Postmenopausal osteoporosis (PMO), leading to a higher bone fracture risk, is characterized by a significantly increasing bone porosity. Recently, denosumab, which is able to efficiently interfere with bone resorption, has been approved for the treatment of PMO. In order to optimize the design of drug administration regimes, we propose a computational methodology, based on mechanistic mathematical modeling of bone remodeling, considering the governing biochemical and biomechanical regulation mechanisms, and the targeted action of denosumab. The time-dependent serum concentration of denosumab, obtained from a pharmacokinetics model, is fed into a bone cell population model, allowing for prediction of porosity evolution in PMO patients. In order to account for the mechanobiology of bone remodeling, we utilize the concept of continuum micromechanics, which accurately provides the actual (microscopic) strain state of the investigated bone. Finally, different drug administration regimes are simulated, and their effect on the bone microarchitecture is discussed.
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ASME 2012 11th Biennial Conference on Engineering Systems Design and Analysis
July 2–4, 2012
Nantes, France
Conference Sponsors:
- International
ISBN:
978-0-7918-4487-8
PROCEEDINGS PAPER
Computer Simulation-Based Modeling of the Pharmaceutical Intervention of Postmenopausal Osteoporosis by Denosumab
Stefan Scheiner,
Stefan Scheiner
Vienna University of Technology, Vienna, Austria
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Peter Pivonka,
Peter Pivonka
The University of Western Australia, Crawley, WA, Australia
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David W. Smith,
David W. Smith
The University of Western Australia, Crawley, WA, Australia
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Colin R. Dunstan
Colin R. Dunstan
The University of Sydney, Sydney, NSW, Australia
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Stefan Scheiner
Vienna University of Technology, Vienna, Austria
Peter Pivonka
The University of Western Australia, Crawley, WA, Australia
David W. Smith
The University of Western Australia, Crawley, WA, Australia
Colin R. Dunstan
The University of Sydney, Sydney, NSW, Australia
Paper No:
ESDA2012-82990, pp. 285-289; 5 pages
Published Online:
August 12, 2013
Citation
Scheiner, S, Pivonka, P, Smith, DW, & Dunstan, CR. "Computer Simulation-Based Modeling of the Pharmaceutical Intervention of Postmenopausal Osteoporosis by Denosumab." Proceedings of the ASME 2012 11th Biennial Conference on Engineering Systems Design and Analysis. Volume 4: Advanced Manufacturing Processes; Biomedical Engineering; Multiscale Mechanics of Biological Tissues; Sciences, Engineering and Education; Multiphysics; Emerging Technologies for Inspection and Reverse Engineering; Advanced Materials and Tribology. Nantes, France. July 2–4, 2012. pp. 285-289. ASME. https://doi.org/10.1115/ESDA2012-82990
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