Modeling calcium and magnesium balance: Regulation by calciotropic hormones and adaptations under varying dietary intake.

Magnesium (Mg) is crucial for several cellular and physiological processes and is tightly regulated due to health risks associated with imbalances. Mg, calcium (Ca), parathyroid hormone, and vitamin D are tightly coupled, ensuring proper bone metabolism and intestinal and renal absorption of Mg and Ca. While several Ca homeostasis models exist, no computational model has been developed to study Mg homeostasis. We developed a computational model of Mg homeostasis in male rats, integrating it with an existing Ca homeostasis model, to understand the interconnected physiological processes regulating their homeostasis. We then analyzed adaptations in these interconnected processes under (1) dietary Mg deficiency, (2) low/high dietary Ca with Mg deficiency, and (3) vitamin D deficiency. Model simulations predicted severe hypomagnesemia and mild hypocalcemia with significant dietary Mg deficiency. Low dietary Ca improved, while high dietary Ca worsened Mg deficiency. Finally, vitamin D deficiency caused severe hypocalcemia, with minimal impact on Mg homeostasis.