Bone Health

Quantitative Systems Pharmacology Modeling of X-linked Hypophosphatemia Disease Pathway Normalization to Predict the Impact of Burosumab Treatment on Serum Biomarkers in Adult and Pediatric Patients

Presented at ACoP 2024. The Bone Health QSP model was extended by incorporating XLH disease mechanisms and burosumab impact on serum phosphate and other biomarkers using clinical data from adult and pediatric patients with XLH. The model reproduced clinically observed changes in pharmacodynamic markers in both adult and pediatric patients with XLH; normalization of serum phosphate with burosumab treatment was successfully replicated, facilitating a better understanding of burosumab dosing in patients with XLH going forward. The model could potentially be used to optimize treatment in the clinical setting.

Development and evaluation of a predictive model of hyperphosphatemia induced by inhibition of FGFR by extending an existing multiscale systems pharmacology

Matthew M. Riggs, Howard A. Ball, Kanji Komatsu, Akihiro Yamada.  Poster presented at 2020 American Conference on Pharmacometrics (ACoP11) virtual meeting. 10 November 2020.

Model code and supporting material is available here.

Model-based Dose Selection for a GnRH Receptor Antagonist in Endometriosis and Uterine Fibroids (UF) to Reduce Symptoms While Preventing Lumbar Spine Bone Mineral Density (BMD) Loss (slide deck)

Presentation by Kyle Baron, PharmD, Ph.D., at the American Conference of Pharmacometrics in October 2019. Poster can be found here.
Authors: Kyle Baron, Oliver Pohl, Matthew Riggs, Jonathan French, Jean-Pierre Gotteland, Ramon Garcia

Model-based Dose Selection for a GnRH Receptor Antagonist in Endometriosis and Uterine Fibroids (UF) to Reduce Symptoms While Preventing Lumbar Spine Bone Mineral Density (BMD) Loss (poster)

Poster presented at the American Conference of Pharmacometrics in October 2019. Accompanying slides can be found here.
Authors: Kyle Baron, Oliver Pohl, Matthew Riggs, Jonathan French, Jean-Pierre Gotteland, Ramon Garcia

Open-Source and Open-Science to Progress the Integration of Pharmacometrics and Systems Pharmacology

Riggs, Matthew. Presentation at ISoPNE iPSP event. Cambridge, MA. 26 Aug 2019.

Pharmacometrics and systems pharmacology for metabolic bone diseases

Riggs MM, Cremers S. British Pharmacological Society. 85(6):1136–46. 28 January 2019. https://doi.org/10.1111/bcp.13881

When learn/confirm leads to expand/understand: The expanding role of quantitative systems pharmacology in the betterment of therapeutics development

Riggs MM. Clin Pharmacol Ther. 98:394. 18 December 2018. doi: 10.1002/cpt.1287

Multiscale physiology-based modeling of mineral bone disorder in patients with chronic kidney disease and secondary hyperparathyroidism on hemodialysis: application to etelcalcetide treatment effects on calcium homeostasis

Riggs MM. Poster presented at 2018 American Conference on Pharmacometrics (ACoP9). San Diego, CA. 9 Oct 2018. Abstract #T-078.

Evaluations of scale: lessons learned while developing and extending a mineral and bone health multiscale systems pharmacology model

Riggs MM. Presentation at 2018 American Conference on Pharmacometrics (ACoP9). San Diego, CA. 9 Oct 2018.

Multi-scale iPSP model of physiologically-based representations to describe bone mineral homeostasis and interrelated effects

Riggs MM. Presentation at 2018 American Conference on Pharmacometrics (ACoP9). San Diego, CA. 8 Oct 2018.

A model of fracture risk used to examine the link between bone mineral density and the impact of different therapeutic mechanisms on fracture outcomes in patients with osteoporosis

Eudy-Byrne RJ, Gillespie W, Riggs MM. Gastonguay MR. J Pharmacokinet Pharmacodyn (2017).  First online 28 Oct 2017. https://doi.org/10.1007/s10928-017-9551-z

Systems pharmacology model development to provide physiologically based interpretation and drug development decision support in osteoporosis and other bone mineral-related diseases

Riggs, M.  Presented at Pharmacology 2016, annual meeting of the British Pharmacological Society, London, December 2016.

Extension of multi-scale systems pharmacology model to evaluate effect of vitamin D3 pharmacokinetics on bone health

Ocampo-Pelland AS, Gastonguay MR, Riggs MM.  Presented at the 7th American Conference on Pharmacometrics (ACoP), Bellevue, WA; October 2016.

