Endocrine Abstracts

Introduction: Denosumab discontinuation rapidly reverses bone turnover inhibition and eliminates anti-fracture protection. Multiple vertebral fractures (MVF) were reported in this scenario. Previously, we reported a retrospective real-life analysis designed to estimate fracture risk following denosumab discontinuation. Here we report a patient-level data of a subgroup with MVF.

Methods: Via computerized database of Maccabi Healthcare Services, persistent denosumab users (PU) and denosumab discontinuers (DD) were detected. MVF were adjudicated by an expert’s chart review. Patients’ baseline characteristics, osteoporosis therapy, variables related to denosumab treatment and discontinuation, and post-MVF treatments were retrieved.

Results: In the core study, 12 female patients with MVF were identified among 1500 DD (MVF-DD) and 2 among 1610 PU (MVF-PU), P < 0.01. The MVF patients were comparable in age (71 ± 12 vs 68 ± 11), BMI (26.4 ± 2.9 vs 22.6 ± 2) and eGFR (73 ± 27 vs100 ± 7.7) among DD and PU, respectively. Osteoporotic fractures prior to denosumab treatment were prevalent in 41.6% MVF-DD and 100% MVF-PU (P = 0.4615). Femoral neck T-scores were -2.7 ±1 vs -3.5 ± 0.56 (P = 0.33) in the MVF-DD and MVF-PU, respectively. 75% of MVF-DD versus 100% of MVF-PU received osteoporosis medications prior to denosumab. MVF occurred 134 ± 76 days post DD and 57 ± 35 days from the last dose in PU. Two patients in the MVF-DD passed away. One patient suffered from additional VF. Denosumab, teriparatide, oral and IV bisphosphonates were prescribed in various sequences post-MVF and two patients underwent vertebroplasty/kyphoplasty.

Conclusions: MVF occurred in high-risk individuals in both groups. There is no consistency in post-denosumab discontinuation management and studies are urgently needed to reveal the safest approach. Denosumab discontinuation should be avoided, especially in patients with high-risk profile.