A randomized, double-blind phase 2 clinical trial of blosozumab, a sclerostin antibody, in postmenopausal women with low bone mineral density
Robert R. Recker,Charles Benson,Toshio Matsumoto,Michael A. Bolognese,Deborah A. Robins,Jahangir Alam,Alan Y Chiang,Leijun Hu,John H. Krege,Hideaki Sowa,Bruce H. Mitlak,Stephen L. Myers +11 more
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Treatment of postmenopausal women with an antibody targeted against sclerostin resulted in substantial increases in spine and hip BMD, and further study of blosozumab as a potential anabolic therapy for osteoporosis is supported.Abstract:
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 180 mg every 4 weeks (Q4W), 180 mg every 2 weeks (Q2W), 270 mg 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.read more
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Wnt signaling in development and tissue homeostasis.
TL;DR: An overview of Wnt-β-catenin signaling highlighting its key functions during development and adult tissue homeostasis is provided.
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Understanding the Bone in Cancer Metastasis.
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A bispecific antibody targeting sclerostin and DKK-1 promotes bone mass accrual and fracture repair
Monica Florio,Kannan Gunasekaran,Marina Stolina,Xiaodong Li,Ling Liu,Barbara Tipton,Hossein Salimi-Moosavi,Franklin J. Asuncion,Chaoyang Li,Banghua Sun,Hong Lin Tan,Li Zhang,Chun-Ya Han,Ryan Case,Amy N. Duguay,Mario Grisanti,Jennitte Stevens,James Pretorius,Efrain Pacheco,Heidi Jones,Qing Chen,Brian Soriano,Jie Wen,Brenda Heron,Frederick W. Jacobsen,Emil Brisan,William G. Richards,Hua Zhu Ke,Michael S. Ominsky +28 more
TL;DR: It is demonstrated that dual inhibition of sclerostin and DKK-1 leads to synergistic bone formation in rodents and non-human primates, and by targeting distinct facets of fracture healing, the bispecific antibody shows superior bone repair activity compared with monotherapies.
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A look behind the scenes: the risk and pathogenesis of primary osteoporosis
TL;DR: The many heritable and nonheritable factors that contribute to the pathogenesis of primary osteoporosis are discussed.
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Molecular genetics and targeted therapy of WNT-related human diseases (Review)
Masuko Katoh,Masaru Katoh +1 more
TL;DR: WNT signaling in cancer, stromal and immune cells dynamically orchestrate immune evasion and antitumor immunity in a cell context-dependent manner and WNT-targeting therapeutics have also been applied as reagents for in vitro stem-cell processing in the field of regenerative medicine.
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Population Marginal Means in the Linear Model: An Alternative to Least Squares Means
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