Endocrine Abstracts

Objective

Several studies showed that patients discontinuing denosumab (Dmab) may experience bone loss and incident vertebral fractures (VFx) due to a rebound bone turnover increase, suggesting the need of anti-resorptive (i.e. bisphosphonate BPs) therapy to mitigate this occurrence. However, the morphometric VFx (morphoVFx) incidence after Dmab discontinuation is unknown and scarce data are available about the BPs effect on BMD changes and Fx risk in this setting.

Methods

In this monocentric retrospective study, 120 patients (111 females) discontinuing Dmab (mean injections n. 6.2 ± 2.7) were included. After Dmab discontinuation, 19 patients have not been treated with BPs (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, 73 zoledronate single infusion). We evaluated the BMD variation (∆) and the incidence of both clinical VFx and morphoVFx in Treated Group and Non-treated Group.

Results

After Dmab discontinuation the mean ∆BMD at lumbar spine (LS), femoral neck (FN) and total hip (TH) were not different between the Treated Group (-2.7 ± 6.5%, -3.0 ± 7.3% and 2.3 ± 0.8%, respectively) and Not-Treated Group (-0.8 ± 5.8%, -5.1 ± 6.7% and -0.2 ± 7.7%, respectively, P = ns for all comparisons). The number of patients with BMD at TH lower than prior to Dmab administration was lower in Treated Group (8.9%) than in Not Treated Group (35.7%, P = 0.046), while no differences were found between the two groups at LS (12.9% and 26.3%, respectively) and FN (17.8% and 21.1%, respectively, P = ns for all comparisons). Patients in Treated Group had a lower VFx incidence (n = 6, 5.9%, 3 clinical, 3 morphoVFx) than patients in Not-treated Group (n = 4, 21.1%, 4 clinical, 3 multiple), respectively, in spite of a comparable fracture risk profile at the time of Dmab initiation. The VFx incidence was independently associated with the lack of BPs treatment (odds ratio 16.7, 95% confidence interval 1.8–142.8, P = 0.013) but not with number of Dmab injections, age, discontinuation of BPs administration at least 12 months before Dmab initiation, BMD at Dmab withdrawal and multiple VFx prevalence at Dmab initiation.

Conclusions

The Dmab withdrawal is associated with an increased risk of clinical VFx. The treatment with oral BPs or with a single zoledronate infusion reduces but not abolishes the increased VFx risk after Dmab withdrawal.