Molecular Biomarkers & Diagnosis

Calcium is involved in many physiological processes, including intracellular signalling, metabolism regulation, muscle contraction, and gene expression. The majority of calcium in the human body (up to 99%) is found in bones as calcium hydroxyapatite [Ca10(PO4)6(OH)2], with less than 1% found in extracellular fluids. The most active form of calcium in extracellular fluids is the free ionised fraction, which directly interacts with calcium channels, calcium-sensing receptors (CaSRs), and cell membranes. The gastrointestinal tract, bones, and kidneys are primarily responsible for the physiological maintenance of calcium levels. The parathyroid gland produces parathormone (PTH), which regulates calcium within narrow limits by increasing calcium absorption in the intestine, bone-calcium mobilisation, and calcium reabsorption by the kidneys. Calcium ions are thought to be the primary physiological regulators of PTH secretion through CaSRs. As a result, patients with hyperparathyroidism and hypercalcemia have lower CaSR expression in parathyroid gland tissue. However, the effect of other factors, such as L-amino acids, on CaSRs was also observed. Calcium concentration deviations above or below the normal range are now more frequently diagnosed than in the past, owing primarily to increased access to laboratory tests in developed countries. Calcium disorders are classified as hypocalcemia or hypercalcemia, and they frequently coexist with other serum biochemical abnormalities such as phosphate, alkaline phosphatase (ALP), PTH, fibroblast growth factor 23, and vitamin D levels.