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Femoral and Vertebral Strength Improvements in Postmenopausal Women With Osteoporosis Treated With Denosumab

In the randomized, placebo-controlled FREEDOM study of women aged 60 to 90 years with postmenopausal osteoporosis, treatment with denosumab once every 6 months for 36 months significantly reduced hip and new vertebral fracture risk by 40% and 68%, respectively. To gain further insight into this effi...

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Autores principales: Keaveny, Tony M, McClung, Michael R, Genant, Harry K, Zanchetta, Jose R, Kendler, David, Brown, Jacques P, Goemaere, Stefan, Recknor, Chris, Brandi, Maria L, Eastell, Richard, Kopperdahl, David L, Engelke, Klaus, Fuerst, Thomas, Radcliffe, Hoi-Shen, Libanati, Cesar
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BlackWell Publishing Ltd 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4238810/
https://www.ncbi.nlm.nih.gov/pubmed/23794225
http://dx.doi.org/10.1002/jbmr.2024
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author Keaveny, Tony M
McClung, Michael R
Genant, Harry K
Zanchetta, Jose R
Kendler, David
Brown, Jacques P
Goemaere, Stefan
Recknor, Chris
Brandi, Maria L
Eastell, Richard
Kopperdahl, David L
Engelke, Klaus
Fuerst, Thomas
Radcliffe, Hoi-Shen
Libanati, Cesar
author_facet Keaveny, Tony M
McClung, Michael R
Genant, Harry K
Zanchetta, Jose R
Kendler, David
Brown, Jacques P
Goemaere, Stefan
Recknor, Chris
Brandi, Maria L
Eastell, Richard
Kopperdahl, David L
Engelke, Klaus
Fuerst, Thomas
Radcliffe, Hoi-Shen
Libanati, Cesar
author_sort Keaveny, Tony M
collection PubMed
description In the randomized, placebo-controlled FREEDOM study of women aged 60 to 90 years with postmenopausal osteoporosis, treatment with denosumab once every 6 months for 36 months significantly reduced hip and new vertebral fracture risk by 40% and 68%, respectively. To gain further insight into this efficacy, we performed a nonlinear finite element analysis (FEA) of hip and spine quantitative computed tomography (QCT) scans to estimate hip and spine strength in a subset of FREEDOM subjects (n = 48 placebo; n = 51 denosumab) at baseline, 12, 24, and 36 months. We found that, compared with baseline, the finite element estimates of hip strength increased from 12 months (5.3%; p < 0.0001) and through 36 months (8.6%; p < 0.0001) in the denosumab group. For the placebo group, hip strength did not change at 12 months and decreased at 36 months (–5.6%; p < 0.0001). Similar changes were observed at the spine: strength increased by 18.2% at 36 months for the denosumab group (p < 0.0001) and decreased by –4.2% for the placebo group (p = 0.002). At 36 months, hip and spine strength increased for the denosumab group compared with the placebo group by 14.3% (p < 0.0001) and 22.4% (p < 0.0001), respectively. Further analysis of the finite element models indicated that strength associated with the trabecular bone was lost at the hip and spine in the placebo group, whereas strength associated with both the trabecular and cortical bone improved in the denosumab group. In conclusion, treatment with denosumab increased hip and spine strength as estimated by FEA of QCT scans compared with both baseline and placebo owing to positive treatment effects in both the trabecular and cortical bone compartments. These findings provide insight into the mechanism by which denosumab reduces fracture risk for postmenopausal women with osteoporosis.
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spelling pubmed-42388102014-11-28 Femoral and Vertebral Strength Improvements in Postmenopausal Women With Osteoporosis Treated With Denosumab Keaveny, Tony M McClung, Michael R Genant, Harry K Zanchetta, Jose R Kendler, David Brown, Jacques P Goemaere, Stefan Recknor, Chris Brandi, Maria L Eastell, Richard Kopperdahl, David L Engelke, Klaus Fuerst, Thomas Radcliffe, Hoi-Shen Libanati, Cesar J Bone Miner Res Original Articles In the randomized, placebo-controlled FREEDOM study of women aged 60 to 90 years with postmenopausal osteoporosis, treatment with denosumab once every 6 months for 36 months significantly reduced hip and new vertebral fracture risk by 40% and 68%, respectively. To gain further insight into this efficacy, we performed a nonlinear finite element analysis (FEA) of hip and spine quantitative computed tomography (QCT) scans to estimate hip and spine strength in a subset of FREEDOM subjects (n = 48 placebo; n = 51 denosumab) at baseline, 12, 24, and 36 months. We found that, compared with baseline, the finite element estimates of hip strength increased from 12 months (5.3%; p < 0.0001) and through 36 months (8.6%; p < 0.0001) in the denosumab group. For the placebo group, hip strength did not change at 12 months and decreased at 36 months (–5.6%; p < 0.0001). Similar changes were observed at the spine: strength increased by 18.2% at 36 months for the denosumab group (p < 0.0001) and decreased by –4.2% for the placebo group (p = 0.002). At 36 months, hip and spine strength increased for the denosumab group compared with the placebo group by 14.3% (p < 0.0001) and 22.4% (p < 0.0001), respectively. Further analysis of the finite element models indicated that strength associated with the trabecular bone was lost at the hip and spine in the placebo group, whereas strength associated with both the trabecular and cortical bone improved in the denosumab group. In conclusion, treatment with denosumab increased hip and spine strength as estimated by FEA of QCT scans compared with both baseline and placebo owing to positive treatment effects in both the trabecular and cortical bone compartments. These findings provide insight into the mechanism by which denosumab reduces fracture risk for postmenopausal women with osteoporosis. BlackWell Publishing Ltd 2014-01 2013-12-19 /pmc/articles/PMC4238810/ /pubmed/23794225 http://dx.doi.org/10.1002/jbmr.2024 Text en © 2014 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals, Inc. on behalf of the American Society for Bone and Mineral Research. http://creativecommons.org/licenses/by-nc-nd/3.0/ This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
spellingShingle Original Articles
Keaveny, Tony M
McClung, Michael R
Genant, Harry K
Zanchetta, Jose R
Kendler, David
Brown, Jacques P
Goemaere, Stefan
Recknor, Chris
Brandi, Maria L
Eastell, Richard
Kopperdahl, David L
Engelke, Klaus
Fuerst, Thomas
Radcliffe, Hoi-Shen
Libanati, Cesar
Femoral and Vertebral Strength Improvements in Postmenopausal Women With Osteoporosis Treated With Denosumab
title Femoral and Vertebral Strength Improvements in Postmenopausal Women With Osteoporosis Treated With Denosumab
title_full Femoral and Vertebral Strength Improvements in Postmenopausal Women With Osteoporosis Treated With Denosumab
title_fullStr Femoral and Vertebral Strength Improvements in Postmenopausal Women With Osteoporosis Treated With Denosumab
title_full_unstemmed Femoral and Vertebral Strength Improvements in Postmenopausal Women With Osteoporosis Treated With Denosumab
title_short Femoral and Vertebral Strength Improvements in Postmenopausal Women With Osteoporosis Treated With Denosumab
title_sort femoral and vertebral strength improvements in postmenopausal women with osteoporosis treated with denosumab
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4238810/
https://www.ncbi.nlm.nih.gov/pubmed/23794225
http://dx.doi.org/10.1002/jbmr.2024
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