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A double-blind dose-ranging study of risedronate in Japanese patients with osteoporosis (a study by the Risedronate Late Phase II Research Group)

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Abstract

To determine the clinical recommended dosage regimen of risedronate for the treatment of involutional osteoporosis in Japanese patients, dose-response relationships for the efficacy and safety of this drug were investigated using a multi-center, randomized, double-blind, parallel group comparative design with four dose levels of risedronate (placebo, 1 mg, 2.5 mg and 5 mg per day). A total of 211 patients diagnosed with involutional osteoporosis according to the criteria proposed by the Japanese Society for Bone and Mineral Research were randomized and received one of the four doses once daily for 36 weeks. All patients were supplemented with 200 mg of calcium daily in the form of calcium lactate. The primary efficacy endpoint was the percent change in bone mineral density of the lumbar spine (L2–L4 BMD) determined by dual-energy X-ray absorptiometry (DXA) from baseline to the time of final evaluation. Changes in biochemical markers of bone turnover and safety profile were also compared. Percent changes in L2–L4 BMD at final evaluation in the placebo, and 1-, 2.5-, and 5-mg risedronate groups were 0.79±5.30, 2.71±4.93, 5.29±3.96, and 5.15±4.25% (mean±SD), respectively. A linear dose-response relationship was obtained up to a dose of 2.5 mg, whereas no further increase in BMD was observed at 5 mg. The decrease in bone turnover markers, including N-terminal osteocalcin, phosphorus, and urinary deoxypyridinoline, also showed a linear dose-response relationship up to a dose of 2.5 mg. Alkaline phosphatase level decreased linearly up to a dose of 5 mg. Risedronate was well tolerated in this 36-week study with 1- to 5-mg doses. Neither the overall incidence of adverse events nor the percentage of patients without problem in overall safety assessment differed significantly among the dose groups including the placebo group. Based on these results, a once-daily dose of 2.5 mg of risedronate, which is half that used in Caucasians, is recommended for the treatment of involutional osteoporosis in Japanese patients.

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Authors and Affiliations

  1. Research Institute and Practice for Involutional Diseases, 1610-1 Meisei, Misato-Mura, 399-8101, Minamiazumi-gun, Nagano Prefecture, Japan

    M. Shiraki

  2. Department of Nuclear Medicine, Kawasaki Medical School, Kurashiki, Okayama, Japan

    M. Fukunaga

  3. Department of Orthopedic Surgery, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan

    K. Kushida & T. Inoue

  4. Department of Orthopedic Surgery, Faculty of Medicine, Tottori University, Yonago, Tottori, Japan

    H. Kishimoto & K. Yamamoto

  5. Department of Obstetrics and Gynecology, Faculty of Medicine, The University of Tokyo, Tokyo, Japan

    Y. Taketani

  6. Department of Obstetrics and Gynecology, Yokohama City University School of Medicine, Yokohama, Japan

    H. Minaguchi

  7. Department of Radiology, Shiga University of Medical Science, Ohtsu, Shiga, Japan

    R. Morita

  8. Second Department of Internal Medicine, Osaka City University Medical School, Osaka, Japan

    H. Morii

  9. Department of Biostatistics, School of Health Sciences and Nursing, The University of Tokyo, Tokyo, Japan

    Y. Ohashi

  10. Ministry of Finance Tokyo Hospital, Tokyo, Japan

    H. Orimo

  11. Department of Orthopedics, San-in Rosai Hospital, Yonago, Tottori , Japan

    H. Kishimoto

  12. The University of Tokyo Hospital, Tokyo, Japan

    Y. Taketani

  13. Minaguchi Hospital, Tokyo , Japan

    H. Minaguchi

  14. Houmikai Aoyama General Hospital, Hoi-gun, Aichi , Japan

    T. Inoue

  15. Shiga University of Medical Science Hospital, Ohtsu, Shiga , Japan

    R. Morita

  16. Osaka City University Medical School, Osaka, Japan

    H. Morii

  17. Department of Orthopedics, Hakuai Hospital, Yonago, Tottori , Japan

    K. Yamamoto

  18. Tokyo Metropolitan Geriatric Hospital, Tokyo, Japan

    H. Orimo

Authors
  1. M. Shiraki
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  2. M. Fukunaga
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  3. K. Kushida
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  4. H. Kishimoto
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  5. Y. Taketani
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  6. H. Minaguchi
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  7. T. Inoue
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  8. R. Morita
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  9. H. Morii
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  10. K. Yamamoto
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  11. Y. Ohashi
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  12. H. Orimo
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Appendix

Appendix

Committee Members of the Risedronate Late Phase II Study Group

The committee members of the Risedronate Late Phase II Study Group are:

  • Principal Investigator: H. Orimo

  • Steering Committee: Y. Taketani, H. Minaguchi, T. Inoue, R. Morita, H. Morii, K. Yamamoto

  • Central Assessment Committee: K. Kushida, M. Shiraki, M. Fukunaga, H. Kishimoto

  • Controller: Y. Ohashi

Other members of the Risedronate Late Phase II Study Group

The remaining members of the study group are listed in Table 4.

Table 4. Members of the Risedronate Late Phase II Study Group
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Shiraki, M., Fukunaga, M., Kushida, K. et al. A double-blind dose-ranging study of risedronate in Japanese patients with osteoporosis (a study by the Risedronate Late Phase II Research Group). Osteoporos Int 14, 225–234 (2003). https://doi.org/10.1007/s00198-002-1369-9

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  • DOI: https://doi.org/10.1007/s00198-002-1369-9

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