The Duration of Denosumab Treatment and the Efficacy of Zoledronate to Preserve Bone Mineral Density After Its Discontinuation

Makras, P.; Appelman-Dijkstra, N.M.; Papapoulos, S.E.; Wissen, S. van; Winter, E.M.; Polyzos, S.A.; Yavropoulou, M.P.; Anastasilakis, A.D.

doi: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.Methods: This multicenter, prospective cohort study, conducted at 2 Greek and 1 Dutch bone centers, included 47 postmenopausal women (n=47) who received a single zoledronate infusion 6 months after the last denosumab injection and then were followed for 1 year. Twenty-seven women received <= 6 denosumab injections (<= 6 Group) and 20 received>6 denosumab injections (> 6 Group). The main outcome measure was changes in lumbar spine (LS) bone mineral density (BMD).Results: At 12 months LS-BMD values were maintained in the <= 6 Group (0.980.10 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...Show moreContext: 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.Methods: This multicenter, prospective cohort study, conducted at 2 Greek and 1 Dutch bone centers, included 47 postmenopausal women (n=47) who received a single zoledronate infusion 6 months after the last denosumab injection and then were followed for 1 year. Twenty-seven women received <= 6 denosumab injections (<= 6 Group) and 20 received>6 denosumab injections (> 6 Group). The main outcome measure was changes in lumbar spine (LS) bone mineral density (BMD).Results: At 12 months LS-BMD values were maintained in the <= 6 Group (0.980.10 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 (r(s) = -0.669, P<0.001) but not with the change of femoral neck (FN)-BMD. Bone turnover markers increased in all patients 6 months following zoledronate administration with no difference between the 2 groups.Conclusion: 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.Show less

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The Duration of Denosumab Treatment and the Efficacy of Zoledronate to Preserve Bone Mineral Density After Its Discontinuation