ArticleCPT: pharmacometrics & systems pharmacology2015
Connecting the Dots: Linking Osteocyte Activity and Therapeutic Modulation of Sclerostin by Extending a Multiscale Systems Model.
Article in CPT: pharmacometrics & systems pharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
What it found
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Who cites it
6 citing papers in PubMed.
- A review of mathematical modeling of bone remodeling from a systems biology perspective.Frontiers in systems biology · 2024Article
- Mathematical modeling of the effects of Wnt-10b on bone metabolism.AIChE journal. American Institute of Chemical Engineers · 2022Article
- Modeling osteoporosis to design and optimize pharmacological therapies comprising multiple drug types.eLife · 2022Article
- Validation of a quantitative systems pharmacology model of calcium homeostasis using elagolix Phase 3 clinical trial data in women with endometriosis.Clinical and translational science · 2021Article
- Pharmacometrics and systems pharmacology for metabolic bone diseases.British journal of clinical pharmacology · 2019Review
- Predictive computational modeling to define effective treatment strategies for bone metastatic prostate cancer.Scientific reports · 2016Article
Corrections and comments
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Authors and funding
4 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The goal of this work was to extend a mathematical, multiscale systems model of bone function, remodeling, and health in order to explore hypotheses related to therapeutic modulation of sclerostin and quantitatively describe purported osteocyte activity within bone remodeling events. A pharmacokinetic model with first-order absorption and dual elimination pathways was used to describe the kinetics of romosozumab, a monoclonal antibody (mAb) against sclerostin. To describe total circulating sclerostin, an extended indirect response model of inhibition of offset was developed. These models were subsequently linked to the systems model, with sclerostin signaling changes in resorption and formation through established osteocyte-mediated mechanisms. The model proposes relative contributions of the osteocyte to the RANKL pool, a major player in feedback signaling, and is used to explore hypotheses surrounding attenuation of anabolic activity after multiple doses of sclerostin mAbs, a phenomenon whose mechanism is poorly understood.
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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.