Macrominerals : Calcium and phosphorus

The macrominerals include calcium (Ca²⁺), phosphorus ([P] as inorganic phosphate [P i, or PO₄³⁻]), magnesium (Mg²⁺), sodium (Na+), chloride (Cl−), and potassium (K+). [Note: The free ionic forms are electrolytes.]
Calcium and phosphorus
These macrominerals are considered together because they are components of hydroxylapatite (Ca₅[PO₄]₃OH), which makes up bones and teeth.
1. Calcium: Ca²⁺ is the most abundant mineral in the body, with ~98% being found in bones. The remainder is involved in a number of processes such as signaling, muscle contraction, and blood clotting. Ca²⁺ binds to a variety of proteins including calmodulin , phospholipase A2 , and protein kinase C  and alters their activity. [Note: Calbindin is a vitamin D–induced intracellular Ca²⁺-binding protein involved in Ca²⁺ absorption in the intestine .] Dairy products, many green vegetables (for example, broccoli, but not spinach), and fortified orange juice are good dietary sources.
Although dietary deficiency syndromes are unknown, average Ca²⁺ intake in the United States is insufficient for optimal bone health. Toxicity is seen only with supplements (tolerable upper limit [UL] = 2,500 mg/day for adults). Hypercalcemia (elevated serum Ca²⁺) can result from overproduction of parathyroid hormone (PTH). This may cause constipation and kidney stones. Hypocalcemia (low serum Ca²⁺) can result from a deficiency of PTH or vitamin D. It can lead to bone demineralization (resorption). 
Bone mass increases from infancy through the early reproductive years and then shows an age-related loss in both men and women that increases the risk for fracture. This loss is greatest in postmenopausal Caucasian women. Some studies have shown that supplementation with Ca²⁺ and vitamin D decreases this risk.
2. Phosphorus: Free phosphate (Pi) is the most abundant intracellular anion. However, 85% of the body’s phosphorus is in the form of inorganic hydroxylapatite, with most of the remainder in intracellular organic compounds such as phospholipids, nucleic acids, ATP, and creatine phosphate. Phosphate is supplied as ATP for kinases and as Pi for phosphorylases (for example, glycogen phosphorylase).
[Note: Its addition (by kinases) or removal (by phosphatases) is an important means of covalent regulation of enzymes .] Phosphorus is widely distributed in food (milk is a good source), and dietary deficiency is rare. Hypophosphatemia can be caused by refeeding carbohydrates to malnourished patients (refeeding syndrome, ), overuse of aluminum-containing antacids (aluminum chelates Pi), and increased urinary loss in response to increased production of PTH . Muscle weakness is a common symptom. Hyperphosphatemia is caused primarily by decreased PTH levels. The excess Pi can combine with Ca²⁺ and form crystals that deposit in soft tissue (metastatic calcification). [Note: The Ca²⁺/Pi ratio is important for bone formation (the ratio is ~2/1 in bone), and some experts are concerned that replacement of Ca²⁺-rich milk by Ca2+-poor, Pi-rich soft drinks can affect bone health.]
3. Hormonal regulation: Serum levels of Ca²⁺ and Pi are primarily controlled by calcitriol (1,25-dihydroxycholecalciferol, the active form of vitamin D) and PTH, both of which respond to a decrease in serum Ca²⁺.
Calcitriol, produced by the kidneys, increases serum Ca²⁺ and Pi by increasing bone resorption and intestinal absorption and renal reabsorption of Ca²⁺ and Pi (Fig. 1). PTH (from the parathyroid glands) increases serum Ca²⁺ by increasing bone resorption, increasing renal reabsorption of Ca²⁺, and activating the renal 1-hydroxylase that produces calcitriol from calcidiol  (Fig. 2). In contrast to
calcitriol, PTH decreases Pi reabsorption in the kidneys, lowering serum Pi. [Note: High serum Pi increases PTH and decreases calcitriol.] A third hormone, calcitonin (from the C cells of the thyroid gland), responds to elevated serum Ca²⁺ levels by promoting bone mineralization and increasing renal excretion of Ca²⁺ (and Pi).

Figure 2: Effect of parathyroid hormone on serum calcium (Ca²⁺). PO₄^3– =phosphate.

Figure 1:  Effect of calcitriol on serum calcium (Ca²⁺).