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Eldecalcitol is superior to alfacalcidol in maintaining bone mineral density in glucocorticoid-induced osteoporosis patients (e-GLORIA)

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Journal of Bone and Mineral Metabolism Aims and scope Submit manuscript

Abstract

Introduction

Eldecalcitol increases bone mineral density (BMD) and reduces vertebral fracture in patients with primary osteoporosis. However, the effect of eldecalcitol on BMD and fracture in glucocorticoid-induced osteoporosis (GIO) patients is unknown. This study was undertaken to compare the effect of eldecalcitol on BMD and fracture with that of alfacalcidol in GIO patients.

Materials and methods

A randomized, open-label, parallel group study was conducted to identify the effectiveness and safety of monotherapy with 0.75 μg eldecalcitol compared with 1.0 μg alfacalcidol in GIO patients.

Results

Lumbar spine BMD increased with eldecalcitol, but decreased with alfacalcidol at 12 and 24 months (between group difference 1.29%, p < 0.01, and 1.10%, p < 0.05, respectively). Total hip and femoral neck BMD were maintained until 24 months by eldecalcitol, but decreased by alfacalcidol (between group difference 0.97%, p < 0.05 and 1.22%, p < 0.05, respectively). Both bone formation and resorption markers were more strongly suppressed by eldecalcitol than by alfacalcidol. Eldecalcitol showed better effect on BMD than alfacalcidol in patients with no prevalent fracture and BMD > 70% of the young adult mean, and with ≤ 3 months of previous glucocorticoid treatment. No significant difference in the incidence of vertebral fracture was found, and the incidence of adverse events was similar between the two groups.

Conclusions

Eldecalcitol was more effective than alfacalcidol in maintaining BMD in GIO patients. Because eldecalcitol was effective in patients with no or short-term previous glucocorticoid treatment, as well as those without prevalent fracture or low BMD, eldecalcitol can be a good candidate for primary prevention of GIO.

Clinical trial registration number

UMIN000011700.

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Acknowledgements

This study was supported by a fund from Chugai Pharmaceutical Co. Ltd.

We thank all investigators and participating patients involved in this study at the following clinical sites in Japan: Asahi General Hospital, Chiba; Chibaken Saiseikai Narashino Hospital, Chiba; Fukuoka Tokushukai Hospital, Fukuoka; Fukuoka Yutaka Central Hospital, Fukuoka; Hiroshima Red Cross Hospital and Atomic-bomb Survivors Hospital, Hiroshima; Hyogo Prefectural Nishinomiya Hospital, Hyogo; Ishikawa Prefectural Central Hospital, Ishikawa; Itami City Hospital, Hyogo; Kagawa Prefectural Central Hospital, Kagawa; Kang Rheumatology Orthopedics Clinic, Kanagawa; Kansai Electric Power Hospital, Osaka; Kansai Medical University Hospital, Osaka; Kanzaki Municipal General Hospital, Himeji; Kashimoto Hospital, Osaka; Kawakita General Hospital, Tokyo; Kawasaki Municipal Hospital, Kanagawa; Keio University Hospital, Tokyo; Kindai University Nara Hospital, Nara; Kitasato University Medical Center, Saitama; Kobe City Medical Center West Hospital, Kobe; Kyushu Medical Center, Fukuoka; Kyushu University Beppu Hospital, Oita; Kyushu University Hospital, Fukuoka; Matsuyama Red Cross Hospital, Ehime; Mie Rheumatology Clinic, Mie; Minami-Akita Orthopedics Clinic, Akita; Minami-Okayama Medical Center, Okayama; Mitsui Memorial Hospital, Tokyo; Nagoya Rheumatology Clinic, Aichi; Nakama Municipal Hospital, Fukuoka; Nakamura Orthopedics Clinic, Kagoshima; Obase Hospital, Fukuoka; Okayama saiseikai General Hospital, Okayama; Osaka City University Hospital, Osaka; Osaka Kaisei Hospital, Osaka; Osaka-Minami Medical Center, Osaka; Osaki Citizen Hospital, Miyagi; Red Cross Nagasaki Genbaku Hospital, Nagasaki; Red Cross Okayama Hospital, Okayama; Rinku General Medical Center, Osaka; Sagawa Akira Rheumatology Clinic, Hokkaido; Saiseikai Suita Hospital, Osaka; Saitama Medical Center, Saitama; Saitama Medical University Hospital, Saitama; Shiminnomori Hospital, Miyazaki; Shimokitazawa Hospital, Tokyo; Shinko Hospital, Hyogo; Shinsuma Hospital, Osaka; Shirakawa Kosei General Hospital, Fukushima; Showa University Northern Yokohama Hospital, Kanagawa; Soshigaya Okura Clinic, Tokyo; St. Marianna University School of Medicine, Kanagawa; Tohoku University Hospital, Miyagi; Tokyo Metropolitan Ohtsuka hospital, Tokyo; Tomishiro Central Hospital, Okinawa; Tonan Hospital, Hokkaido; Tsurukami Clinic of Orthopedics and Rheumatology, Kumamoto;Utazu Hospital, Kagawa; Yokosuka Kyosai Hospital, Kanagawa;Yonezawa City Hospital, Yamagata; Yoshitama Rheumatology Internal Medicine Clinic, Kagoshima; Yu-Family Clinic, Miyagi

We thank the late Chikuma Hamada, Ph.D., Department of Business Engineering, Faculty of Engineering, Tokyo University of Science, for serving as statistical consultant. We also thank Mebix Inc., Tokyo, Japan, for supporting statistical analysis and data management, monitoring, auditing, and offering assistance for writing the manuscript, Musashi Image Joho Co., Ltd., Tokyo, Japan, for supporting fracture assessment, and LSI Medience Corporation, Tokyo, Japan, for measuring bone turnover markers.

