Osteoporosis International

, Volume 14, Issue 3, pp 225–234 | Cite as

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

  • M. Shiraki
  • M. Fukunaga
  • K. Kushida
  • H. Kishimoto
  • Y. Taketani
  • H. Minaguchi
  • T. Inoue
  • R. Morita
  • H. Morii
  • K. Yamamoto
  • Y. Ohashi
  • H. Orimo
Original Article


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.


Bone mineral density Dose response Osteoporosis Risedronate 


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Copyright information

© International Osteoporosis Foundation and National Osteoporosis Foundation 2003

Authors and Affiliations

  • M. Shiraki
    • 1
  • M. Fukunaga
    • 2
  • K. Kushida
    • 3
  • H. Kishimoto
    • 4
    • 11
  • Y. Taketani
    • 5
    • 12
  • H. Minaguchi
    • 6
    • 13
  • T. Inoue
    • 3
    • 14
  • R. Morita
    • 7
    • 15
  • H. Morii
    • 8
    • 16
  • K. Yamamoto
    • 4
    • 17
  • Y. Ohashi
    • 9
  • H. Orimo
    • 10
    • 18
  1. 1.Research Institute and Practice for Involutional DiseasesMinamiazumi-gun, Nagano PrefectureJapan
  2. 2.Department of Nuclear MedicineKawasaki Medical SchoolOkayamaJapan
  3. 3.Department of Orthopedic SurgeryHamamatsu University School of MedicineShizuokaJapan
  4. 4.Department of Orthopedic Surgery, Faculty of MedicineTottori UniversityTottoriJapan
  5. 5.Department of Obstetrics and Gynecology, Faculty of MedicineThe University of TokyoTokyoJapan
  6. 6.Department of Obstetrics and GynecologyYokohama City University School of MedicineYokohamaJapan
  7. 7.Department of RadiologyShiga University of Medical ScienceShigaJapan
  8. 8.Second Department of Internal MedicineOsaka City University Medical SchoolOsakaJapan
  9. 9.Department of Biostatistics, School of Health Sciences and NursingThe University of TokyoTokyoJapan
  10. 10.Ministry of Finance Tokyo HospitalTokyoJapan
  11. 11.Department of OrthopedicsSan-in Rosai HospitalTottori Japan
  12. 12.The University of Tokyo HospitalTokyoJapan
  13. 13.Minaguchi HospitalTokyo Japan
  14. 14.Houmikai Aoyama General HospitalAichi Japan
  15. 15.Shiga University of Medical Science HospitalShiga Japan
  16. 16.Osaka City University Medical SchoolOsakaJapan
  17. 17.Department of OrthopedicsHakuai HospitalTottori Japan
  18. 18.Tokyo Metropolitan Geriatric HospitalTokyoJapan

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