The Effect of Three or Six Years of Denosumab Exposure in Women With Postmenopausal Osteoporosis: Results From the FREEDOM Extension

被引：202

作者：

Bone, Henry G. ^{[1
]}

Chapurlat, Roland ^{[2
,3
]}

Brandi, Maria-Luisa ^{[4
]}

Brown, Jacques P. ^{[5
,6
]}

Czerwinski, Edward ^{[7
]}

Krieg, Marc-Antoine ^{[8
]}

Mellstrom, Dan ^{[9
]}

Radominski, Sebastiao C. ^{[10
]}

Reginster, Jean-Yves ^{[11
]}

Resch, Heinrich ^{[12
]}

Roman Ivorra, Jose A. ^{[13
]}

Roux, Christian ^{[14
]}

Vittinghoff, Eric ^{[15
]}

Daizadeh, Nadia S. ^{[16
]}

Wang, Andrea ^{[16
]}

Bradley, Michelle N. ^{[16
]}

Franchimont, Nathalie ^{[16
]}

Geller, Michelle L. ^{[16
]}

Wagman, Rachel B. ^{[16
]}

Cummings, Steven R. ^{[15
,17
]}

Papapoulos, Socrates ^{[18
]}

机构：

[1] Michigan Bone & Mineral Clin, Detroit, MI 48236 USA

[2] Hop Edouard Herriot, INSERM, UMR 1033, F-69437 Lyon, France

[3] Univ Lyon, F-69437 Lyon, France

[4] Univ Florence, I-50139 Florence, Italy

[5] Ctr Hosp Univ Quebec, Ctr Rech, Quebec City, PQ G1V 4G2, Canada

[6] Univ Laval, Fac Med, Dept Med, Quebec City, PQ G1V 4G2, Canada

[7] Krakow Med Ctr, PL-31501 Krakow, Poland

[8] Univ Lausanne Hosp, CH-1011 Lausanne, Switzerland

[9] Sahlgrens Univ Hosp, S-41132 Gothenburg, Sweden

[10] Univ Fed Parana, BR-80060000 Curitiba, Parana, Brazil

[11] Univ Liege, B-4020 Liege, Belgium

[12] St Vincent Hosp, A-1060 Vienna, Austria

[13] Hosp Univ La Fe, Valencia 46026, Spain

[14] Paris Descartes Univ, F-75014 Paris, France

[15] Univ Calif San Francisco, San Francisco, CA 94107 USA

[16] Amgen Inc, Thousand Oaks, CA 91320 USA

[17] Calif Pacific Med Ctr, Res Inst, San Francisco Coordinating Ctr, San Francisco, CA 94107 USA

[18] Leiden Univ, Med Ctr, NL-2333 RC Leiden, Netherlands

来源：

JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM | 2013年 / 98卷 / 11期

关键词：

BONE-MINERAL DENSITY; FRACTURES; RANKL;

D O I：

10.1210/jc.2013-1597

中图分类号：

R5 [内科学];

学科分类号：

100201 [内科学];

摘要：

Context: The Fracture Reduction Evaluation of Denosumab in Osteoporosis Every 6 Months (FREEDOM) extension is evaluating the long-term efficacy and safety of denosumab for up to 10 years. Objective: The objective of the study was to report results from the first 3 years of the extension, representing up to 6 years of denosumab exposure. Design, Setting, and Participants: This was a multicenter, international, open-label study of 4550 women. Intervention: Women from the FREEDOM denosumab group received 3 more years of denosumab for a total of 6 years (long-term) and women from the FREEDOM placebo group received 3 years of denosumab (crossover). Main Outcome Measures: Bone turnover markers (BTMs), bone mineral density (BMD), fracture, and safety data are reported. Results: Reductions in BTMs were maintained (long-term) or achieved rapidly (crossover) after denosumab administration. In the long-term group, BMD further increased for cumulative 6-year gains of 15.2% (lumbar spine) and 7.5% (total hip). During the first 3 years of denosumab treatment, the crossover group had significant gains in lumbar spine (9.4%) and total hip (4.8%) BMD, similar to the long-term group during the 3-year FREEDOM trial. In the long-term group, fracture incidences remained low and below the rates projected for a virtual placebo cohort. In the crossover group, 3-year incidences of new vertebral and nonvertebral fractures were similar to those of the FREEDOM denosumab group. Incidence rates of adverse events did not increase over time. Six participants had events of osteonecrosis of the jaw confirmed by adjudication. One participant had a fracture adjudicated as consistent with atypical femoral fracture. Conclusion: Denosumab treatment for 6 years remained well tolerated, maintained reduced bone turnover, and continued to increase BMD. Fracture incidence remained low.

引用

页码：4483 / 4492

页数：10

共 18 条

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[2]

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