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.
RCT Entities:
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.
Authors: D L Lacey; H L Tan; J Lu; S Kaufman; G Van; W Qiu; A Rattan; S Scully; F Fletcher; T Juan; M Kelley; T L Burgess; W J Boyle; A J Polverino Journal: Am J Pathol Date: 2000-08 Impact factor: 4.307
Authors: D L Lacey; E Timms; H L Tan; M J Kelley; C R Dunstan; T Burgess; R Elliott; A Colombero; G Elliott; S Scully; H Hsu; J Sullivan; N Hawkins; E Davy; C Capparelli; A Eli; Y X Qian; S Kaufman; I Sarosi; V Shalhoub; G Senaldi; J Guo; J Delaney; W J Boyle Journal: Cell Date: 1998-04-17 Impact factor: 41.582
Authors: Marc C Hochberg; Susan Greenspan; Richard D Wasnich; Paul Miller; Desmond E Thompson; Philip D Ross Journal: J Clin Endocrinol Metab Date: 2002-04 Impact factor: 5.958
Authors: H Yasuda; N Shima; N Nakagawa; K Yamaguchi; M Kinosaki; S Mochizuki; A Tomoyasu; K Yano; M Goto; A Murakami; E Tsuda; T Morinaga; K Higashio; N Udagawa; N Takahashi; T Suda Journal: Proc Natl Acad Sci U S A Date: 1998-03-31 Impact factor: 11.205
Authors: Kaisa K Ivaska; Paul Gerdhem; H Kalervo Väänänen; Kristina Akesson; Karl J Obrant Journal: J Bone Miner Res Date: 2010-02 Impact factor: 6.741
Authors: Socrates Papapoulos; Roland Chapurlat; Cesar Libanati; Maria Luisa Brandi; Jacques P Brown; Edward Czerwiński; Marc-Antoine Krieg; Zulema Man; Dan Mellström; Sebastião C Radominski; Jean-Yves Reginster; Heinrich Resch; José A Román Ivorra; Christian Roux; Eric Vittinghoff; Matthew Austin; Nadia Daizadeh; Michelle N Bradley; Andreas Grauer; Steven R Cummings; Henry G Bone Journal: J Bone Miner Res Date: 2012-03 Impact factor: 6.741
Authors: Henry G Bone; Roland Chapurlat; Maria-Luisa Brandi; Jacques P Brown; Edward Czerwinski; Marc-Antoine Krieg; Dan Mellström; Sebastião C Radominski; Jean-Yves Reginster; Heinrich Resch; Jose A Román Ivorra; Christian Roux; Eric Vittinghoff; Nadia S Daizadeh; Andrea Wang; Michelle N Bradley; Nathalie Franchimont; Michelle L Geller; Rachel B Wagman; Steven R Cummings; Socrates Papapoulos Journal: J Clin Endocrinol Metab Date: 2013-08-26 Impact factor: 5.958
Authors: Rena J Eudy-Byrne; William Gillespie; Matthew M Riggs; Marc R Gastonguay Journal: J Pharmacokinet Pharmacodyn Date: 2017-10-28 Impact factor: 2.745
Authors: David W Dempster; Hua Zhou; Robert R Recker; Jacques P Brown; Christopher P Recknor; E Michael Lewiecki; Paul D Miller; Sudhaker D Rao; David L Kendler; Robert Lindsay; John H Krege; Jahangir Alam; Kathleen A Taylor; Boris Janos; Valerie A Ruff Journal: J Clin Endocrinol Metab Date: 2016-02-09 Impact factor: 5.958
Authors: Sarah Davis; Emma Simpson; Jean Hamilton; Marrissa Martyn-St James; Andrew Rawdin; Ruth Wong; Edward Goka; Neil Gittoes; Peter Selby Journal: Health Technol Assess Date: 2020-06 Impact factor: 4.014