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01-02-2015 | Original Article

Three-year denosumab treatment in postmenopausal Japanese women and men with osteoporosis: results from a 1-year open-label extension of the Denosumab Fracture Intervention Randomized Placebo Controlled Trial (DIRECT)

Authors: T. Sugimoto, T. Matsumoto, T. Hosoi, T. Miki, I. Gorai, H. Yoshikawa, Y. Tanaka, S. Tanaka, M. Fukunaga, T. Sone, T. Nakano, M. Ito, S. Matsui, T. Yoneda, H. Takami, K. Watanabe, T. Osakabe, N. Okubo, M. Shiraki, T. Nakamura

Published in: Osteoporosis International | Issue 2/2015

Abstract

Summary

A 12-month extension phase of DIRECT in Japanese subjects with osteoporosis showed that total 3 years of denosumab treatment in Japanese postmenopausal women and men with osteoporosis was associated with low fracture rates, persistent bone turnover marker (BTM) reductions, continuous bone mineral density (BMD) increases, and a favorable overall benefit/risk profile.

Introduction

The DIRECT trial demonstrated that 2 years of treatment with denosumab 60 mg subcutaneously every 6 months significantly reduced the incidence of vertebral fracture compared to placebo in Japanese postmenopausal women and men with osteoporosis. The purpose of this study is to evaluate the efficacy and safety of denosumab treatment for up to 3 years.

Methods

This study includes a 2-year randomized, double-blind, placebo-controlled phase and a 1-year open-label extension phase in which all subjects received denosumab. The data correspond to 3 years of denosumab treatment in subjects who received denosumab (long-term group) and 1 year of denosumab treatment in subjects who received placebo (cross-over group) in the double-blind phase.

Results

Eight hundred and ten subjects who completed the double-blind phase enrolled into the extension phase, and 775 subjects completed the study. All subjects received denosumab with daily supplements of calcium and vitamin D. The cumulative 36-month incidences of new or worsening vertebral fractures and new vertebral fractures were 3.8 and 2.5 %, respectively, in the long-term group. In this group, the BMD continued to increase, and the reduction in BTMs was maintained. In the cross-over group, comparable BMD increases and BTMs reductions to those of in their first year of the long-term group were confirmed. Adverse events did not show a notable increase with long-term denosumab administration. One event of osteonecrosis of the jaw occurred in the cross-over group.

Conclusions

Three-year denosumab treatment in Japanese subjects with osteoporosis showed a favorable benefit/risk profile.

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Title: Three-year denosumab treatment in postmenopausal Japanese women and men with osteoporosis: results from a 1-year open-label extension of the Denosumab Fracture Intervention Randomized Placebo Controlled Trial (DIRECT)
Authors: T. Sugimoto
T. Matsumoto
T. Hosoi
T. Miki
I. Gorai
H. Yoshikawa
Y. Tanaka
S. Tanaka
M. Fukunaga
T. Sone
T. Nakano
M. Ito
S. Matsui
T. Yoneda
H. Takami
K. Watanabe
T. Osakabe
N. Okubo
M. Shiraki
T. Nakamura
Publication date: 01-02-2015
Publisher: Springer London
Published in: Osteoporosis International / Issue 2/2015
Print ISSN: 0937-941X
Electronic ISSN: 1433-2965
DOI: https://doi.org/10.1007/s00198-014-2964-2

At a glance: The STEP trials

Springer Medicine

Three-year denosumab treatment in postmenopausal Japanese women and men with osteoporosis: results from a 1-year open-label extension of the Denosumab Fracture Intervention Randomized Placebo Controlled Trial (DIRECT)

Abstract

Summary

Introduction

Methods

Results

Conclusions

At a glance: The STEP trials

Springer Medicine

Abstract

Summary

Introduction

Methods

Results

Conclusions

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