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Femoral and vertebral strength improvements in postmenopausal women with osteoporosis treated with denosumab
Keaveny, Tony M. McClung, Michael R. Genant, Harry K. Zanchetta, Jose Ruben Kendler, David Brown, Jacques P. Goemaere, Stefan Recknor, Christopher Brandi, Maria Luisa Eastell, Richard
Keaveny, Tony M.
McClung, Michael R.
Genant, Harry K.
Zanchetta, Jose Ruben
Kendler, David
Brown, Jacques P.
Goemaere, Stefan
Recknor, Christopher
Brandi, Maria Luisa
Eastell, Richard
Abstract
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.
Keywords
denosumab, hip strength, spine strength, finite element analysis, osteoporosis
Date
2014
Type
Journal article
Journal
Journal of Bone and Mineral Research
Book
Volume
29
Issue
1
Page Range
158-165
Article Number
ACU Department
Mary MacKillop Institute for Health Research
Faculty of Health Sciences
Faculty of Health Sciences
Collections
Relation URI
Source URL
Event URL
Open Access Status
Open access
License
File Access
Open