J Bone Miner Res doi: 10.1002/jbmr.4098.
Discontinuing denosumab is associated with bone loss and possibly increased fracture risk. We investigated if treatment with zoledronate could prevent bone loss and if the timing of the zoledronate infusion influenced the outcome. 2-year randomized, open label, interventional study including 61 patients with osteopenia, discontinuing denosumab after 4.6 ± 1.6 years. We administrated zoledronate six (6 M group, n = 20) or nine months (9 M 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) six months after zoledronate 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 zoledronate. Six months after zoledronate, LSBMD had decreased significantly by 2.1 ± 0.9% (mean ± SEM), 4.3 ± 1.1% and 3.0 ± 1.1% in the 6 M, 9 M and OBS groups, respectively and by 4.8 ± 0.7%, 4.1 ± 1.1%, and 4.7 ± 1.2% 12 months after zoledronate in the 6 M, 9 M and OBS groups, respectively (p < 0.02, no between group differences). BMD loss above the least significant change was seen in all groups; at the spine: 6 M: n = 6 (30%), 9 M: n = 9 (45%), OBS: n = 9 (47%); and at the total hip: 6 M: n = 1 (5%), 9 M: n = 5 (25%), OBS: n = 2 (11%). In the 6 M group p-cross-linked C-terminal telopeptide (p-CTX) decreased initially, but increased rapidly thereafter, and six months after ZOL, p-CTX was 0.60 ± 0.08 g/L. p-CTX increased rapidly in the 9 M and OBS groups, was suppressed by ZOL but increased again thereafter; p-CTX was 0.47 ± 0.05 μg/L and 0.47 ± 0.05 μg/L six months after zoledronate, respectively. Incident vertebral fractures were seen in two women in the 9 M group. Treatment with zoledronate irrespective of the timing did not fully prevent loss of BMD in patients discontinuing denosumab