Author information

Authors and Affiliations

  1. Fujii Memorial Institute of Medical Sciences, Tokushima University, Tokushima, 770-8530, Japan

    Toshio Matsumoto

  2. Laboratory for Autoimmune Diseases, RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa, Japan

    Kazuhiko Yamamoto

  3. Division of Rheumatology, Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan

    Tsutomu Takeuchi

  4. First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Fukuoka, Japan

    Yoshiya Tanaka

  5. Department of Orthopaedic Surgery, The University of Tokyo Graduate School of Medicine, Tokyo, Japan

    Sakae Tanaka

  6. Tamana Central Hospital, Tamana, Kumamoto, Japan

    Tetsuo Nakano

  7. The Open University of Japan, Nagasaki, Nagasaki, Japan

    Masako Ito

  8. Department of Radiology, Kawasaki Medical School, Kurashiki, Okayama, Japan

    Tatsushi Tomomitsu

  9. Department of Biostatistics and Bioinformatics, The University of Tokyo Graduate School of Medicine, Tokyo, Japan

    Akihiro Hirakawa

  10. Department of Orthopaedic Surgery and Rheumatology, Kindai University Nara Hospital, Ikoma, Nara, Japan

    Satoshi Soen

Authors
  1. Toshio Matsumoto
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  2. Kazuhiko Yamamoto
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  3. Tsutomu Takeuchi
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  4. Yoshiya Tanaka
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  5. Sakae Tanaka
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Contributions

TM, SS, KY, TT, YT, and ST planned the study design and performed the study. TN and MI analyzed the X-ray and adjudicated the vertebral fractures. TT analyzed the DXA and adjudicated BMD. AH planned and performed the statistical analysis. TM and SS interpreted the results. TM analyzed the results and wrote the initial draft. All authors contributed to discuss the results and approved the final manuscript.

Corresponding author

Correspondence to Toshio Matsumoto.

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Conflicts of interest

T.M. has received consulting fees from Chugai, Amgen Astellas Biopharma, Teijin Pharma, Daiichi-Sankyo and Asahi Kasei Pharma. K.Y. has received speaking fees, and/or honoraria from AbbVie, Astellas, AYUMI Pharma, Bristol-Myers Squibb, Chugai, Eisai, Janssen, Mitsubishi-Tanabe, Ono and UCB Japan. T.T. has received grants from Astellas, Chugai, Daiichi-Sankyo, Takeda, AbbVie, Asahi Kasei Pharma, Mitsubishi-Tanabe, Pfizer, Eisai, AYUMI Pharma, Nipponkayaku, Novartis and Shionogi. Honoraria from Astellas, AbbVie, AYUMI Pharma, Eisai., Gilead Sciences, GlaxoSmithKline, Sanofi., Taiho, Mitsubishi-Tanabe, Diaichi-Sankyo, Chugai, Taisho Pharma, Eli Lilly Japan, Novartis, Boehringer-Ingelheim, Nipponkayaku, Pfizer, Bristol–Myers Squibb, Janssen and UCB Japan. Y.T.　has received speaker fee and/or honoraria from Daiichi-Sankyo, Astellas, Chugai, Eli Lilly Japan, Pfizer, AbbVie, YL Biologics, Bristol-Myers Squibb, Takeda, Mitsubishi-Tanabe, Novartis, Eisai, Janssen, Teijin Pharma, and has received research grants from Asahi Kasei Pharma, Mitsubishi-Tanabe, Chugai, Takeda, Sanofi, Bristol-Myers Squibb, UCB Japan, Daiichi-Sankyo, Eisai and Ono. S.T. has received consulting fees, speaker fees, and/or honoraria from Amgen Astellas Biopharma, Astellas, Asahi Kasei Pharma, Chugai, Daiichi-Sankyo, Eisai, Eli Lilly Japan, Ono, Pfizer, Taisho Toyama Pharma and Teijin Pharma. M.I. has received consulting fees, speaker fees, honoraria, and/or research funding from Chugai, Astellas, Asahi Kasei Pharma, Daiichi-Sankyo, Eli Lilly Japan, MSD, Ono and Pfizer. A.H. has received consulting fees, speaker fees, honoraria, and/or research funding from Astellas, Ono and Teijin Pharma. S.S. has received consulting fees, speaker fees, and/or honoraria from Asahi Kasei Pharma, Astellas, Chugai, Daiichi-Sankyo, Eisai, Eli Lilly Japan, MSD, Ono, Pfizer, Takeda and Teijin Pharma. Other authors reported no conflict of interest related to this work.

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Matsumoto, T., Yamamoto, K., Takeuchi, T. et al. Eldecalcitol is superior to alfacalcidol in maintaining bone mineral density in glucocorticoid-induced osteoporosis patients (e-GLORIA). J Bone Miner Metab 38, 522–532 (2020). https://doi.org/10.1007/s00774-020-01091-4

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