Comparison of the Effect of Denosumab and Alendronate on BMD and Biochemical Markers of Bone Turnover in Postmenopausal Women With Low Bone Mass: A Randomized,Blinded, Phase 3 Trial |
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| Authors: | Jacques P Brown Richard L Prince Chad Deal Robert R Recker Douglas P Kiel Luiz H de Gregorio Peyman Hadji Lorenz C Hofbauer Jose M Álvaro‐Gracia Huei Wang Matthew Austin Rachel B Wagman Richard Newmark Cesar Libanati Javier San Martin Henry G Bone |
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| Institution: | 1. Laval University and Le Centre Hospitalier Universitaire de Québec, Quebec City, Québec, Canada;2. Dr Brown is an investigator for Amgen and has served as a consultant for and/or received honoraria or research funding from Abbott, Amgen Arthrolab, Bristol Myers Squibb, Eli Lilly, Genizon, GlaxoSmithKline, Merck Frosst, Nicox, Novartis, Pfizer, Procter & Gamble, Roche, Sanofi‐Aventis, Servier, Roche, Wyeth, and Zelos. Dr Prince is an investigator for Amgen and has received honoraria or research funding and/or served as a consultant for Eli Lilly, Merck, Novartis, and Servier. Dr Deal has served as a consultant for, on the speakers bureau of, and/or received research funding or consulting fees from Amgen, Eli Lilly, GlaxoSmithKline, Novartis, and Procter & Gamble. Dr Recker is an investisultant for, on the speakers bureau of, and/or received research funding or consulting fees from Amgen, Eli Lilly, GlaxoSmithKline, Novartis, and Procter & Gamble. Dr Recker is an investigator for Amgen and has served as a consultant for and/or received honoraria from Allelix, Amgen, Eli Lilly, GlaxoSmithKline, Merck, Novartis, NPS, Procter & Gamble, Roche, and Wyeth. Dr Kiel has received honoraria and/or research funding from Amgen, Hologic, Merck, Novartis, and Pfizer and has served as a consultant or on the speakers bureau for Amgen, Eli Lilly, GSK, Merck, Novartis, Procter & Gamble, Roche, and Wyeth. Dr Alvaro‐Gracia is an investigator for Amgen. Dr de Gregorio has received research grants from Amgen, Merck, and Roche. Dr Hadji is an investigator for Amgen. Dr Hofbauer is an investigator for Amgen. Drs Wang, Austin, Wagman, Newmark, Cesar Libanati, and Javier San Martin are employees and shareholders of Amgen. Dr Bone is an investigator for Amgen, Eli Lilly, Merck, Novartis, Pfizer, and Zelos;3. has served as a consultant for Amgen, Merck, Nordic Bioscience, Osteologix, Pfizer, and Zelos;4. and has received speaker honoraria from Merck and Novartis.;5. Sir Charles Gairdner Hospital, University of Western Australia, Perth, Australia;6. Cleveland Clinic, Cleveland, Ohio, USA;7. Creighton University, Omaha, Nebraska, USA;8. Institute for Aging Research, Hebrew SeniorLife and Harvard Medical School, Boston, Massachusetts, USA;9. SYNARC/CCBR, Rio de Janeiro, Brazil;10. Philipps‐University of Marburg, Marburg, Germany;11. Department of Medicine III, Technical University, Dresden, Germany;12. Hospital de la Princesa, Madrid, Spain;13. Amgen, Thousand Oaks, California, USA;14. Amgen, San Francisco, California, USA;15. Stanford University School of Medicine, Stanford, California, USA;16. Michigan Bone and Mineral Clinic, Detroit, Michigan, USA |
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| Abstract: | Denosumab is a fully human monoclonal antibody that inhibits bone resorption by neutralizing RANKL, a key mediator of osteoclast formation, function, and survival. This phase 3, multicenter, double‐blind study compared the efficacy and safety of denosumab with alendronate in postmenopausal women with low bone mass. One thousand one hundred eighty‐nine postmenopausal women with a T‐score ≤ ?2.0 at the lumbar spine or total hip were randomized 1:1 to receive subcutaneous denosumab injections (60 mg every 6 mo Q6M]) plus oral placebo weekly (n = 594) or oral alendronate weekly (70 mg) plus subcutaneous placebo injections Q6M (n = 595). Changes in BMD were assessed at the total hip, femoral neck, trochanter, lumbar spine, and one‐third radius at 6 and 12 mo and in bone turnover markers at months 1, 3, 6, 9, and 12. Safety was evaluated by monitoring adverse events and laboratory values. At the total hip, denosumab significantly increased BMD compared with alendronate at month 12 (3.5% versus 2.6%; p < 0.0001). Furthermore, significantly greater increases in BMD were observed with denosumab treatment at all measured skeletal sites (12‐mo treatment difference: 0.6%, femoral neck; 1.0%, trochanter; 1.1%, lumbar spine; 0.6%, one‐third radius; p ≤ 0.0002 all sites). Denosumab treatment led to significantly greater reduction of bone turnover markers compared with alendronate therapy. Adverse events and laboratory values were similar for denosumab‐ and alendronate‐treated subjects. Denosumab showed significantly larger gains in BMD and greater reduction in bone turnover markers compared with alendronate. The overall safety profile was similar for both treatments. |
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| Keywords: | BMD denosumab alendronate postmenopausal osteoporosis biochemical markers of bone turnover |
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