2015 USC Gateway-McNair Scholars Program Research Presentation
1. Integrated Model for Denosumab:
Pharmacodynamics in
Postmenopausal Women
Diana Ramos, Mentor: Dr. D’Argenio
University of Southern California, USC Viterbi School of Engineering
Department of Biomedical Engineering
2015 USC Gateway/McNair Scholars Program
2. Osteoporosis
• Bone disease
• Affects 10 million Americans
• 80% are women
• Silent disease
• 43.1 million have low bone
density
Healthy Bone Osteoporosis
Figure 1
3. Specific Aims
• Implement a computational model for the model-based drug
development that might improve the evaluation of osteoporosis
therapies, leading to better treatment and prevention
• Investigate the effects of disease progression with a regimen of
different doses of Denosumab, due to the up-regulation of
RANKL on changes in bone mineral density
• Explore dose adjustments needed to compensate for the
percent decrease in bone mineral density due to changes in
RANKL
7. Conclusion
Future Work
• Exploring the effects of a deficiency in Vitamin D
and/ or estrogen levels with a linked bone
homeostasis model
• Model effectively predict changes in BMD for
postmenopausal women
• Ability to identify clinical endpoints in the treatment
of osteoporosis
• Provides a platform for testing various variables that
regulate drug response and disease progression
8. Acknowledgements
This study was supported by Dr. D’Argenio,
Professor of Biomedical Engineering at the University of
Southern California.
I would also like to thank my 2014-2015 USC
McNair/Gateway Scholar Cohort.
9. References
• Marathe, Anshu, Mark C. Peterson, and Donald E. Mager. "Integrated
Cellular Bone Homeostasis Model for Denosumab Pharmacodynamics
in Multiple Myeloma Patients." The Journal of pharmacology and
experimental therapeutics 326.2 (2008): 555-62. ProQuest. Web. 16
June 2015.
• Marathe, Dhananjay D., Anshu Marathe, and Donald E. Mager.
"Integrated Model for Denosumab and Ibandronate Pharmacodynamics
in Postmenopausal Women." Biopharmaceutics & drug disposition 32.8
(2011): 471-81. ProQuest. Web. 16 June 2015.
• Lemaire, Vincent, et al. "Modeling the Interactions between Osteoblast
and Osteoclast Activities in Bone Remodeling." Journal of theoretical
biology 229.3 (2004): 293-309. ProQuest. Web. 17 June 2015.