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The duration of denosumab treatment and the efficacy of zoledronate to preserve bone mineral density after its discontinuation

Polyzois Makras 1Natasha M Appelman-Dijkstra 2Socrates E Papapoulos 2Sandra van Wissen 1Elizabeth M Winter 2Stergios A Polyzos 3Maria P Yavropoulou 1 4Athanasios D Anastasilakis 5

J Clin Endocrinol Metab doi: 10.1210/clinem/dgab321. 


Context: Zoledronate is used to prevent bone loss following denosumab discontinuation but its efficacy differs among studies.

Objective: To test if the duration of denosumab treatment affects the efficacy of subsequent zoledronate infusion.

Design: Multicenter, prospective cohort study.

Setting: Two Greek and one Dutch bone centers.

Patients: Postmenopausal women (n=47) who received a single zoledronate infusion 6 months after the last denosumab injection and were followed for 1 year. Twenty-seven women received ≤ 6 denosumab injections (≤ 6 Group) and twenty received > 6 denosumab injections (> 6 Group).

Main outcome measure: Changes in lumbar spine (LS) BMD.

Results: At 12 months LS- BMD values were maintained in the ≤6 Group (0.98±0.10 to 0.99±0.9/ g/cm 2 p=0.409) but decreased significantly in the >6 Group (1.0 ± 0.11 to 0.93 ± 0.12 g/cm 2, p <0.001). The percent change of LS-BMD of the ≤ 6 Group (+1.0%) was significantly different (p<0.001) from the change of the > 6 Group (-7.0%). In the whole cohort the duration of denosumab treatment was negatively correlated with the percentage change of LS-BMD (rs:-0.669, p<0.001) but not with the change of FN-BMD. Bone turnover markers increased in all patients 6 months following zoledronate administration with no difference between the two groups.

Conclusions: The duration of denosumab treatment significantly affects the efficacy of subsequent zoledronate infusion to maintain BMD gains. Frequent follow-up of patients treated with denosumab longer than 3 years is advisable as additional therapeutic interventions may be needed.