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Morphometric vertebral fractures in patients with castration-resistant prostate cancer undergoing treatment with radium-223: a longitudinal study in the real-life clinical practice

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Abstract

Purpose

Radium-223 was associated with high incidence of non-vertebral fractures in patients with castration-resistant prostate cancer (CRPC). However, it is still unclear whether radium-223 may induce skeletal fragility regardless of other therapies for CRPC. We aimed at evaluating the prevalence, incidence, and determinants of vertebral fractures (VFs), i.e., the most frequent complication of skeletal fragility, in CRCP patients undergoing radium-223 therapy in the real-life clinical practice.

Methods

We retrospectively reviewed 49 CRPC patients with symptomatic bone metastases treated with radium-223. Patients received median number of four radium-223 doses (range: 2–6) and were followed-up for a median period of 11 months (range: 6–44). VFs were assessed by a quantitative morphometry using lateral images of spine 11C-Choline PET/CT, excluding from the analysis the vertebral bodies affected by bone metastases.

Results

Before radium-223 administration, 24 patients (49%) had VFs significantly associated with duration of androgen deprivation therapy (ADT; odds ratio 1.29) and previous abiraterone therapy (odds ratio 3.80). During radium-223 therapy, incident VFs occurred in 25% of patients, in relationship with prevalent VFs (hazard ratio 6.89) and change in serum total alkaline phosphatase values (hazard ratio 0.97), whereas the correlations with ADT and abiraterone therapy were lost. Noteworthy, the risk of VFs did not correlate with the therapeutic end points of radium-223.

Conclusions

This study provides a first evidence that in real-life clinical practice, radium-223 therapy may induce skeletal fragility with high risk of VFs, likely by inhibition of bone formation and independently of ADT and abiraterone therapy.

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Data availability

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

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  1. These authors contributed equally: Gherardo Mazziotti, Marcello Rodari

Authors and Affiliations

  1. Endocrinology, Diabetology and Andrology Unit, Metabolic Bone Diseases and Osteoporosis Section, Humanitas Clinical and Research Center, IRCCS, Milan, Italy

    Gherardo Mazziotti

  2. Department of Biomedical Sciences, Humanitas University, Milan, Italy

    Gherardo Mazziotti & Arturo Chiti

  3. Unit of Nuclear Medicine, Humanitas Clinical and Research Center, IRCCS, Milan, Italy

    Marcello Rodari, Fabrizia Gelardi, Giovanni Tosi, Giovanna Pepe & Arturo Chiti

  4. Department of Oncology, Humanitas Clinical and Research Center, IRCCS, Milan, Italy

    Paolo A. Zucali

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Contributions

M.R. and G.M. planned the study analyzed data and drafted the manuscript; G.P. analyzed data and reviewed images; F.G. performed article search and selection. A.C. conceptualized the study, coordinated the study workflow, critically reviewed the manuscript. All the authors reviewed the final version of the text.

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Correspondence to Gherardo Mazziotti.

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Conflict of interest

G.M. was consultant for Ipsen and Eli Lilly. A.C. received speaker honoraria from General Electric and Sirtex Medical System, acted as scientific advisor to Blue Earth Diagnostics and Advanced Accelerator Applications, and benefited from an unconditional grant from Sanofi to Humanitas University. All honoraria are outside the scope of the submitted work. All other authors declare no competing interests.

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Mazziotti, G., Rodari, M., Gelardi, F. et al. Morphometric vertebral fractures in patients with castration-resistant prostate cancer undergoing treatment with radium-223: a longitudinal study in the real-life clinical practice. Endocrine 69, 204–211 (2020). https://doi.org/10.1007/s12020-020-02277-6

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