0.05). Neither the CD4 counts nor the duration of disease correlated with BMD. The reduced bone formation rate was linked to progressive loss of CD4-cell count.

Conclusion: Osteopenia in HIV-infected female subjects is commonly manifested both in lumbar spine and Ward's triangle of the hip. There is a dissociation between lowered markers of bone formation rate and the increased bone resorption expressed as elevated urinary crosslinks and calcium excretion. Furthermore, the decreased levels of 1,25(OH2)D may contribute to a negative calcium balance and inhibition of bone formation. Our results suggest that further research is necessary to determine, whether low levels of 1,25(OH2)D lead to an accelerated inflammatory process in AIDS, since 1,25(OH)2D is known as an endogenous immune modulator suppressing formation of activated T cells and cell proliferation.