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. 2022 Jul 12:10:901720.
doi: 10.3389/fbioe.2022.901720. eCollection 2022.

Clinical Data for Parametrization of In Silico Bone Models Incorporating Cell-Cytokine Dynamics: A Systematic Review of Literature

Charles Ledoux  1 , Daniele Boaretti  1 , Akanksha Sachan  1   2 , Ralph Müller  1 , Caitlyn J Collins  1   3
Affiliations

Clinical Data for Parametrization of In Silico Bone Models Incorporating Cell-Cytokine Dynamics: A Systematic Review of Literature

Charles Ledoux et al. Front Bioeng Biotechnol. .

Abstract

In silico simulations aim to provide fast, inexpensive, and ethical alternatives to years of costly experimentation on animals and humans for studying bone remodeling, its deregulation during osteoporosis and the effect of therapeutics. Within the varied spectrum of in silico modeling techniques, bone cell population dynamics and agent-based multiphysics simulations have recently emerged as useful tools to simulate the effect of specific signaling pathways. In these models, parameters for cell and cytokine behavior are set based on experimental values found in literature; however, their use is currently limited by the lack of clinical in vivo data on cell numbers and their behavior as well as cytokine concentrations, diffusion, decay and reaction rates. Further, the settings used for these parameters vary across research groups, prohibiting effective cross-comparisons. This review summarizes and evaluates the clinical trial literature that can serve as input or validation for in silico models of bone remodeling incorporating cells and cytokine dynamics in post-menopausal women in treatment, and control scenarios. The GRADE system was used to determine the level of confidence in the reported data, and areas lacking in reported measures such as binding site occupancy, reaction rates and cell proliferation, differentiation and apoptosis rates were highlighted as targets for further research. We propose a consensus for the range of values that can be used for the cell and cytokine settings related to the RANKL-RANK-OPG, TGF-β and sclerostin pathways and a Levels of Evidence-based method to estimate parameters missing from clinical trial literature.

Keywords: agent - based modeling; aging; bone; cell population dynamics; cytokine; osteoporosis; parametrization approach; verification and validation.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
PRISMA diagram illustrating the effect of each inclusion/exclusion criterion.
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