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

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Abstract

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.

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Acknowledgments

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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Authors and Affiliations

  1. Aoyama General Hospital, Kosakai, Japan

    Tetsuo Inoue

  2. Department of Data Science, Institute of Statistical Mathematics, 4-6-7 Minamiazabu, Minato-ku, Tokyo, 106-8569, Japan

    Toshiharu Fujita

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

    Hideaki Kishimoto

  4. Japan Cosmetic Industry Association, Tokyo, Japan

    Toshitaka Makino

  5. Institute for Medical Science of Aging, Tokyo, Japan

    Tetsuro Nakamura

  6. Department of Orthopedic Surgery, University of Occupational and Environmental Health, Kitakyushu, Japan

    Toshitaka Nakamura

  7. Department of Biostatistics, Kyoto University School of Public Health, Kyoto, Japan

    Tosiya Sato

  8. Department of Orthopaedic Surgery, Hamamatsu University School of Medicine, Hamamatsu, Japan

    Kaoru Yamazaki

Authors
  1. Tetsuo Inoue
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  2. Toshiharu Fujita
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  3. Hideaki Kishimoto
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  4. Toshitaka Makino
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  5. Tetsuro Nakamura
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  6. Toshitaka Nakamura
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  7. Tosiya Sato
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  8. Kaoru Yamazaki
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Corresponding author

Correspondence to Toshiharu Fujita.

Appendix

Appendix

The following individuals and organizations (chairmen are indicated by asterisks) were responsible for the design, execution, analysis, and reporting of this study: Steering/Management Committee (Tetsuo Inoue*, Hideaki Takahashi, Hiroshi Minaguchi, Hirotoshi Morii, Kaoru Yamazaki, Keiro Ono, Kichizo Yamamoto, Kiyoshi Kaneda, Shoichi Kokubun, Tadashi Funakoshi, Toshiharu Fujita, Toshitaka Nakamura, Tosiya Sato, and Yukihide Iwamoto); Protocol/Study Design Committee (Kaoru Yamazaki*, Tatsuhiko Tanizawa, Toshiharu Fujita, and Tosiya Sato); Case Review Committee (Tetsuro Nakamura*, Hiroshi Minaguchi, Kaoru Yamazaki, Tetsuo Inoue, and Toshiharu Fujita); Data Management/Study Execution Committee (Toshiharu Fujita*, Atsuya Ono, Kaoru Yamazaki, Tadataka Mitsuishi, Tetsuro Nakamura, Toshitaka Makino, and Tosiya Sato); Radiological Evaluation Committee (Kazuhiro Kushida*, Akira Kitazawa, Hideaki Kishimoto, Hiroshi Hagino, Hiroshi Katagiri, and Tsuyoshi Oishi); and Ethical/Monitoring Committee (Hiroe Tsubaki*, Akira Itabashi, Kiyoshi Kurokawa, Takahide Kurokawa, Tatsuo Kuroyanagi, and Yoichi Kato).

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Inoue, T., Fujita, T., Kishimoto, H. et al. Randomized controlled study on the prevention of osteoporotic fractures (OF study): a phase IV clinical study of 15-mg menatetrenone capsules. J Bone Miner Metab 27, 66–75 (2009). https://doi.org/10.1007/s00774-008-0008-8

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  • DOI: https://doi.org/10.1007/s00774-008-0008-8

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