Bisphosphonates after Denosumab withdrawal reduce the vertebral fractures incidence

Objective: Several studies showed the occurrence of vertebral fracture (VFx) in patients discontinuing denosumab (Dmab), suggesting the need of bisphosphonate (BPs) therapy to mitigate this VFx risk increase. However, the morphometric VFx (morphoVFx) incidence after Dmab discontinuation and the BPs effect on VFx risk in this setting are still a matter of debate.Design: Retrospective, monocentric study.Methods:In 120 patients (111 females) discontinuing Dmab, 19 have not been treated (Not-treated Group, 16 females, age 63.5±15.0 years) and 101 patients have been treated (Treated Group, 95 females, age 70.0±10.6 years) with BPs (28 alendronate, ALN; 73 zoledronate, ZOL, single infusion), respectively. We evaluated the incidence of both clinical VFx and morphoVFx in Treated Group and Non-treated Group.Results: Patients in Treated Group showed a 5.5% VFx incidence (n=6, 3 clinical, 3 morpho VFx), which was anyway lower than Not-treated Group patients (n=4, 21.1%, 4 clinical, 3 multiple, p=0.029), despite a comparable FRAX score at the time of Dmab initiation. The logistic regression analysis showed that the VFx incidence was independently associated with the lack of BPs treatment (odds ratio 13.9, 95% confidence interval 1.7-111.1, p=0.014), but not with the number of Dmab injections, age, duration of BPs before Dmab initiation, the BMD at Dmab withdrawal and the prevalence of VFx at Dmab withdrawal.Conclusions: The Dmab withdrawal is associated with an increased risk of clinical but not morphometric VFx. Therapy with ALN or with a single ZOL treatment are partially effective in reducing the increased VFx risk after Dmab withdrawal.