A Randomized, Double-Blind Phase 2 Clinical Trial of Blosozumab, a Sclerostin Antibody, in Postmenopausal Women with Low Bone Mineral Density

被引：216

作者：

Recker, Robert R. ^{[1
]}

Benson, Charles T. ^{[2
]}

Matsumoto, Toshio ^{[3
]}

Bolognese, Michael A. ^{[4
]}

Robins, Deborah A. ^{[2
]}

Alam, Jahangir ^{[2
]}

Chiang, Alan Y. ^{[2
]}

Hu, Leijun ^{[2
]}

Krege, John H. ^{[2
]}

Sowa, Hideaki ^{[5
]}

Mitlak, Bruce H. ^{[2
]}

Myers, Stephen L. ^{[2
]}

机构：

[1] Creighton Univ, Osteoporosis Res Ctr, Omaha, NE 68131 USA

[2] Eli Lilly & Co, Indianapolis, IN 46285 USA

[3] Univ Tokushima, Fuji Mem Inst Med Sci, Tokushima 770, Japan

[4] Bethesda Hlth Res, Bethesda, MD USA

[5] Lilly Res Labs Japan, Kobe, Hyogo, Japan

来源：

JOURNAL OF BONE AND MINERAL RESEARCH | 2015年 / 30卷 / 02期

关键词：

BLOSOZUMAB; SCLEROSTIN ANTIBODY; ANABOLICS; BONE MINERAL DENSITY; OSTEOPOROSIS TREATMENT; MONOCLONAL-ANTIBODY; FRACTURES; FEATURES;

D O I：

10.1002/jbmr.2351

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Sclerostin, a SOST protein secreted by osteocytes, negatively regulates formation of mineralized bone matrix and bone mass. We report the results of a randomized, double-blind, placebo-controlled multicenter phase 2 clinical trial of blosozumab, a humanized monoclonal antibody targeted against sclerostin, in postmenopausal women with low bone mineral density (BMD). Postmenopausal women with a lumbar spine T-score -2.0 to -3.5, inclusive, were randomized to subcutaneous blosozumab 180mg every 4 weeks (Q4W), 180mg every 2 weeks (Q2W), 270mg Q2W, or matching placebo for 1 year, with calcium and vitamin D. Serial measurements of spine and hip BMD and biochemical markers of bone turnover were performed. Overall, 120 women were enrolled in the study (mean age 65.8 years, mean lumbar spine T-score -2.8). Blosozumab treatment resulted in statistically significant dose-related increases in spine, femoral neck, and total hip BMD as compared with placebo. In the highest dose group, BMD increases from baseline reached 17.7% at the spine, and 6.2% at the total hip. Biochemical markers of bone formation increased rapidly during blosozumab treatment, and trended toward pretreatment levels by study end. However, bone specific alkaline phosphatase remained higher than placebo at study end in the highest-dose group. CTx, a biochemical marker of bone resorption, decreased early in blosozumab treatment to a concentration less than that of the placebo group by 2 weeks, and remained reduced throughout blosozumab treatment. Mild injection site reactions were reported more frequently with blosozumab than placebo. In conclusion, treatment of postmenopausal women with an antibody targeted against sclerostin resulted in substantial increases in spine and hip BMD. These results support further study of blosozumab as a potential anabolic therapy for osteoporosis. (c) 2014 American Society for Bone and Mineral Research.

引用

页码：216 / 224

页数：9

共 35 条

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