Genetic disorders of calcium, phosphorus, and bone homeostasis

Abstract

Calcium and phosphorus [in the form of phosphate (H2PO4-/HPO4–2)] are the most abundant elements in the body where they subserve many functions – the most prominent of which is the formation of hydroxyapatite [Ca10(PO4)10(OH)2] – the mineral portion of bone [1, 2]. Calcium and phosphate are present in every cell in the body and are essential for normal cellular function. Calcium is indispensable for transmission of neural signals, muscle contractility, intracellular signal transduction, and secretion of cellular products. Phosphate is required for formation of nuclear and mitochondrial DNA and RNA, phospholipids for cell membrane formation, glycolysis and generation of high energy bonds (ATP), and intracellular signaling by guanosine triphosphate (GTP)-bearing proteins (G-proteins) and cyclic adenosine monophosphate (AMP). Phosphorylation of networks of intracellular proteins by many different kinases propagate the transmission of signals from the cell’s plasma membrane into the nucleus to regulate gene expression and cellular function. Genetic disorders of calcium, phosphate, and skeletal homeostasis lead to hypercalcemia, hypocalcemia, rickets or osteomalacia, osteopenia with marked skeletal fragility, and excessively dense bones.