A mathematical model to quantify links between bone mineral density, patient factors and therapeutic interventions on fracture risk in patients with osteoporosis

Eudy-Byrne RJ, Gillespie WR, Riggs MM, Gastonguay MR.  Poster presented at: American Society for Bone and Mineral Research Annual Meeting; September 2016.

Model-based meta-analysis for development of a population-pharmacokinetic (PPK) model for Vitamin D3 and its 25OHD3 metabolite using both individual and arm-level data

Ocampo-Pelland AS, Gastonguay MR, French JF, Riggs MM.  J Pharmacokinet Pharmacodyn. 2016 Apr;43(2):191-206.

Connecting the dots: Linking osteocyte activity and therapeutic modulation of sclerostin by extending a multiscale systems model

Eudy RJ, Gastonguay MR, Baron KT, and Riggs MM.  CPT: Pharmacometrics & Systems Pharmacology. 2015;4(9):527-536. doi:10.1002/psp4.12013.

Extensions of a multiscale systems pharmacology model of bone mineral balance and its regulation of bone health

Riggs MM. Presented at Sunrise Session: Integration of Systems Modeling in Clinical Development: Successes, Challenges, and Future Outlook at the American American Society for Clinical Pharmacology and Therapeutics Annual Meeting, 2013.

Systems pharmacology model development to provide physiologically-based interpretation and drug development decision support in osteoporosis and other bone-related diseases

Riggs M.  Presented at the Annual Meeting of the American Society for Clinical Pharmacology and Therapeutics, 2013.

An evaluation of calcilytic effects on parathyroid hormone and bone mineral density response using a physiologically-based, multiscale systems pharmacology model

Kyle T. Baron, Matthew M. Riggs, Ryoko Sawamura, Takako Shimizu, Fumihiko Okada, Jin Zhou, Takahiro Shibayama, Mendel Jansen. Presented at the American Society of Bone and Mineral Research (ASBMR), October, 2013.

Predicting nonlinear changes in bone mineral density over time using a multiscale systems pharmacology model

Peterson MC and Riggs MM. CPT Pharmacometrics Syst Pharmacol. 2012 Nov; 1(11): e14. Published online 2012 Nov 14. doi: 10.1038/psp.2012.15

Qualification of a physiologically-based model for predicted bone marker and bone mineral density changes associated with denosumab treatment

Riggs MM, Baron KT, Plan EL, Gastonguay MR. Presented at American Society of Bone Mineral Research (ASBMR) Annual Meeting, Minneapolis, MN; October 14, 2012 (Abstract SU0363).

Bayesian joint modeling of bone mineral density and repeated time-to-fracture event for multiscale bone systems model extension

Plan EL, Baron KT, Gastonguay MR, French JL, Gillespie WR, and Riggs MM. Presented at the 21st Annual Meeting of the Population Approach Group Europe (PAGE), Venice, Italy, 2012, Abstract 2592.

Systematic extension of a physiologic model of bone and calcium homeostasis

Riggs MM. . Presented at the AAPS Biotechnology Conference, San Diego, CA; May 22, 2012.

Multiscale physiology-based modeling of mineral bone disorder in patients with impaired kidney function

Riggs MM, Peterson MC, Gastonguay MR. The Journal of Clinical Pharmacology. 52(1 Suppl):45S-53S. January 2012. doi:10.1177/0091270011412967

 

Applying a multiscale physiologic system model to evaluate bone-related disease and therapeutic responses

Riggs MM. Presented at First Indiana Clinical and Translational Sciences Institute (CTSI) Symposium on Disease and Therapeutic Response Modeling. Indiana University – Purdue University Indianapolis; Indianapolis, IN; 13 November 2011.

A physiologically-based, multi-scale, mathematical model of integrated calcium homeostasis and bone remodeling

Riggs MM. Presented at ACOP; April 2011; San Diego, CA.

A physiologically-based, multiscale model used to predict progressive bone mineral density loss due to chronic renal disease

Riggs MM, Gastonguay MR, Peterson MC. Presented at 2010 American Association of Pharmaceutical Scientists (AAPS) Annual Meeting, New Orleans LA; 17 November 2010; Poster # W4403

Extension of a multiscale model of calcium homeostasis and bone remodeling to include the progressive effects of estrogen loss during menopause transition

Riggs MM, Gillespie WR, Gastonguay MR, Peterson MC. Presented at National Institute of General Medical Sciences Quantitative Systems Pharmacology Workshop II. Bethesda, MD; 9 September 2010.

A physiologically based mathematical model of integrated calcium homeostasis and bone remodeling

Peterson MC, Riggs MM. Bone. 46: 49-63. January 2010.