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Real-World Effectiveness of Denosumab and Bisphosphonates on Risk of Vertebral Fractures in Women with Breast Cancer Undergoing Treatment with Aromatase Inhibitors

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Abstract

Bone-active drugs are recommended to protect the skeleton from detrimental actions of aromatase inhibitors (AIs). However, most of literature data are focused on bone mineral density (BMD), whereas data on fractures are scant. The aim of this prospective study was to investigate the real-life effectiveness of denosumab, oral bisphosphonates (BPs) and intravenous zoledronate on risk of vertebral fractures (VFs) induced by AIs. 567 consecutive women (median age 62 years, range 28–83) with early breast cancer undergoing treatment with AIs were evaluated for morphometric VFs and BMD at baseline and after 18–24 months of follow-up. After enrollment, 268 women (47.3%) started denosumab 60 mg subcutaneously every 6 months, 115 (20.3%) BPs (59 with oral BPs and, 56 with intravenous zoledronate 5 mg/12 months), whereas 184 women (32.5%) were not treated with bone-active drugs for several reasons. During follow-up, 54 women (9.5%) developed incident VFs in association with age of subjects (P < 0.001), baseline FRAX scores for major fractures (P < 0.001) and hip fractures (P = 0.003), pre-existing VFs (P < 0.001), change in BMD at lumbar spine (P = 0.015), femoral neck (P = 0.003) and total hip (P < 0.001). Risk of VFs was higher in subjects who were untreated as compared to those treated with bone-active drugs (32/184 vs. 22/383; P < 0.001). Specifically, fracture risk was significantly decreased by denosumab [odds ratio (OR) 0.22; P < 0.001] and zoledronate (OR 0.27; P = 0.035), but not by oral BPs (P = 0.317). These data suggest that in real-world clinical practice, denosumab and zoledronate can reduce AI-related risk of VFs after only 24 months of treatment.

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Data Availability

The datasets generated and analyzed during the current study are available in the ZENODO repository.

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Funding

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

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Author notes

  1. Gherardo Mazziotti and Rebecca Pedersini have equally contributed to this work.

Authors and Affiliations

  1. Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini, 4, 20090, Pieve Emanuele, MI, Italy

    Gherardo Mazziotti, Flaminia Carrone, Alberto Zambelli & Andrea G. Lania

  2. Endocrinology, Diabetology and Andrology Unit, IRCCS Humanitas Research Hospital, Rozzano, MI, Italy

    Gherardo Mazziotti, Walter Vena, Flaminia Carrone, Stella Pigni & Andrea G. Lania

  3. Medical Oncology Unit, ASST Spedali Civili Di Brescia, Brescia, Italy

    Rebecca Pedersini, Walter Vena, Deborah Cosentini, Edda L. Simoncini & Alfredo Berruti

  4. Cancer Center IRCCS Humanitas Research Hospital, Rozzano, MI, Italy

    Rosalba Torrisi & Alberto Zambelli

  5. Radiology Unit, ASST Spedali Civili Di Brescia, Brescia, Italy

    Davide Farina

  6. Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, Brescia, Italy

    Davide Farina & Alfredo Berruti

  7. Department of Radiology, IRCCS Humanitas Research Hospital, Rozzano, MI, Italy

    Luca Balzarini

  8. Endocrinology and Diabetology Center, Humanitas Gavazzeni-Castelli, Bergamo, Italy

    Walter Vena

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Contributions

GM and AGL had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. GM, WV, RP, AGL, AB: Concept and design. GM, WV, RP, DC, FC, SP, RT, ELS, AZ: Enrollment of patients. LB, DF, WV, GM: Radiological examinations. GM, WV, RP, AGL, AB: Acquisition, analysis or interpretation of data. RP, GM: Statistical analysis. GM, AB, AGL: Drafting the manuscript. GM, WV, RP, AZ, AGL, AB: Critical revision of the manuscript for important intellectual content.

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Correspondence to Andrea G. Lania.

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Conflict of interest

The Authors declare no competing non-financial interests but the following competing financial interests: Dr. Mazziotti received consultancy fees from Novartis, Ipsen, Eli Lilly and lecture fees from Amgen and Abiogen, outside the submitted work; Dr. Vena received grants from IBSA Pharmaceutical outside the submitted work; Dr. Torrisi received research grants from Pfizer, consultancy fees from MSD and lecture fees from Pfizer, Eli Lilly, EISAI and Genomic Health outside the submitted work; Dr. Zambelli received consultancy fees from Roche, Novartis, Pfizer, Eli Lilly & Co., AstraZeneca, Genomic Health; Dr. Lania received grants from Pfizer and consultancy fees from Ipsen, outside the submitted work; Dr. Berruti reports receiving grants and personal fees from Janssen Cilag, grants and personal fees from Astellas, and personal fees from Bayer outside the submitted work.

Human and animal rights and informed consent

All the procedures performed in the study were in accordance with the ethical standards of the Ethics Committees of IRCCS Humanitas Research Hospital, Rozzano-Milan, Italy, Spedali Civili Hspital of Brescia, Italy and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. All the enrolled subjects gave their informed consent to use the clinical and biochemical data for research purposes.

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223_2022_1011_MOESM2_ESM.tif

Supplementary file2 (TIF 113 KB) Supplementary Figure 1 Flow-chart of enrollment of 567 women with early breast cancer starting aromatase inhibitor (AI) therapy and then stratified to be treated or not with bone-active drugs

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Mazziotti, G., Pedersini, R., Vena, W. et al. Real-World Effectiveness of Denosumab and Bisphosphonates on Risk of Vertebral Fractures in Women with Breast Cancer Undergoing Treatment with Aromatase Inhibitors. Calcif Tissue Int 111, 466–474 (2022). https://doi.org/10.1007/s00223-022-01011-w

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