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)

详细信息    查看全文

• 作者：T. Sugimoto ; T. Matsumoto ; T. Hosoi ; T. Miki ; I. Gorai…
• 关键词：Bone mineral density ; Bone turnover marker ; Denosumab ; Fracture ; Japanese ; Long ; term ; Osteoporosis
• 刊名：Osteoporosis International
• 出版年：2015
• 出版时间：February 2015
• 年：2015
• 卷：26
• 期：2
• 页码：765-774
• 全文大小：659 KB
• 参考文献：1. NIH (2001) Consensus conference (2001) osteoporosis prevention, diagnosis, and therapy. JAMA 285:785-95 CrossRef
  2. Hochberg MC, Greenspan S, Wasnich RD, Miller P, Thompson DE, Ross PD (2002) Changes in bone density and turnover explain the reductions in incidence of nonvertebral fractures that occur during treatment with antiresorptive agents. J Clin Endocrinol Metab 87(4):1586-592 CrossRef
  3. Ivaska KK, Gerdhem P, V??n?nen HK, Akesson K, Obrant KJ (2010) Bone turnover markers and prediction of fracture: a prospective follow-up study of 1040 elderly women for a mean of 9?years. J Bone Miner Res 25(2):393-03 CrossRef
  4. Fuller K, Wong B, Fox S, Choi Y, Chambers TJ (1998) TRANCE is necessary and sufficient for osteoblast-mediated activation of bone resorption in osteoclasts. J Exp Med 188(5):997-001 CrossRef
  5. Lacey DL, Tan HL, Lu J, Kaufman S, Van G, Qiu W, Rattan A, Scully S, Fletcher F, Juan T, Kelley M, Burgess TL, Boyle WJ, Polverino AJ (2000) Osteoprotegerin ligand modulates murine osteoclast survival in vitro and in vivo. Am J Pathol 157(2):435-48 CrossRef
  6. Lacey DL, Timms E, Tan HL, Kelley MJ, Dunstan CR, Burgess T, Elliott R, Colombero A, Elliott G, Scully S, Hsu H, Sullivan J, Hawkins N, Davy E, Capparelli C, Eli A, Qian YX, Kaufman S, Sarosi I, Shalhoub V, Senaldi G, Guo J, Delaney J, Boyle WJ (1998) Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation. Cell 93(2):165-76 CrossRef
  7. Yasuda H, Shima N, Nakagawa N, Yamaguchi K, Kinosaki M, Mochizuki S, Tomoyasu A, Yano K, Goto M, Murakami A, Tsuda E, Morinaga T, Higashio K, Udagawa N, Takahashi N, Suda T (1998) Osteoclast differentiation factor is a ligand for osteoprotegerin/osteoclastogenesis-inhibitory factor and is identical to TRANCE/RANKL. Proc Natl Acad Sci U S A 95(7):3597-602 CrossRef
  8. Cummings SR, Martin JS, McClung MR, Siris ES, Eastell R, Reid IR, Delmas P, Zoog HB, Austin M, Wang A, Kutilek S, Adami S, Christiansen C (2009) Denosumab for prevention of fractures in postmenopausal women with osteoporosis. N Engl J Med 361:756-65 CrossRef
  9. Papapoulos S, Chapurlat R, Libanati C, Brandi ML, Brown JP, Czerwinski E, Krieg M-A, Man Z, Mellstrom D, Radominski SC, Reginster J-Y, Resch H, Ivorra JAR, Roux C, Vittinghoff E, Austin M, Daizadeh N, Bradley MN, Grauer A, Cummings SR, Bone HG (2012) Five years of denosumab exposure in women with postmenopausal osteoporosis: results from the first two years of the FREEDOM extension. J Bone Miner Res 27(3):694-01 CrossRef
  10. Bone HG, Chapurlat R, Brandi ML, Brown JP, Czerwinski E, Krieg MA, Mellstr?m D, Radominski SC, Reginster JY, Resch H, Ivorra JA, Roux C, Vittinghoff E, Daizadeh NS, Wang A, Bradley MN, Franchimont N, Geller ML, Wagman RB, Cummings SR, Papapoulos S (2013) The effect of three or six years of denosumab exposure in women with postmenopausal osteoporosis: results from the FREEDOM extension. J Clin Endocrinol Metab 98(11):4483-492 CrossRef
  11. Papapoulos S, Lippuner K, Roux C, Hall J, Kendler D, Lewiecki EM, Brandi ML, Czerwiński E, Franek E, Lakatos P, Mautalen C, Minisola S, Reginster JY, Jensen S, Daizadeh N, Wang A, Geller M, Wagman RB, Bone HG (2013) Eight Years of Denosumab Treatment in Postmenopausal Women With Osteoporosis: Results From the First Five Years of the FREEDOM Extension [Abstract LB-MO26] American Society for Bone and Mineral Research 2013 Annual Meeting
  12. Nakamura T, Matsumoto T, Sugimoto T, Hosoi T, Miki T, Gorai I, Yoshikawa H, Tanaka Y, Tanaka S, Sone T, Nakano T, Ito M, Matsui S, Yoneda T, Takami H, Watanabe K, Osakabe T, Shiraki M, Fukunaga M (2014) Fracture risk reduction with denosumab in Japanese postmenopausal women and men with osteoporosis: denosumab fracture intervention r
• 刊物类别：Medicine
• 刊物主题：Medicine & Public Health
  Orthopedics
  Gynecology
  Endocrinology
  Rheumatology
  
• 出版者：Springer London
• ISSN：1433-2965

文摘

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.