Denosumab for prevention of fractures in postmenopausal women with osteoporosis.

Details

Serval ID
serval:BIB_1A80E7E12300
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Denosumab for prevention of fractures in postmenopausal women with osteoporosis.
Journal
New England Journal of Medicine
Author(s)
Cummings S.R., San Martin J., McClung M.R., Siris E.S., Eastell R., Reid I.R., Delmas P., Zoog H.B., Austin M., Wang A., Kutilek S., Adami S., Zanchetta J., Libanati C., Siddhanti S., Christiansen C., FREEDOM Trial
Contributor(s)
FREEDOM Trial, Cummings S., Christiansen C., Delmas P., Eastell R., McClung M., Reid I., Siris E., Aqua K., Lee E., Boling E., Bolognese M., Burch F., Cohen S., Fiske D., Petit C., Pierson M., Garrison K., Gallup E., Geisberg H., Hassman D., Helfrich D., Krohn K., Cuevas E., Larson W., Seiler J., Lederman S., Lewiecki M., MacCarter D., McClung M., Miller P., Moffett A.<Suffix>Jr</Suffix> , Recknor C., Simon J., Trapp R., Woodson G.<Suffix>3rd</Suffix> , Bone H., Murtaugh T., Ruckle J., Wasnich R., Gallagher C., Dhillon G., Feldman R., Pennington G., Saxe P., Goldberg C., Rogers K., Keller M., Swor M., Rosen A., Stjernholm M., Adachi J., Brown J., Faraawi R., Kendler D., Kremer R., Olszynski W., Yuen CK., McKendry R., Boudreau J., Man Z., Zanchetta J., Mautalen C., de Gregorio L., Eis S., Radominski S., da Silva N., Griz L., Provenza J., Zerbini C., García-Hernández P., Araujo-Arias M., Bueno E., Fuentes-Cantu A., Perez M., Balderas-Acata J., Avila-Armengol H., de la Peña-Rodríguez M., Nicholson G., Ebeling P., Sambrook P., Hooper M., Prins J., Russell A., Reid I., Gilchrist N., Preisinger E., Resch H., Fahrleitner-Pammer A., Huber J., Kudlacek S., Reginster JY., Kaufman JM., Boonen S., Body JJ., Devogelaer JP., Tegibjearg C., Juel R., Alexandersen P., Hoeck HC., Jensen JE., Välimäki M., Salmi J., Delmas P., Fardellone P., Weryha G., Benhamou CL., Maugars Y., Roux C., Stahl HD., Blome-Henning U., Lochman B., Kopsch U., Roitenberg A., Adami S., Brandi M., Minisola S., Bianchi G., Sinigaglia L., Frediani B., Marcolongo R., Fiore C., Nuti R., Realdi G., Dijkmans B., Laan R., Bruyn G., Deijl A., Meesters E., Lems W., Verhage A., van de Walle V., Halse J., Hoiseth A., Syversen U., Stakkestad J., Minguella J., Mola E., Torres M., Gómez J., Hawkins F., Román J., Alvaro-Gracia J., Del Pino J., Palacios S., Ljunggren O., Toss G., Samsioe G., Mellström D., Löfgren J., Törring O., Lippuner K., Krieg MA., Uebelhart D., Eastell R., Thomas H., Shaw H., Donnachie H., Pavel-Knox I., Robinson J., Kola N., Sarmiento R., Pawa R., Savani N., Kucerova I., Kuba V., Vyskocil V., Kutilek S., Novosad P., Slesinger J., Dokoupilova E., Doubravsky J., Gorgol J., Pavelka K., Valter I., Maasalu K., Kull I., Phenekos C., Lyritis G., Dimitriadis A., Spengler B., Insperger A., Balázs T., Lakatos P., Takács K., Szombati I., Tarján K., Valkusz Z., Torma O., Seregely K., Kaze I., Lejnieks A., Medne A., Tamulaitiene M., Velickiene D., Stonkus S., Brincat M., Walecki J., Bykowska M., Sidorowicz-Bialynicka A., Szechinski J., Korkosz M., Supronik J., Koziara M., Czerwinski E., Milewicz A., Jeka S., Kania G., Gidzinski P., Sawicki A., Tlustochowicz W., Franek E., Hoszowski K., Pluskiewicz W., Porawska W., Zgliczynski W., Killinger Z., Masaryk P., Kmecova Z., Tomkova S., Spustova V., Steno B., Zbranca E., Codreanu C., Hristov V., Russev T., Ivanova AM., Velev R., Mitkov M., Troev D., Brankovic S., Dimic A., Pilipovic N., Hlatky M., Goldschlager N., Herrington D., Ryan C., Migliorati C., Ruggiero S., Schubert M.
