Context: Recent studies have reported low bone mineral density (BMD) in HIV-infected patients. Annual intravenous administration of 4mg zoledronate has been shown to increase BMD and suppress bone turnover in postmenopausal women.

Objective: To determine whether annual administration of 4mg zoledronate will increase BMD in HIV-infected men receiving highly active anti-retroviral therapy (HAART)

Design: Two-year, randomized, placebo-controlled trial.

Setting: Clinical research center

Participants: 43 HIV-infected men treated with HAART for at least 3 months, with BMD T score <-0.5.

Intervention: Annual intravenous administration of 4mg zoledronate or placebo. All participants took 400mg/day calcium and 1.25mg/month vitamin D

Measurements: BMD at the lumbar spine, total hip and total body, and bone turnover markers.

Results: At the lumbar spine, BMD increased by 8.9% over two years in the zoledronate group compared to an increase of 2.6% in the control group (P<0.001). At the total hip, BMD increased by 3.8% over two years in the zoledronate group compared to a decrease of 0.8% in the control group (P<0.001). At the total body, BMD increased by 2.3% over two years compared to a decrease of 0.5% in the control group (P<0.001). Urine N-telopeptide fell by 60% at 3 months in the zoledronate group and thereafter remained stable.

Conclusions: Annual administration of zoledronate is a potent and effective therapy for the prevention or treatment of bone loss in HIV-infected men. The current data provide the first trial evidence of the BMD effects of annual zoledronate beyond 1 year in any population, as well as being the first reported trial in men.