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Minodronate combined with alfacalcidol versus alfacalcidol alone for glucocorticoid-induced osteoporosis: a multicenter, randomized, comparative study

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Abstract

Introduction

This study compared the clinical usefulness of minodronate (50 mg/4 weeks) plus alfacalcidol (1 μg/day) (Group M) with that of alfacalcidol alone (1 μg/day) (Group A) for treating glucocorticoid-induced osteoporosis.

Materials and methods

The primary endpoints were the changes from baseline in lumbar spine (LS) bone mineral density (BMD) and the cumulative incidence of vertebral fracture at 24 months; secondary endpoints included the changes from baseline in total hip (TH) BMD and bone turnover markers.

Results

Of 164 patients enrolled, 152 (Group M, n = 75; Group A, n = 77) were included in the analysis of efficacy. At each time point and at 24 months, LS BMD and TH BMD were significantly higher in Group M than in Group A. The 152 patients were divided into two subgroups that were previously treated with glucocorticoids for ≤ 3 months or > 3 months. In both subgroups, the changes from baseline in LS BMD and TH BMD from baseline at 24 months had increased more in Group M than in Group A. There were no differences found in the incidence of vertebral fracture between the groups, because the number of enrolled patients was lesser than that initially expected. In Group M, both bone formation and resorption markers significantly decreased from baseline at 3 months and maintained at 6, 12, and 24 months.

Conclusions

Minodronate plus alfacalcidol was more effective than alfacalcidol alone in increasing BMD and was effective in increasing BMD for both prevention and treatment. Therefore, minodronate can be a good candidate drug for the treatment of glucocorticoid-induced osteoporosis.

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Acknowledgement

We thank all investigators and participating patients involved in this study at the following clinical sites in Japan: Yokohama Rosai Hospital, Murayama Medical Center,Katayama Seikeigeka Rheumatism Clinic, Toyota Kosei Hospital, Kouseiren Namerikawa Hospital, Suzuki-clinic, Clinic of a wind, Komazawa, Saitama Medical Center, Juntendo University Shizuoka Hospital, Kanazawa Medical University Himi Municipal Hospital, JCHO Chukyo Hospital, Japanese Red Cross Medical Center, Shirasawa Orthopedic Clinic, Saito Clinic, Takikawa Municipal Hospital, NHO Asahikawa Medical Center, Soshigaya Okura Clinic, Hokkaido Medical Center for Rheumatic Diseases, Kawasaki Municipal Hospital, Tohno Chuo Clinic, Tokyo Dental College Ichikawa General Hospital, Tokushima University Hospital, Kindai University Nara Hospital, Sagawa Akira Rheumatology Clinic, Utazu Hoapital, Saiseikai Kanazawa Hospital, Sasebo Chuo Hospital, Tomishiro Central Hospital, NHO Kure Medical Center and Chugoku Cancer Center, Matsuyama Red Cross Hospital, Matsubara Rheumatology and Orthopedics Clinic, Kansai Medical University Hospital, MAYFLOWER Hospital, Shiminnomori Hospital, Kumamoto Kinoh Hospital, Tsurukami Clinic of Orthopedics and Rheumatology, Japanese Red Cross Okayama Hospital, Tokushima National Hospital, Harada Hospital, Yodogawa Christian Hospital, Okayama Saiseikai General Hospital, Higashiosaka City Medical Center, Minamiosaka Hospital. We thank the late Ph.D. Chikuma Hamada, Department of Business Engineering, Faculty of Engineering, Tokyo University of Science, for his statistical consultant. In addition, we thank Linical Co., Ltd.(Osaka, Japan), which supported the executive office, monitoring, audit, and writing assistance for this manuscript, Meditrix Corporation (Tokyo, Japan), which supported data management, SOC Co., Ltd. (Tokyo, Japan), which supported statistical analysis, MICRON Inc. (Tokyo, Japan) which supported the decision office for bone fractures and bone mineral density, and LSI Medience Corporation (Tokyo, Japan), which supported the measurement of bone turnover markers.

Funding

This study was funded by Astellas Pharma Inc. and Ono pharmaceutical Co., LTD.

Author information

Authors and Affiliations

  1. Department of Orthopaedic Surgery and Rheumatology, KINDAI University Nara Hospital, Nara, Japan

    Satoshi Soen

  2. Department of Allergy and Rheumatology, Graduate School of Medicine and Faculty of Medicine, The University of Tokyo, Tokyo, Japan

    Kazuhiko Yamamoto

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

    Tsutomu Takeuchi

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

    Yoshiya Tanaka

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

    Sakae Tanaka

  6. Nagasaki Study Center, The Open University of Japan, Nagasaki, Japan

    Masako Ito

  7. Department of Orthopaedic Surgery, Tamana Central Hospital, Kumamoto, Japan

    Tetsuo Nakano

  8. School of Health ScienceFaculty of Medicine, Tottori University, Tottori, Japan

    Hiroshi Hagino

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

    Akihiro Hirakawa

  10. Fujii Memorial Institute of Medical Sciences, Tokushima University, Tokushima, Japan

    Toshio Matsumoto

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  1. Satoshi Soen
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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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  7. Tetsuo Nakano
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  8. Hiroshi Hagino
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  10. Toshio Matsumoto
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Corresponding author

Correspondence to Satoshi Soen.

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Conflict of interest

S.S. has received consulting fees, speaking fees, and/or honoraria from Asahi Kasei Pharma, Astellas, Chugai, Daiichi-Sankyo, Eisai, Eli Lilly Japan, MSD, Ono, Pfizer, Takeda and Teijin 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. Personal Fee 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 speaking fees 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, speaking 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, speaking fees, honoraria, and/or research funding from Chugai, Astellas, Asahi Kasei Pharma, Daiichi-Sankyo, Eli Lilly Japan, MSD, Ono and Pfizer. H.H. has received lecture fees or grants from Asahi Kasei Pharma, Astellas, Chugai, Eisai, Eli Lilly Japan, Mitsubishi -Tanabe, Mochida, Ono, Pfizer, Taisho Toyama, Takeda, Teijin Pharma, MSD and UCB. A.H. has received consulting fees, speaking fees, honoraria, and/or research funding from Astellas, Ono and Teijin Pharma. T.M. has received consulting fees from Chugai, Amgen Astellas Biopharma, Teijin Pharma, Daiichi-Sankyo and Asahi Kasei Pharma.

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Soen, S., Yamamoto, K., Takeuchi, T. et al. Minodronate combined with alfacalcidol versus alfacalcidol alone for glucocorticoid-induced osteoporosis: a multicenter, randomized, comparative study. J Bone Miner Metab 38, 511–521 (2020). https://doi.org/10.1007/s00774-019-01077-x

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  • DOI: https://doi.org/10.1007/s00774-019-01077-x

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