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Three years of treatment with minodronate in patients with postmenopausal osteoporosis

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Abstract

The objective of this study was to determine the safety and efficacy of long-term minodronate treatment in women with postmenopausal osteoporosis based on re-analysis of a phase III 2-year clinical trial with a 1-year extension. Women aged 55–80 years old with fragility fractures were enrolled and randomized to take 1 mg minodronate or placebo once a day in the original 2-year study. The subjects who completed the 2-year study were invited to participate in an additional 1-year extension in which all subjects were to receive minodronate. Finally, a total 380 subjects completed the extension study (186 from the placebo group and 194 from the minodronate group). Fracture results observed in the extension study were consistent with those observed in the first 2 years in minodronate group. In contrast, the placebo/minodronate group showed a decreased incidence of new vertebral fractures during year 3 compared to that in year 2. In the patients who received minodronate in the original 2-year study, lumbar bone mineral density (BMD) increased consistently during year 3 and bone turnover markers decreased within the first 6 months and remained constant thereafter over 3 years. Similar positive effects of minodronate on BMD and bone turnover markers occurred when therapy was initiated in the placebo/minodronate group. No new safety concerns observed during the extension period compared to the safety observations made during the 2-year study. It was concluded that daily administration of 1 mg oral minodronate is safe and well tolerated, and that the efficacy of this dose in reducing vertebral fracture risk in postmenopausal women over 2 years is sustained with continuing treatment.

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Acknowledgments

We thank Dr. H. Morii, Osaka City University Medical School, Osaka, Japan, and clinical sites in Japan that participated in this study: T. Ota, Ota Orthopedic Clinic; M. Kokaji, M. Tsuji, S. Kawamura, Kobayashi Hospital; T. Hashimoto, Hakodate Koseiin Hakodate Central General Hospital; S. Sato, Eniwa Hospital; G. Katahira, Sapporo Kiyota Orthopaedic Hospital; Y. Saito, Hokuei Orthopedics; T. Fukunaga, Ainosato Orthopedics; T. Ando, Morioka Hospital; S. Tsukikawa, Tsukikawa Lady’s Clinic; S. Harada, Tsukuba Gakuen Hospital; N. Tajima, Tajima Geka Ichouka; K. Ogata, Seiwakai Shoda Hospital; T. Michimata, Uchibori Seikeigeka Iin; H. Inoue, Inoue Hospital; M. Inuzuka, Chousei Hospital; S. Ichikawa, Cardiovascular Hospital of Central Japan; K. Toba, Toba Orthopedic Clinic; Y. Kaneda, Kaneda Orthopedics; S. Yamada, Kyoai Clinic; K. Fukuda, Shiratori Clinic; A. Yamaguchi, Yamaguchi Hospital; T. Nakamura, Abe Clinic; K. Maruyama, Gate Town Hospital; T. Nakagawa, Senpo Tokyo Takanawa Hospital; T. Takemoto, Misyuku Hospital; K. Kamada, Kumegawa Hospital; S. Yamaguchi, Gonohashi Clinic; C. Nokubo, Nokubo Orthopedic Clinic; M. Takemoto, Takemoto Orthopedics; T. Ishihara, Shirahigebashi Hospital; Y. Tsuruta, Tsuruta Clinic; S. Yamazaki, Sengoku Hospital; T. Ishibashi, T. Okubo, Oguchi East Hospital; Y. Mikami, Yokohama Rosai Hospital; I. Miyata, Aoba Orthopedics Clinic; M. Kasuga, Kasuga Orthopedics; N. Nagata, Nagata Orthopedics; Y. Murai, Murai Orthopedic Iin; S. Noto, Noto Orthopedics; M. Katsumi, Katsumi Orthopedics; H. Morishita, T. Takino, Kanazawa Social Insurance Hospital; N. Hachisuka, Hachisuka Orthopedics; M. Takimori, Nirasaki Mutual Hospital; Y. Nagasaka, Nagasaka Orthopedics; M. Suzuki, Suzuki Orthopedic Iin; S. Kumaki, Hokushin General Hospital; T. Hanaoka, Yamabe Spa Hanaoka Orthopedics; H. Misawa, Yodakubo Hospital; M. Shiraki, Research Institute and Practice for Involutional Diseases; S. Tsuboi, Shizuoka Kosei Hospital; K. Yamazaki, Hamamatsu University School of Medicine University Hospital; M. Taniguchi, Taniguchi Orthopedic Iin; M. Fukuchi, Aobadai Fukuchi Orthopedics and Gastroenterology Clinic; M. Denda, Denda Orthopedics; Y. Nishijima, Nishijima Hospital; Y. Osaka, Minamiosaka Hospital; A. Tei, Kishiwada Tokushukai Hospital; N. Sha, Kanebo Memorial Hospital; C. Terada, Ako Central Hospital; J. Sako, Irie Hospital; Y. Higashi, Himeji Central Hospital; T. Onishi, Onishi Orthopedics; T. Matsubara, Matsubara Clinic; Y. Koyama, K. Atsui, Matsubara Mayflower Hospital; M. Ozaki, Kitade Hospital; M. Ohama, Yonago East Hospital; H. Sanada, Sanada Hospital; K. Sanuki, Sanuki Orthopedic and Rheumatic Clinic; T. Taguchi, Yamaguchi University Hospital; S. Yamagata, Yamagata Iin; K. Nobutani, Sea Side Hospital; H. Yamazaki, H. Ueno, H. Murata, Y. Tanigawa, Mine City Hospital; S. Ono, Marugame Ono Clinic; T. Ogata, Ogata Orthopedic Hospital; H. Ikematsu, Haradoi Hospital; A. Iwaki, K. Domen, Okabe Hospital; Y. Ishibashi, Ishibashi Orthopedics; T. Tsuruta, Tsuruta Orthopaedic Clinic; H. Shibata, Shibata Chokodo Hospital; T. Segata, Kumamoto Saishunso National Hospital; T. Naono, Oita Oka Hospital; E. Nakamura, Nakamura Hospital; S. Okamoto, Sanyo Osteoporosis Research Foundation Okamoto Naika Clinic. The present study was sponsored by Ono Pharmaceutical Co., Ltd. and Astellas Pharma Inc.

