ArticleJournal of pharmacokinetics and pharmacodynamics2011
Coping with time scales in disease systems analysis: application to bone remodeling.
Article in Journal of pharmacokinetics and pharmacodynamics, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 39 citations in OpenAlex.
- Disease Systems Analysis of Bone Mineral Density and Bone Turnover Markers in Response to Alendronate, Placebo, and Washout in Postmenopausal Women.CPT: pharmacometrics & systems pharmacology · 2016Trial
- Application of a mechanism-based disease systems model for osteoporosis to clinical data.Journal of pharmacokinetics and pharmacodynamics · 2013Trial
- In silico exploration of osteoclast precursor inhibition for preventing rapid bone loss after denosumab discontinuation.NPJ systems biology and applications · 2026Article
- Mathematical modeling of bone remodeling after surgical menopause.Frontiers in systems biology · 2026Article
- A review of mathematical modeling of bone remodeling from a systems biology perspective.Frontiers in systems biology · 2024Article
- Network Pharmacology of Adaptogens in the Assessment of Their Pleiotropic Therapeutic Activity.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Modeling osteoporosis to design and optimize pharmacological therapies comprising multiple drug types.eLife · 2022Article
- Translational Quantitative Systems Pharmacology in Drug Development: from Current Landscape to Good Practices.The AAPS journal · 2019Review
- Pharmacology of bisphosphonates.British journal of clinical pharmacology · 2019Review
- QSP Toolbox: Computational Implementation of Integrated Workflow Components for Deploying Multi-Scale Mechanistic Models.The AAPS journal · 2017Article
- Understanding the Behavior of Systems Pharmacology Models Using Mathematical Analysis of Differential Equations: Prolactin Modeling as a Case Study.CPT: pharmacometrics & systems pharmacology · 2016Article
- A Six-Stage Workflow for Robust Application of Systems Pharmacology.CPT: pharmacometrics & systems pharmacology · 2016Article
- Kinetics of drug action in disease states: towards physiology-based pharmacodynamic (PBPD) models.Journal of pharmacokinetics and pharmacodynamics · 2015Article
- Modeling effects of dexamethasone on disease progression of bone mineral density in collagen-induced arthritic rats.Pharmacology research & perspectives · 2015Article
- Application of a Systems Pharmacology-Based Placebo Population Model to Analyze Long-Term Data of Postmenopausal Osteoporosis.CPT: pharmacometrics & systems pharmacology · 2015Article
- A semi-mechanistic model of bone mineral density and bone turnover based on a circular model of bone remodeling.Journal of pharmacokinetics and pharmacodynamics · 2015Article
- Sobol Sensitivity Analysis: A Tool to Guide the Development and Evaluation of Systems Pharmacology Models.CPT: pharmacometrics & systems pharmacology · 2015Article
- Integrated pharmacometrics and systems pharmacology model-based analyses to guide GnRH receptor modulator development for management of endometriosis.CPT: pharmacometrics & systems pharmacology · 2012Article
- Merging systems biology with pharmacodynamics.Science translational medicine · 2012Review
- Pharmacokinetic/pharmacodynamic modeling in inflammation.Critical reviews in biomedical engineering · 2012Review
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In this study we demonstrate the added value of mathematical model reduction for characterizing complex dynamic systems using bone remodeling as an example. We show that for the given parameter values, the mechanistic RANK-RANKL-OPG pathway model proposed by Lemaire et al. (J Theor Biol 229:293-309, 2004) can be reduced to a simpler model, which can describe the dynamics of the full Lemaire model to very good approximation. The response of both models to changes in the underlying physiology and therapeutic interventions was evaluated in four physiologically meaningful scenarios: (i) estrogen deficiency/estrogen replacement therapy, (ii) Vitamin D deficiency, (iii) ageing, and (iv) chronic glucocorticoid treatment and its cessation. It was found that on the time scale of disease progression and therapeutic intervention, the models showed negligible differences in their dynamic properties and were both suitable for characterizing the impact of estrogen deficiency and estrogen replacement therapy, Vitamin D deficiency, ageing, and chronic glucocorticoid treatment and its cessation on bone forming (osteoblasts) and bone resorbing (osteoclasts) cells. It was also demonstrated how the simpler model could help in elucidating qualitative properties of the observed dynamics, such as the absence of overshoot and rebound, and the different dynamics of onset and washout.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.