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A randomized, open-label, controlled trial of monthly oral minodronate or semiannual subcutaneous injection of denosumab for bone loss by androgen deprivation in Asian men with prostate cancer: the PRevention of Osteopenia with Minodronate And DEnosumab (PROMADE) study

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Abstract

Summary

There is still a lack of evidence that minodronate or denosumab prevents bone loss due to androgen deprivation therapy (ADT) in non-Western patients. This study showed that both drugs significantly improved lumbar spine and total hip bone mineral density in Asian men with prostate cancer who received ADT.

Introduction

To evaluate whether monthly oral minodronate or semiannual subcutaneous injection of denosumab improves bone mineral density (BMD) in Asian men with prostate cancer (PCa) receiving ADT.

Methods

A multicenter, open-label, randomized, controlled study including patients with hormone-sensitive PCa without bone metastasis receiving ADT was performed. Patients were randomized (1:1:1) to minodronate, denosumab, or no agent control groups. The primary end point was the mean percentage change in BMD at the lumbar spine at 12 months. Secondary end points were the mean percentage change in BMD at the femoral neck and total hip and changes in bone turnover markers. Statistical comparison was performed using analysis of covariance.

Results

Of the 147 subjects enrolled in this study, 102 were randomly assigned into the minodronate (n = 36), denosumab (n = 36), and control (n = 30) groups. The percentage change in BMD at the lumbar spine was significantly improved in the minodronate (2.5%, p < 0.05) and denosumab groups (4.0%, p < 0.01) compared with that in the control group (− 0.1%). Denosumab increased BMD at the femoral neck and total hip at 12 months, whereas minodronate only increased BMD at the total hip compared with controls (all p < 0.05). The percentage change in bone turnover markers at 12 months was significantly lower in the minodronate and denosumab groups compared with that in the control group (both p < 0.01).

Conclusion

Minodronate or denosumab can be used for preventing bone loss related to ADT in Asian patients with PCa.

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Abbreviations

ADT :

androgen deprivation therapy

AE :

adverse event

BMD :

bone mineral density

GnRH :

gonadotropin-releasing hormone

PCa :

prostate cancer

P1NP :

type I procollagen N-terminal propeptide

RANKL :

receptor activator of nuclear factor-kB ligand

SE :

standard error

SD :

standard deviation

TRACP-5b :

tartrate-resistant acid phosphatase-5b

YAM :

young adult mean

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Acknowledgments

We would like to thank all of Kansai Medical University members who supported this study, including Eriko Ozeki (medical assistant) and Yuya Koito, MD, at Kori Hospital, and Miki Sawa (medical department secretary), Yumi Oigo, MDS, and Ikuko Nakano, MDS, at Kansai Medical University Hospital. We thank Eric.

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Authors and Affiliations

  1. Department of Urology and Andrology, Kori Hospital, Kansai Medical University, 8-45 Kori Hondori cyo, Neyagawa, Osaka, 572-8551, Japan

    T. Yoshida

  2. Department of Urology and Andrology, Kansai Medical University Hospital, Hirakata, 2-3-1 Shin-machi, Hirakata, Osaka, 573-1191, Japan

    T. Yoshida, H. Kinoshita, H. Taniguchi, M. Yanishi, M. Sugi & T. Matsuda

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  1. T. Yoshida
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  2. H. Kinoshita
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  4. M. Yanishi
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  6. T. Matsuda
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Correspondence to T. Matsuda.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Yoshida, T., Kinoshita, H., Taniguchi, H. et al. A randomized, open-label, controlled trial of monthly oral minodronate or semiannual subcutaneous injection of denosumab for bone loss by androgen deprivation in Asian men with prostate cancer: the PRevention of Osteopenia with Minodronate And DEnosumab (PROMADE) study. Osteoporos Int 31, 1251–1259 (2020). https://doi.org/10.1007/s00198-019-05271-5

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