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Long-term safety and effectiveness of denosumab in Japanese patients with osteoporosis: 3-year post-marketing surveillance study

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Journal of Bone and Mineral Metabolism Aims and scope Submit manuscript

Abstract

Introduction

Denosumab is a humanized IgG2 monoclonal antibody that was approved for the treatment of osteoporosis in Japan in 2013. This study aimed to investigate the long-term safety and effectiveness of denosumab in Japanese patients with osteoporosis in daily clinical practice.

Materials and methods

This 3-year, prospective, observational, post-marketing study included patients who initiated treatment with denosumab (60 mg/6 months) for osteoporosis. Data were assessed at baseline, 3, 6, 12, 24 and 36 months. Key endpoints were adverse events (AEs), adverse drug reactions (ADRs), occurrence of osteoporotic fractures, bone mineral density (BMD), and bone turnover markers. Multivariate analyses were conducted to identify predictors of hypocalcaemia and percent change in BMD.

Results

Overall, 3534 patients were assessed (mean 75.7 years; 89.8% women). In total, 298 patients (8.4%) developed ADRs; the most common was hypocalcaemia (3.9%). Hypocalcaemia risk was significantly increased in patients with creatinine clearance < 30 mL/min, no prior use of bisphosphonates, prior use of calcium and vitamin D preparations, baseline serum calcium < 8.5 mg/dL, and no concomitant use of calcium or vitamin D preparations. Six patients had adjudicated osteonecrosis of the jaw. Lumbar spine BMD increased significantly from baseline (mean percent change: 11.4% at 36 months). All bone turnover markers decreased significantly from baseline. Over 3 years, 3.3% of patients developed a new osteoporotic fracture.

Conclusions

This study confirmed the long-term safety and effectiveness of denosumab in Japanese patients with osteoporosis in daily clinical practice. No new safety signals were identified.

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Acknowledgements

We are deeply grateful to the investigators and participants of the survey. This study was sponsored by Daiichi Sankyo Co., Ltd. (Tokyo, Japan). In addition, the authors would like to thank Go Kuratomi, PhD, and Catherine Rees, of Springer Healthcare Communications, who wrote the outline and the subsequent drafts of this manuscript, respectively, and Sarah Greig, PhD, of Springer Healthcare Communications who assisted with manuscript revisions post-submission. This medical writing assistance was funded by Daiichi Sankyo Co., Ltd. This study was sponsored by Daiichi Sankyo Co., Ltd. (Tokyo, Japan).

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Authors and Affiliations

  1. Department of Orthopaedic Surgery, Graduate School of Medicine, The University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan

    Sakae Tanaka

  2. Post Marketing Study Department, Daiichi Sankyo Co., Ltd., 3-5-1, Nihonbashi Honcho, Chuo-ku, Tokyo, 103-8426, Japan

    Hideki Mizutani, Eri Tsuruya, Ryoko Fukuda & Kiyoka Kuge

  3. Biostatistics and Data Management Department, Daiichi Sankyo Co., Ltd., Tokyo, Japan

    Naoki Okubo

Authors
  1. Sakae Tanaka
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  2. Hideki Mizutani
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  3. Eri Tsuruya
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  4. Ryoko Fukuda
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  5. Kiyoka Kuge
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  6. Naoki Okubo
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Corresponding author

Correspondence to Hideki Mizutani.

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Conflict of interest

S. Tanaka received consulting fees, speaking fees and/or honoraria from Daiichi Sankyo Co., Ltd. H. Mizutani, E. Tsuruya, R. Fukuda, K. Kuge and N. Okubo are employees of Daiichi Sankyo Co., Ltd.

Ethical approval

This study was conducted in accordance with the Japanese GPSP guidelines. Under these guidelines, the requirement for written informed consent is waived because treatment is in accordance with clinical practice.

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Tanaka, S., Mizutani, H., Tsuruya, E. et al. Long-term safety and effectiveness of denosumab in Japanese patients with osteoporosis: 3-year post-marketing surveillance study. J Bone Miner Metab 39, 463–473 (2021). https://doi.org/10.1007/s00774-020-01180-4

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  • DOI: https://doi.org/10.1007/s00774-020-01180-4

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