Original article

Journal of Bone and Mineral Metabolism

, Volume 27, Issue 1, pp 66-75

First online:

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

  • Tetsuo InoueAffiliated withAoyama General Hospital
  • , Toshiharu FujitaAffiliated withDepartment of Data Science, Institute of Statistical Mathematics Email author 
  • , Hideaki KishimotoAffiliated withDepartment of Orthopedics, San-in Rosai Hospital
  • , Toshitaka MakinoAffiliated withJapan Cosmetic Industry Association
  • , Tetsuro NakamuraAffiliated withInstitute for Medical Science of Aging
  • , Toshitaka NakamuraAffiliated withDepartment of Orthopedic Surgery, University of Occupational and Environmental Health
  • , Tosiya SatoAffiliated withDepartment of Biostatistics, Kyoto University School of Public Health
  • , Kaoru YamazakiAffiliated withDepartment of Orthopaedic Surgery, Hamamatsu University School of Medicine

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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