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Effects of denosumab on bone mineral density in Japanese women with osteoporosis treated with aromatase inhibitors for breast cancer

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Abstract

Adjuvant aromatase inhibitor (AI) therapy, for hormone receptor-positive breast cancer, in postmenopausal women is associated with bone loss, leading to an increased risk of fractures. Denosumab, an antibody raised against the receptor activator of nuclear factor-κB ligand, has been proven to protect against AI-induced bone loss. Hence, we aimed to determine whether denosumab is effective in postmenopausal Japanese women with osteoporosis, treated with AI. We prospectively evaluated the bone mineral density (BMD) in the lumbar spine and the bilateral femoral neck in 102 postmenopausal women with clinical hormone receptor-positive breast cancer, stages I–IIIA, during a postoperative period of 12 months. The other inclusion criteria for this study were: women that should receive AIs as adjuvant therapy and those with evidence of osteoporosis (lumbar spine or bilateral femoral neck BMD, equivalent to T-score classification of ≤ − 2.5) upon enrollment. The patients received supplemental calcium, vitamin D, and 60 mg of subcutaneous denosumab every 6 months. The BMD of the lumber spine increased by 4.9 and 6.6% at 6 and 12 months, respectively. An increase in BMD was observed at the femoral neck, bilaterally. Hypocalcemia ≥ grade 2, osteonecrosis of the jaw, and non-traumatic clinical fracture were not observed in this study. Our findings revealed that biannual treatment with denosumab is associated with a great increase of BMD in Japanese women receiving adjuvant AI therapy, irrespective of their previous history of AI therapy.

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Abbreviations

AI:

Aromatase inhibitor

BMD:

Bone mineral density

DXA:

Dual-energy X-ray absorptiometry

ONJ:

Osteonecrosis of the jaw

RANKL:

Receptor activator of nuclear factor κ-B ligand

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Acknowledgements

We thank all the participating investigators, Hiroshi Koyama; Nara City Hospital, Takayuki Matsuda; Saiseikai Kyoto Hospital, Makoto Kato; Kato Breast Surgery Clinic. No funding was received for this study.

Author information

Authors and Affiliations

  1. Department of Endocrine and Breast Surgery, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachi-hirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan

    Katsuhiko Nakatsukasa, Yoshimi Ouchi, Kouichi Sakaguchi, Yoshifumi Fujita & Tetsuya Taguchi

  2. Nara City Hospital, Nara, Japan

    Hiroshi Koyama

  3. Saiseikai Kyoto Hospital, Kyoto, Japan

    Takayuki Matsuda

  4. Kato Breast Surgery Clinic, Shiga, Japan

    Makoto Kato

  5. Department of Surgical Pathology, Kyoto Prefectural University of Medicine, Kyoto, Japan

    Eiichi Konishi

Authors
  1. Katsuhiko Nakatsukasa
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  2. Hiroshi Koyama
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  3. Yoshimi Ouchi
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  4. Kouichi Sakaguchi
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  5. Yoshifumi Fujita
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  6. Takayuki Matsuda
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  7. Makoto Kato
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  8. Eiichi Konishi
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  9. Tetsuya Taguchi
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Corresponding author

Correspondence to Tetsuya Taguchi.

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Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

The study was approved by the Institutional Review Board of Kyoto Prefectural University of Medicine, on January 10, 2014, and the conducted in accordance with the Helsinki Declaration of 1975, as revised in 1983. This study was registered with the UMIN Clinical Trial Registry (UMIN-CTR, UMIN000027425). Informed consent was obtained from all individual participants included in the study.

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Nakatsukasa, K., Koyama, H., Ouchi, Y. et al. Effects of denosumab on bone mineral density in Japanese women with osteoporosis treated with aromatase inhibitors for breast cancer. J Bone Miner Metab 37, 301–306 (2019). https://doi.org/10.1007/s00774-018-0917-0

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  • DOI: https://doi.org/10.1007/s00774-018-0917-0

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