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

Breast Cancer Res Treat. 2020 Jan;179(1):153-159. doi: 10.1007/s10549-019-05458-8. Epub 2019 Oct 9.

Abstract

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.

Keywords: Aromatase inhibitors; Breast cancer; Denosumab discontinuation; Rebound effect; Spontaneous multiple vertebral fractures.

MeSH terms

  • Absorptiometry, Photon
  • Aged
  • Aromatase Inhibitors / adverse effects
  • Aromatase Inhibitors / therapeutic use*
  • Bone Density Conservation Agents / administration & dosage*
  • Bone Density Conservation Agents / adverse effects
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / pathology
  • Denosumab / administration & dosage*
  • Denosumab / adverse effects
  • Diphosphonates / therapeutic use
  • Female
  • Fractures, Bone / chemically induced
  • Fractures, Bone / epidemiology*
  • Humans
  • Middle Aged
  • Neoplasm Staging
  • Retrospective Studies
  • Treatment Outcome

Substances

  • Aromatase Inhibitors
  • Bone Density Conservation Agents
  • Diphosphonates
  • Denosumab