Journal of Bone and Mineral Metabolism

, Volume 27, Issue 1, pp 66–75 | Cite as

Randomized controlled study on the prevention of osteoporotic fractures (OF study): a phase IV clinical study of 15-mg menatetrenone capsules

  • Tetsuo Inoue
  • Toshiharu Fujita
  • Hideaki Kishimoto
  • Toshitaka Makino
  • Tetsuro Nakamura
  • Toshitaka Nakamura
  • Tosiya Sato
  • Kaoru Yamazaki
Original article


An open-label study with blinded evaluation was performed to compare the preventive effect of a calcium supplement alone (monotherapy) or calcium supplement plus menatetrenone (combined therapy) on fracture in osteoporotic postmenopausal women aged 50 years or older. Patients were randomized to receive monotherapy (n = 2,193) or combined therapy (n = 2,185). Before randomization, the subjects were stratified into a subgroup without vertebral fractures (n = 2,986; no-fracture subgroup) and a subgroup with at least one vertebral fracture (n = 1,392; fracture subgroup). The incidence rate of new vertebral fractures during 36 months of treatment (primary endpoint) did not differ significantly between either subgroup of the two treatment groups. Although the cumulative 48-month incidence rate of new clinical fractures (secondary endpoint) was lower in the combined therapy group, the difference was not significant. There was a lower risk of new vertebral fractures in patients with at least five baseline fractures who received combined therapy. Also, the loss of height was less with combined therapy than with monotherapy among patients 75 years of age or older at enrollment, those whose last menstrual period occurred 30 years or more before enrollment, and those with at least five vertebral fractures at enrollment. Adverse events and adverse reactions were more frequent in the combined therapy group. In conclusion, menatetrenone therapy was not effective for preventing vertebral fractures in the full analysis set of this study, but the results suggested that it may prevent vertebral fractures in patients with more advanced osteoporosis.


Osteoporosis Fractures Menatetrenone Controlled study ADL 



Research funds were provided by the Japanese Ministry of Health, Labor and Welfare for the first 2 years of the study, and thereafter the study was funded by Eisai Co. Ltd. (Tokyo, Japan). We thank all the study participants, physicians, and co-medical staff.


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Copyright information

© The Japanese Society for Bone and Mineral Research and Springer 2008

Authors and Affiliations

  • Tetsuo Inoue
    • 1
  • Toshiharu Fujita
    • 2
  • Hideaki Kishimoto
    • 3
  • Toshitaka Makino
    • 4
  • Tetsuro Nakamura
    • 5
  • Toshitaka Nakamura
    • 6
  • Tosiya Sato
    • 7
  • Kaoru Yamazaki
    • 8
  1. 1.Aoyama General HospitalKosakaiJapan
  2. 2.Department of Data ScienceInstitute of Statistical MathematicsMinato-kuJapan
  3. 3.Department of OrthopedicsSan-in Rosai HospitalYonagoJapan
  4. 4.Japan Cosmetic Industry AssociationTokyoJapan
  5. 5.Institute for Medical Science of AgingTokyoJapan
  6. 6.Department of Orthopedic SurgeryUniversity of Occupational and Environmental HealthKitakyushuJapan
  7. 7.Department of BiostatisticsKyoto University School of Public HealthKyotoJapan
  8. 8.Department of Orthopaedic SurgeryHamamatsu University School of MedicineHamamatsuJapan

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