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

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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.

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Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

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Authors and Affiliations

  1. Center of Bone Diseases, Service of Rheumatology, CHUV, Lausanne University Hospital and University of Lausanne, Rue Pierre-Decker 4, 1011, Lausanne, Switzerland

    Elena Gonzalez-Rodriguez, Bérengère Aubry-Rozier, Delphine Stoll & Olivier Lamy

  2. Service of Endocrinology, Diabetes and Metabolism, CHUV, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland

    Elena Gonzalez-Rodriguez

  3. Breast Center, CHUV, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland

    Khalil Zaman

  4. Service of Internal Medicine, CHUV, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland

    Olivier Lamy

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  1. Elena Gonzalez-Rodriguez
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  2. Bérengère Aubry-Rozier
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  3. Delphine Stoll
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  4. Khalil Zaman
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  5. Olivier Lamy
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Correspondence to Elena Gonzalez-Rodriguez.

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EGR, BAR, DS, KZ, and OL declare that they have no conflict of interest.

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Studies were in accordance with the ethical standards of the institutional research committee (CER-VD 2017-02135) and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Informed consent was obtained from all individual participants included in the study.

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Gonzalez-Rodriguez, E., Aubry-Rozier, B., Stoll, D. et al. Sixty spontaneous vertebral fractures after denosumab discontinuation in 15 women with early-stage breast cancer under aromatase inhibitors. Breast Cancer Res Treat 179, 153–159 (2020). https://doi.org/10.1007/s10549-019-05458-8

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  • DOI: https://doi.org/10.1007/s10549-019-05458-8

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