CUED Publications database

Denosumab rapidly increases cortical bone in key locations of the femur: a 3D bone mapping study in women with osteoporosis.

Poole, KES and Treece, GM and Gee, AH and Brown, JP and McClung, MR and Wang, A and Libanati, C (2014) Denosumab rapidly increases cortical bone in key locations of the femur: a 3D bone mapping study in women with osteoporosis. J Bone Miner Res, 30. pp. 46-54.

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Abstract

Women with osteoporosis treated for 36 months with twice-yearly injections of denosumab sustained fewer hip fractures compared with placebo. Treatment might improve femoral bone at locations where fractures typically occur. To test this hypothesis, we used 3D cortical bone mapping of postmenopausal women with osteoporosis to investigate the timing and precise location of denosumab versus placebo effects in the hips. We analyzed clinical computed tomography scans from 80 female participants in FREEDOM, a randomized trial, wherein half of the study participants received subcutaneous denosumab 60 mg twice yearly and the others received placebo. Cortical 3D bone thickness maps of both hips were created from scans at baseline, 12, 24, and 36 months. Cortical mass surface density maps were also created for each visit. After registration of each bone to an average femur shape model followed by statistical parametric mapping, we visualized and quantified statistically significant treatment effects. The technique allowed us to pinpoint systematic differences between denosumab and control and to display the results on a 3D average femur model. Denosumab treatment led to an increase in femoral cortical mass surface density and thickness, already evident by the third injection (12 months). Overall, treatment with denosumab increased femoral cortical mass surface density by 5.4% over 3 years. One-third of the increase came from increasing cortical density, and two-thirds from increasing cortical thickness, relative to placebo. After 36 months, cortical mass surface density and thickness had increased by up to 12% at key locations such as the lateral femoral trochanter versus placebo. Most of the femoral cortex displayed a statistically significant relative difference by 36 months. Osteoporotic cortical bone responds rapidly to denosumab therapy, particularly in the hip trochanteric region. This mechanism may be involved in the robust decrease in hip fractures observed in denosumab-treated women at increased risk of fracture.

Item Type: Article
Uncontrolled Keywords: COMPUTATIONAL ANATOMY COMPUTED TOMOGRAPHY DENOSUMAB FEMALE FEMORAL NECK FRACTURES HIP FRACTURE OSTEOPOROSIS POSTMENOPAUSAL OSTEOPOROSIS Aged Aged, 80 and over Antibodies, Monoclonal, Humanized Bone Density Denosumab Female Femur Neck Follow-Up Studies Hip Fractures Humans Middle Aged Osteoporosis, Postmenopausal Tomography, X-Ray Computed
Subjects: UNSPECIFIED
Divisions: Div F > Machine Intelligence
Depositing User: Cron Job
Date Deposited: 17 Jul 2017 19:08
Last Modified: 22 Sep 2017 20:13
DOI: