Effects of Intravenous Zoledronate on Bone Turnover and Bone Density Persist for at Least 11 Years in HIV-Infected Men

Abstract

Previously we reported the results of a 4‐year extension of a 2‐year randomized placebo‐controlled trial showing that the antiresorptive effects of two annual 4‐mg doses of zoledronate in HIV‐infected men persisted for at least 5 years after the second dose. We set out to determine whether the effects on BMD and bone turnover persist beyond 10 years. We invited all participants in the original trial known to be alive and living in New Zealand to attend an additional visit approximately 12 years after trial entry and 11 years after their second dose of study medication. The outcome measures were BMD at the lumbar spine, proximal femur, and total body, and markers of bone turnover. Twenty‐five of the 43 men originally enrolled in the trial attended the final visit, representing 25 of 31 (81%) participants alive and residing in New Zealand at the time. The average duration of follow‐up was 12.4 years. At the final visit, BMD remained higher in the zoledronate group than the placebo group (lumbar spine 3.7%, 95% CI, 0.1 to 7.3; total hip 3.7%, 95% CI, 1.2 to 6.2; femoral neck 5.0%, 95% CI, 2.1 to 7.9; total body 2.4%, 95% CI, 0.7 to 4.0), and the between‐group differences in BMD remained stable between 6 and 12 years. Serum CTx remained lower in the zoledronate group than the placebo group between 6 and 12 years and, at the final visit, was 45% lower (95% CI, 25 to 64) than the placebo group. P1NP was 26% (95% CI, 4 to 48) lower in the zoledronate group than the placebo group at the final visit. In summary, two annual 4‐mg doses of zoledronate have effects on bone turnover and BMD in men that persist for at least 11 years after the second dose. © 2019 American Society for Bone and Mineral Research.

Bisphosphonates after denosumab withdrawal reduce the vertebral fractures incidence

“…This finding is in keeping with the recent RCT of Sölling and co-authors ( 13) and points out the not fully satisfactory effectiveness of BPs treatment to prevent bone loss in patients treated with Dmab for more than 2.5 years. Up to now, the available studies, evaluated only the protective effect of a single ZOL infusion, in keeping with data showing that the effect of ZOL persist well beyond 12 months (19). Our study suggests that a single infusion of ZOL might not be sufficient to preserve BMD over time.…”

“…Among patients in Treated Group, 73 and 28 patients were treated with ZOL (single infusion, administered between 30 and 60 days after Dmab discontinuation) and ALN (once a week, immediately after Dmab discontinuation, for the whole follow up), respectively. We planned a single ZOL infusion on the basis of the evidence that the ZOL infusion effect persists well beyond 12 months (19) and in keeping with the ECTS position statement, which suggested to administer a single ZOL infusion (to be given possibly after Dmab discontinuation at the time of bone turnover increase) or to initiate oral bisphosphonates after Dmab withdrawal (20). During each consultation, patients treated with ALN were asked about their compliance (referred compliance ≥80% in al patients) and they were encouraged to contact our center in case of poor drug tolerability to evaluate ZOL infusion.…”

Bone Mineral Density and Bone Turnover 10 Years After a Single 5 mg Dose or Two 5-Yearly Lower Doses of Zoledronate in Osteopenic Older Women: An Open-Label Extension of a Randomized Controlled Trial

“…Currently, recommendations to prevent bone loss using zoledronate are for 2‐yearly administration of 5 mg doses. ( 16 ) The current work, together with results from another study in postmenopausal women ( 10 ) and a study in men with HIV, (9 ) demonstrates that bone loss in the axial skeleton is prevented for up to 10 years by a single dose of 5 mg zoledronate and 5‐yearly doses of either 1 or 2.5 mg zoledronate. If very infrequent zoledronate administration is shown to also reduce fracture risk, such treatment might be attractive to postmenopausal women as a preventive strategy and attractive to health care systems because it would facilitate fracture prevention at low cost.…”

“…Randomized trials conducted in postmenopausal women, (5,6) elderly women, (7) and men with HIV infection (8) indicate that 4 or 5 mg doses of zoledronate produce antiresorptive activity that persists for at least 5 years. Long-term follow-up of studies in men with HIV infection (9) or postmenopausal women (10) report that two doses of either 4 or 5 mg, respectively, prevent bone loss for 11 years. Data from a randomized trial in older women indicate that single doses of zoledronate of 1 and 2.5 mg exert antiresorptive effects that persist for 3 to 5 years.…”

Bone Health in People Living with HIV/AIDS: An Update of Where We Are and Potential Future Strategies

“…The protection provided by a single dose of zoledronic acid can last for 48 weeks from the onset of therapy with ARV [ 99 ]. Interestingly, Bolland et al showed that two annual 4 mg doses of zoledronate have positive effects on bone turnover and BMD in men, and these effects persist for at least 11 years after the second dose [ 100 ]. A single dose of zoledronic acid protects from BMD loss in PLWHIV without osteoporosis who start ARV [ 99 ].…”