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

Magnesium (Mg²⁺) is crucial for several cellular and physiological processes and is tightly regulated due to health risks associated with imbalances. Mg²⁺, calcium (Ca²⁺), parathyroid hormone, and vitamin D₃ are tightly coupled, ensuring proper bone metabolism and intestinal and renal absorption of Mg²⁺ and Ca²⁺. While several Ca²⁺ homeostasis models exist, no computational model has been developed to study Mg²⁺ homeostasis. We developed a computational model of Mg²⁺ homeostasis in male rats, integrating it with an existing Ca²⁺ homeostasis model, to understand the interconnected physiological processes regulating their homeostasis. We then analyzed adaptations in these interconnected processes under (1) dietary Mg²⁺ deficiency, (2) low/high dietary Ca²⁺ with Mg²⁺ deficiency, and (3) vitamin D₃ deficiency. Model simulations predicted severe hypomagnesemia and mild hypocalcemia with significant dietary Mg²⁺ deficiency. Low dietary Ca²⁺ improved, while high dietary Ca²⁺ worsened Mg²⁺ deficiency. Finally, vitamin D₃ deficiency caused severe hypocalcemia, with minimal impact on Mg²⁺ homeostasis.