A Theoretical Modeling for Suggesting Unique Mechanism of Adolescent Calcium Metabolism

Abstract

Purpose: Modeling has been used for elucidating the mechanism of complex biosystems. In spite of importance and uniqueness of adolescent calcium (Ca) metabolism characterized by a threshold Ca intake, its regulatory mechanism has not been covered and even not proposed. Hence, this study aims at model-based proposing potential mechanisms regulating adolescent Ca metabolism. Methods: Two different hypothetic mechanisms were proposed. The main mechanism is conceived based on Ca-protein binding which induces renal Ca filtration, while additional mechanism assumed that active renal Ca re-absorption regulated Ca metabolism in adolescents. Mathematical models were developed to represent the proposed mechanism and simulated them whether they could produce adolescent Ca profiles in serum and urine. Results: Simulation showed that both mechanisms resulted in the unique behavior of Ca metabolism in adolescents. Based on the simulation insulin-like growth factor-1 (IGF-1) is suggested as a potential regulator because it is related to both growth, a remarkable characteristic of adolescence, and Ca metabolism including absorption and bone accretion. Then, descriptive modeling is employed to conceptualize the hypothesized mechanisms governing adolescent Ca metabolism. Conclusions: This study demonstrated that modeling is a powerful tool for elucidating an unknown mechanism by simulating potential regulatory mechanisms in adolescent Ca metabolism. It is expected that various analytic applications would be plausible in the study of biosystems, particularly with combination of experimental and modeling approaches.

A model of calcium homeostasis in the rat

“…The major objective of this study was to develop a mathematical model of calcium homeostasis in the rat so as to better understand the impact of dysfunctions (such as primary hyperparathyroidism) on calcium balance and concentration. Several models in human have been developed (24,57,69,74); however, they do not incorporate several findings that the present study seeks to account for: the role of the renal CaSR, the delayed response of vitamin D 3 synthesis to changes in PTH levels, and the rapidly exchangeable pool in bone [with the exception, for the latter, of the model of Peterson and Riggs (69)]. …”