Sixty spontaneous vertebral fractures after denosumab discontinuation in 15 women with early-stage breast cancer under aromatase inhibitors.

PURPOSE: At denosumab discontinuation, bone turnover markers increase and the gained BMD is lost. In postmenopausal osteoporosis, there is an increased risk of spontaneous vertebral fractures (VFs) of about 1 to 10%, rarely described in women under denosumab for aromatase inhibitors (AI)-treated breast cancer. We aim to describe the characteristics of 15 patients under denosumab given for AI-treated early-stage breast cancer that presented VFs at its discontinuation. METHODS: Single-center retrospective case series of 15 patients. We report clinical data, dual X-ray absorptiometry values at denosumab initiation and discontinuation, and serum B-crosslaps dosage at the time of VF occurrence (before denosumab resumption). RESULTS: Fifteen women (66.4 ± 7.1 years at denosumab discontinuation) that received AI for 5.0 ± 0.6 years, denosumab 60 mg for 8.2 ± 2.0 doses, and developed 60 VFs at denosumab discontinuation, were followed for 24.4 ± 9.5 months. Patients suffered from 1 to 11 (mean 4.0 ± 1.9) clinical VFs within 7 to 16 months after last denosumab injection. VFs developed earlier in patients with longer denosumab treatment (R2 = 0.29, p = 0.04) and in patients without osteoporosis before denosumab (9.4 ± 2.0 vs. 13.0 ± 2.0 months; p = 0.005). Serum B-crosslaps at the time of VFs tended to be higher in patients with earlier VFs (R2 = 0.47; p = 0.06) or with longer denosumab treatment (R2 = 0.48; p = 0.06). Denosumab was resumed in all patients, then switched for a bisphosphonate in eight. No new VFs occurred during follow-up. CONCLUSIONS: Despite an apparently low fracture risk, women under denosumab for AI-treated early-stage breast cancer develop spontaneous VFs at denosumab discontinuation. This risk increases with treatment duration and may be prevented by a potent bisphosphonate.

Stopping Denosumab.

PURPOSE OF REVIEW: Denosumab discontinuation is associated with a rebound effect manifesting by an increased risk of multiple spontaneous vertebral fractures. The purpose of this review is to (1) better characterize this risk and (2) find solutions to avoid it. RECENT FINDINGS: In the absence of a potent bisphosphonate prescription at denosumab discontinuation, the frequency of multiple vertebral fractures is common or frequent (≥ 1/100 and < 1/10). In five recent case series, the median number of vertebral fractures was 5 within 7 to 20 months (median 11) after the last denosumab injection. Prescribing bisphosphonate before starting denosumab and/or after stopping denosumab may reduce this risk. However, only small case series have evaluated these strategies. After the second denosumab dose, there is a rebound effect with an increased risk of multiple vertebral fractures. A potent bisphosphonate prescribed at denosumab discontinuation could reduce this risk. As denosumab discontinuation is characterized by many uncertainties, denosumab is a second-line treatment for osteoporosis. Studies are urgently needed to define the management of denosumab discontinuation.