Conflict of interest

None of the authors are or were employed by Astellas Pharmaceutical or Ono Pharmaceutical.

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Authors and Affiliations

  1. School of Health Science, Tottori University Faculty of Medicine, Tottori, Japan

    Hiroshi Hagino

  2. Research Institute and Practice for Involutional Diseases, Nagano, Japan

    Masataka Shiraki

  3. Kawasaki Medical School, Okayama, Japan

    Masao Fukunaga

  4. Tamana Central Hospital, Kumamoto, Japan

    Tetsuo Nakano

  5. Hanwa Joint Reconstruction Center Hospital, Osaka, Japan

    Kunio Takaoka

  6. Department of Biostatistics, School of Public Health, University of Tokyo, Tokyo, Japan

    Yasuo Ohashi

  7. Department of Orthopedic Surgery, University of Occupational and Environmental Health, Fukuoka, Japan

    Toshitaka Nakamura

  8. Department of Medicine and Bioregulatory Sciences, University of Tokushima Graduate School of Medical Science, Tokushima, Japan

    Toshio Matsumoto

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  1. Hiroshi Hagino
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  2. Masataka Shiraki
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  3. Masao Fukunaga
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  4. Tetsuo Nakano
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  5. Kunio Takaoka
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  6. Yasuo Ohashi
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  7. Toshitaka Nakamura
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  8. Toshio Matsumoto
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Correspondence to Hiroshi Hagino.

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Hagino, H., Shiraki, M., Fukunaga, M. et al. Three years of treatment with minodronate in patients with postmenopausal osteoporosis. J Bone Miner Metab 30, 439–446 (2012). https://doi.org/10.1007/s00774-011-0332-2

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  • DOI: https://doi.org/10.1007/s00774-011-0332-2

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