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

Abstract 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 (0.98 ± 0.10 to 0.99 ± 0.9 g/cm2, P = 0.409) but decreased significantly in the > 6 Group (1.0 ± 0.11 to 0.93 ± 0.12 g/cm2, 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 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.