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.