The application of mathematical models to reflect the organization and activity of biological systems can be viewed as a continuum of purpose. The far left of the continuum is solely the prediction of biological parameter values, wherein an understanding of the underlying biological processes is irrelevant to the purpose. At the far right of the continuum are mathematical models, the purposes of which are a precise understanding of those biological processes. No models in present use fall at either end of the continuum. Without question, however, the emphasis in regards to purpose has been on prediction, e.g., clinical trial simulation and empirical disease progression modeling. Clearly the model that ultimately incorporates a universal understanding of biological organization will also precisely predict biological events, giving the continuum the logical form of a tautology. Currently that goal lies at an immeasurable distance. Nonetheless, the motive here is to urge movement in the direction of that goal. The distance traveled toward understanding naturally depends upon the nature of the scientific question posed with respect to comprehending and/or predicting a particular disease process. A move toward mathematical models implies a move away from static empirical modeling and toward models that focus on systems biology, wherein modeling entails the systematic study of the complex pattern of organization inherent in biological systems.
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.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.