A discrete event simulation of the adult trabecular skeleton

Abstract

A verified, but unvalidated discrete event computer simulation of the adult bone remodeling system is presented. It implements the unit-based theory of adult skeletal remodeling proposed by Frost. The simulation allows a scientist to design trials involving the adult skeleton by inputting the times of administration, and effects (remodeling cycle initiation, activity, lifespan, proliferation) on bone cells of drugs, according to his current understanding of their mechanisms of action. The simulation constantly tracks the contents and age of all bone structural units, updating each every 2.5 days, to reflect ongoing bone resorption, osteoid formation, osteoid mineralization, and the passage of time. In reality, the simulation tabulates the results of remodeling cycles which take place during the trial. The investigator may receive histomorphometric, densitometric, and biochemical data, as indicators of skeletal status, as often as every 2.5 days during the trial, far more frequently than is usually done in real experiments. At the conclusion of a trial, he may plot/review time-related graphs of the interim data. Validation trials of aging, “activation,” and clodronate administration, are presented. This simulation, when validated, could be a cost-saving device because it can increase the chance for success of any adult skeletal experiment by guiding investigators toward taking fewer, better selected measurements. Furthermore, when refined to include color graphics display of skeletal structure, it could be the basis for an educational device. This could help both the medical community and the public by providing a more ready understanding than can currently be had of adult skeletal remodeling, its relationship to adult metabolic bone disease, and the prevention/treatment of adult metabolic bone disease (e.g. osteoporosis).