ISSN
1533-4406 (Electronic)
ISSN-L
0028-4793
Publication state
Published
Issued date
11/2009
Volume
361
Number
8
Pages
756-765
Language
english
Notes
Publication types: Journal Article ; Multicenter Study ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
BACKGROUND: Denosumab is a fully human monoclonal antibody to the receptor activator of nuclear factor-kappaB ligand (RANKL) that blocks its binding to RANK, inhibiting the development and activity of osteoclasts, decreasing bone resorption, and increasing bone density. Given its unique actions, denosumab may be useful in the treatment of osteoporosis.
METHODS: We enrolled 7868 women between the ages of 60 and 90 years who had a bone mineral density T score of less than -2.5 but not less than -4.0 at the lumbar spine or total hip. Subjects were randomly assigned to receive either 60 mg of denosumab or placebo subcutaneously every 6 months for 36 months. The primary end point was new vertebral fracture. Secondary end points included nonvertebral and hip fractures.
RESULTS: As compared with placebo, denosumab reduced the risk of new radiographic vertebral fracture, with a cumulative incidence of 2.3% in the denosumab group, versus 7.2% in the placebo group (risk ratio, 0.32; 95% confidence interval [CI], 0.26 to 0.41; P<0.001)--a relative decrease of 68%. Denosumab reduced the risk of hip fracture, with a cumulative incidence of 0.7% in the denosumab group, versus 1.2% in the placebo group (hazard ratio, 0.60; 95% CI, 0.37 to 0.97; P=0.04)--a relative decrease of 40%. Denosumab also reduced the risk of nonvertebral fracture, with a cumulative incidence of 6.5% in the denosumab group, versus 8.0% in the placebo group (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01)--a relative decrease of 20%. There was no increase in the risk of cancer, infection, cardiovascular disease, delayed fracture healing, or hypocalcemia, and there were no cases of osteonecrosis of the jaw and no adverse reactions to the injection of denosumab.
CONCLUSIONS: Denosumab given subcutaneously twice yearly for 36 months was associated with a reduction in the risk of vertebral, nonvertebral, and hip fractures in women with osteoporosis. (ClinicalTrials.gov number, NCT00089791.)
Keywords
Aged, Aged, 80 and over, Antibodies, Monoclonal/adverse effects, Antibodies, Monoclonal/pharmacology, Antibodies, Monoclonal, Humanized, Bone Density/drug effects, Bone Density Conservation Agents/adverse effects, Bone Density Conservation Agents/pharmacology, Bone Remodeling/drug effects, Female, Fractures, Bone/epidemiology, Fractures, Bone/prevention & control, Hip Fractures/epidemiology, Hip Fractures/prevention & control, Humans, Incidence, Middle Aged, Osteoporosis, Postmenopausal/drug therapy, RANK Ligand/adverse effects, RANK Ligand/pharmacology, Risk, Spinal Fractures/epidemiology, Spinal Fractures/prevention & control
Pubmed
Web of science
Create date
12/01/2010 16:57
Last modification date
20/08/2019 12:51
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