Clinical_Rounds_in_Endocrinology_Volume_II_-_Pediatric_Endocrinology

138

7. What are the regulators of calcium homeostasis?

Intracellular calcium is 10,000 times lower than serum ionized calcium, and

normal levels of both serum and intracellular calcium are required for neuro-

muscular excitability and cardiac contractility. Therefore, minute-to-minute

regulation of serum calcium is essential for maintenance of these vital func-

tions. Normal levels of serum calcium are maintained by coordinated action of

parathyroid hormone (PTH), 1,25(OH) 2 D, and possibly, FGF-23 and calcito-

nin. PTH is the prime regulator of serum calcium, and the circulating level of

calcium in turn regulates PTH secretion by acting through calcium-sensing

receptors (CaSR) present in the parathyroid gland. PTH directly promotes bone

resorption, increases renal reabsorption of calcium in distal convoluted tubule

(DCT), and facilitates intestinal calcium absorption by stimulation of renal

1 α-hydroxylase activity in proximal convoluted tubule (PCT). Serum calcium

also regulates its own excretion independent of PTH by acting through cal-

cium-sensing receptor present in thick ascending limb of loop of Henle (TALH)

in the kidney. FGF-23 inhibits 1α-hydroxylase activity and possibly suppresses

PTH secretion. The role of calcitonin in calcium homeostasis is uncertain in

humans; however, it inhibits bone resorption and increases calcium excretion.

Further, these hormones also maintain the steep gradient between extracellular

and intracellular calcium levels by regulation of the activity of calcium exchange

pumps present on cell membranes (Fig. 5.4).

Intramembranous

bone formation

Mesenchymal

stem cells

Chondroblasts

Endochondral

bone formation

Osteoblasts

Fig. 5.3 Types of bone formation

5 Rickets–Osteomalacia