BACKGROUND: Perinatally HIV-infected (PHIV) children and adolescents with low bone mineral density (BMD) may be at higher risk of osteoporosis and fractures in later life than their uninfected peers. Bisphosphonate therapy has been shown to reduce fractures in adults with osteoporosis, but has not been formally studied in HIV-infected youth.

METHODS: Fifty-two PHIV 11- < 25 years of age with low lumbar spine (LS) BMD (Z-score < -1.5) were randomized to receive once-weekly alendronate or placebo in a double-blind cross-over study designed to assess the safety and efficacy of 48 and 96 weeks of alendronate in the US and Brazil (ClinicalTrials.gov # NCT000921557). All participants received daily calcium carbonate and vitamin D supplementation and were asked to engage in regular weight-bearing exercise. Safety and efficacy are summarized for the initial 48 weeks of the trial.

RESULTS: Grade > /= 3 abnormal laboratory values, signs, or symptoms developed in 5 of 32 (16%) participants on alendronate and 2 of 18 (11%) on placebo (p > 0.99). No cases of jaw osteonecrosis, atrial fibrillation, or non-healing fractures were reported. Mean increases (95% confidence interval) in LS BMD over 48 weeks were significantly larger on alendronate [20% (14%, 25%)] than placebo [7% (5%, 9%), p < 0.001]. Similar improvements were seen for whole body BMD.

CONCLUSIONS: In this small study in PHIV children and adolescents with low LS BMD, 48 weeks of alendronate was well-tolerated, showed no safety concerns, and significantly improved LS and whole body BMD compared to participants on vitamin D/calcium supplementation and exercise alone.