A physiologically based mathematical model of integrated calcium homeostasis and bone remodeling
Abstract
Bone biology is physiologically complex and intimately linked to calcium homeostasis. The literature provides a wealth of qualitative and/or quantitative descriptions of cellular mechanisms, bone dynamics, associated organ dynamics, related disease sequela, and results of therapeutic interventions. We present a physiologically based mathematical model of integrated calcium homeostasis and bone biology constructed from literature data. The model includes relevant cellular aspects with major controlling mechanisms for bone remodeling and calcium homeostasis and appropriately describes a broad range of clinical and therapeutic conditions. These include changes in plasma parathyroid hormone (PTH), calcitriol, calcium and phosphate (PO4), and bone-remodeling markers as manifested by hypoparathyroidism and hyperparathyroidism, renal insufficiency, daily PTH 1-34 administration, and receptor activator of NF-kappaB ligand (RANKL) inhibition. This model highlights the utility of systems approaches to physiologic modeling in the bone field. The presented bone and calcium homeostasis model provides an integrated mathematical construct to conduct hypothesis testing of influential system aspects, to visualize elements of this complex endocrine system, and to continue to build upon iteratively with the results of ongoing scientific research.
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The literature search excluded many relevant publications that do not include "systems" or "QSP" in their title and highly impactful models published elsewhere.
“As a caveat, this excludes many relevant publications that do not include “systems” or “QSP” in their title10, 11 and highly impactful models published elsewhere.12”
From Reproducibility of Quantitative Systems Pharmacology Models: Current Challenges and Future Opportunities (2019) · cites this paper as [12]
In the 2013 filing of recombinant human parathyroid hormone (rhPTH) for the treatment of hypoparathyroidism, FDA reviewers used a publicly available calcium homeostasis QSP model to explore alternative dosage regimens.
“The US Food and Drug Administration (FDA) reviewers raised some concerns about the hypercalciuria being observed in the clinical study and used a publicly available calcium homeostasis QSP model12 to explore alternative dosage regimens.”
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- Authors
- Peterson, M. C., & Riggs, M. M.
- Affiliations
- Amgen (United States) (US)
- Metrum Research Group (United States) (US)
- Corresponding author
- Peterson, Mark C.
- ORCID
- Riggs, Matthew M.
- Venue
- Bone
- Publisher
- Elsevier BV
- Published
- 2010-01
- Volume
- 46
- Issue
- 1
- Pages
- 49-63
- ISSN
- 1873-2763 (ISSN-L)
- 8756-3282
- OpenAlex
- W2127955916
- Cited by
- 198
- References
- 77
- Citations by year
- 2026: 5 · 2025: 9 · 2024: 11 · 2023: 6 · 2022: 12 · 2021: 14 · 2020: 14 · 2019: 19 · 2018: 14 · 2017: 15 · 2016: 20 · 2015: 11 · 2014: 11 · 2013: 7 · 2012: 12
- FWCI
- 4.01
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Bone (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Health Sciences › Medicine › Nephrology › Parathyroid Disorders and Treatments
- Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
- Keywords
- calcium homeostasis, bone remodeling, parathyroid hormone, 1,25-dihydroxyvitamin D3, hypoparathyroidism, hyperparathyroidism, renal failure, teriparatide, RANKL inhibition, phosphate, bone turnover markers
- MeSH terms
- Calcitriol, Calcium, Models, Biological, Models, Theoretical, Parathyroid Hormone, Phosphates, Bone Remodeling
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