This slide describes briefly the controlling mechanism to balance the calcium & phosphorous levels within human serum, involving several hormones and other factors; this post carries valuable information regarding this topic and references for further readings.

1. NAME – SHUVAM SAR
M.PHARM(PHARMACOLOGY)
ADVANCED PHARMACOLOGY
ROLL – 19320219008
BENGAL SCHOOL OF TECHNOLOGY

2.  Calcium & phosphorus are present in different forms –
ionized, salt, complex salt, bound to proteins, phosphate,
etc.
 Calcium is important for – membrane transport, muscular
contractions, release of storage vesicles, and as critical
secondary messenger within cells. The main structural
component of bones & teeth.
 Phosphorus is essential component of extracellular
fluid(ECF), cell membranes, bones, teeth & most
importantly ATP, as energy currency. Mostly present in
phosphate form.[1]
 Resorption of bone, done by Osteoclast cells, involves
release of calcium & phosphate from bones’ structural
components, increases calcium & phosphorus in ECF.
 deposition of bone, done by osteoblast cells, involves
deposition of calcium & phosphorus on bones, lowering
calcium & phosphorus in ECF.
 Regulation of absorption of calcium & phosphorus in GIT
and regulation of filtration through nephrons in kidney
directly controls the calcium & phosphorus balance in the
body.[2]

3.  The balance of calcium & phosphorus in
extracellular fluid or plasma is principally
maintained by –
i. Parathyroid hormone(PTH)
ii. vitamin D &
iii. fibroblast growth factor 23 (FGF23).
 Secondary regulators are –
i. calcitonin,
ii. glucocorticoid &
iii. estrogen. [3]

4.  Secreted from parathyroid
glands located in thyroid
glands.
 When plasma calcium level
lowers, secretion of
Parathormone increases bone
resorption to increase calcium
& phosphorus level in plasma.
So, lower secretion of PTH
causes Tetany disease.
 PTH increases intestinal
absorption of calcium &
phosphorus.
 PTH decreases excretion of
calcium, but increases
excretion of Phosphorus.[4]

5.  CALCITRIOL [1,25 (OH)2D3] & 1,25
(OH)2D2 are active forms of vitamin
D.
 At high concentration, increases
bone absorption through osteoclast,
thus increasing plasma calcium
level. But low concentration,
induces bone calcification, resulting
in low plasma calcium level.
 Increases intestinal absorption of
calcium & phosphorus, plasma level
rises.
 Reduces glomerular filtration of
calcium & phosphorus, plasma level
rises.[5]

6.  It inhibits 1,25(OH) 2 D production and phosphate
reabsorption (via the sodium phosphate co-transporters
NaPi 2a and 2c) in the kidney, leading to
hypophosphatemia.
 FGF23 binds to FGF receptors 1 and 3c in the presence of
the accessory receptor Klotho.[6]

7.  Calcitonin –
i. Lowers serum calcium and phosphate by actions on bone and kidney.
ii. Calcitonin inhibits osteoclastic bone resorption.
iii. In the kidney, calcitonin reduces both calcium and phosphate
reabsorption as well as reabsorption of other ions, including sodium,
potassium, and magnesium.
iv. Ability of calcitonin to block bone resorption and lower serum calcium
makes it a useful drug for the treatment of Paget’s disease,
hypercalcemia, and osteoporosis.
 Glucocorticoid –
i. Antagonizes vitamin D-stimulated intestinal calcium transport,
ii. stimulating renal calcium excretion, and
iii. blocking bone formation. [7]
 Estrogens –
i. Estrogens can prevent accelerated bone loss during the immediate
postmenopausal period .
ii. reduce the bone-resorbing action of PTH.
iii. men who lack the estrogen receptor or who are unable to produce
estrogen because of aromatase deficiency noted marked osteopenia
and failure to close epiphyses. [8]

8. 1. Hoenderop JG, Nilius B, Bindels RJ: Calcium absorption across
epithelia, Physiol Rev 85:373, 2005
2. Berndt T, Kumar R: Novel mechanisms in the regulation of phosphorus
homeostasis, Physiology (Bethesda) 24:17, 2009.
3. Tfelt-Hanson J, Brown EM: The calcium-sensing receptor in normal
physiology and pathophysiology: A review. Crit Rev Clin Lab Sci
2005;42:35.
4. Marx SJ: Hyperparathyroid and hypoparathyroid disorders, N Engl J
Med 343:1863, 2000.
5. Pettifor JM: Rickets and vitamin D deficiency in children and
adolescents. Endocrinol Metab Clin North Am 2005;34:537.
6. Strom TM, Juppner H: PHEX, FGF23, DMP1 and beyond. Curr Opin
Nephrol Hypertens 2008;17:357.
7. Kearns AE, Khosla S, Kostenuik PJ: Receptor activator of nuclear factor
kappaB ligand and osteoprotegerin regulation of bone remodeling in
health and disease, Endocr Rev 29:155, 2008.
8. Cummings SR et al: Denosumab for prevention of fractures in
postmenopausal women with osteoporosis. N Engl J Med 2009;361:756.