Treatment with Zoledronate Subsequent to Denosumab in Osteoporosis: a Randomized Trial

Abstract

Discontinuing denosumab is associated with bone loss and possibly increased fracture risk. We investigated if treatment with zoledronate (ZOL) could prevent bone loss and if the timing of the ZOL infusion influenced the outcome. We report on a 2-year randomized, open label, interventional study including 61 patients with osteopenia, discontinuing denosumab after 4.6 ± 1.6 years. We administrated ZOL 6 months (6M group, n = 20) or 9 months (9M group, n = 20) after the last denosumab injection or when bone turnover had increased (OBS group, n = 21). We monitored the patients with DXA and bone turnover markers. Our primary endpoints were change in lumbar spine BMD (LSBMD) 6 months after ZOL and the proportion of patients who failed to maintain BMD. The study is ongoing (clinicaltrials.gov; NCT03087851). We included 61 participants and 59 patients completed follow-up 12 months after ZOL. Six months after ZOL, LSBMD had decreased significantly by (mean ± SE) 2.1% ± 0.9%, 4.3% ± 1.1%, and 3.0% ± 1.1% in the 6M, 9M, and OBS groups, respectively, and by 4.8% ± 0.7%, 4.1% ± 1.1%, and 4.7% ± 1.2% 12 months after ZOL in the 6M, 9M, and OBS groups, respectively (p