Context: In HIV-infected men, the antiresorptive effects of zoledronate persist for at least 2 yr after the second annual dose.
Objective: Our objective was to determine the duration of action of zoledronate in men.
Design and setting: This was 4-yr extension of a 2-yr, double-blind, randomized, placebo-controlled trial at an academic research center.
Participants: Participants included 43 HIV-infected men with bone mineral density (BMD) T score below -0.5, 35 of whom entered the extension study.
Intervention: Intervention was annual administration of 4 mg iv zoledronate or placebo at baseline and 1 yr and no intervention subsequently.
Main outcome measures: We evaluated changes in the bone turnover markers, serum osteocalcin and serum C-telopeptide (CTx), and changes in BMD at the lumbar spine, total hip, and total body.
Results: There was no time × treatment interaction between 1 and 5 yr after the second zoledronate dose for osteocalcin or CTx (P > 0.4) or any BMD site (P > 0.7). Between 1 and 5 yr after the second dose, on average, osteocalcin was 41% lower (95% confidence interval = 19-62%; P < 0.001), CTx 52% lower (33-71%; P < 0.001), lumbar spine BMD 3.7% greater (0.3-7.0%; P = 0.03), total hip BMD 2.3% greater (0.3-4.3%; P = 0.02), and total body BMD 2.5% greater (0.8-4.1%; P = 0.004) in the zoledronate group than the placebo group. Five years after the second dose, the between-groups differences were 38% (13-62%) for osteocalcin, 49% (20-77%) for CTx, 3.5% (0.7-6.7%) for lumbar spine BMD, 3.4% (1.4-5.4%) for total hip BMD, and 1.6% (0.2-3.1%) for total body BMD.
Conclusion: The effects of two annual 4-mg doses of zoledronate in men persist for at least 5 yr after the second dose. Larger trials assessing the antifracture efficacy of less frequent dosing of zoledronate are justified.