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Zoledronate Improves Bone Loss in People with HIV

Research indicates that people with HIV are more susceptible to bone loss -- osteopenia or the more severe osteoporosis -- compared with HIV negative individuals. Some studies have reported rates as high as 50%-70%, but it is not yet clear whether this is due to HIV infection itself, immune dysfunction, systemic inflammation, antiretroviral therapy, or some combination of factors.

In a study published in the January 2, 2009 issue of AIDS, Jeannie Huang from the University of California at San Diego and colleagues evaluated the safety and efficacy of zoledronate (various brand names including Reclast and Zometa) for the treatment of HIV-associated bone mineral loss. This bisphosphonate drug -- which works by reducing bone resorption (metabolic reclaiming of bone minerals) -- is currently FDA-approved for treatment of osteoporosis and prevention of bone fractures in post-menopausal women and people with certain types of cancer.

This double-blind controlled trial included 27 HIV positive patients (27 men, 3 women; mean age 48 years) with osteopenia or osteoporosis, as indicated by reduced bone mineral density of the lumbar (lower) spine or hip.

Participants were randomly assigned (1:1) to receive a single 5 mg intravenous dose of zoledronate or placebo. (An oral of formulation of zoledronate is also available, but it can cause gastrointestinal side effects.) All patients also received daily calcium and vitamin D supplements; those who started with a vitamin D deficiency were brought up to a normal level before receiving zoledronate.

Baseline characteristics, including sex, race/ethnicity, body composition, and bone density, were similar in treatment and placebo arms, though zoledronate recipients had a significantly higher average CD4 count (663 vs 384 cells/mm³). Participants had well controlled HIV disease overall; all but one were on stable antiretroviral therapy and 93% had HIV viral load < 400 copies/mL. At study entry, median T-scores (a measure of bone density) were -1.7 for the lumbar spine and -1.4 for the hip.

Participants were followed for 12 months. Lumbar spine and hip bone density was assessed using dual energy X-ray absorptiometry (DEXA) at baseline and at 6 and 12 months post-treatment. Biomarkers of bone metabolism (osteocalcin and N-telopeptides and C-terminal telopeptides of type I collagen) were measured at baseline, 2 weeks, and 3, 6, 9, and 12 months.

Results

• Bone density -- measured as both absolute changes and sex-adjusted T-scores -- significantly improved in the zoledronate arm compared with minimal changes in the placebo arm:
  • Lumbar spine: significant increase in zoledronate recipients vs slight increase in placebo recipients (+3.7% vs +0.7%; P = 0.04);
  • Hip: significant increase in zoledronate recipients vs small decrease in placebo recipients (+3.2% vs -1.8%; P = 0.016).
• In the zoledronate arm, lumbar spine density peaked at 6 months, but hip density continued to increase between 6 and 12 months.
• Bone resorption biomarkers significantly decreased over the study period in the zoledronate arm compared with the placebo arm.
• Bone-related outcomes were not associated with body mass index, CD4 cell count, or HIV viral load.
• Zoledronate was generally well tolerated.
• No acute infusion reactions were observed.
• 1 participant developed uveitis (inflammation of the uvea, or middle layer of the eye including the iris), a recognized complication of zoledronate, which responded to topical steroid therapy.

Based on these findings, the study authors concluded, "In this small study, annual zoledronate appears to be a well tolerated and effective therapy for HIV-associated bone loss."

"Its combination of good tolerability, low medication burden, and effectiveness make zoledronate an excellent candidate to treat a common complication of chronic therapy for a life-threatening disease," they wrote.

They acknowledged, however, that further study is needed, especially in HIV positive women, who were underrepresented in this trial, given that women are more prone to bone loss than men in the general HIV negative population.

1/20/09

Reference

J Huang, L Meixner, S Fernandez, and others. A double-blinded, randomized controlled trial of zoledronate therapy for HIV-associated osteopenia and osteoporosis. AIDS 23(1): 51-57. January 2, 2009.