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Role of parathyroid hormone,
vitamin D and calcitonin in
Bone Remodeling
Dr Agha Shafique
Department of Biochemistry
Bone Remodeling
Bone remodeling is a continuous process
of bone resorption and bone formation for
the purpose of maintaining normal bone
mass:
Bone Deposition is the apposition or
formation of new bone as a normal
physiologic process.
Bone Resorption is a process involving the
breakdown of bone by specialized cells
known as osteoclasts
CALCIUM
Calcium is the most important mineral of
the body
About 99% of calcium is present in bones
and teeth, 1% is present outside the
skeletal tissue
Calcium has wide variety of functions
Calcium cont…
Functions:
 Development of bones & teeth
 Muscle contraction
 Nerve transmission
 Blood coagulation
 Calmodulin mediated action
 Act as intracellular messenger
Parathyroid Hormone
Human PTH is a linear polypeptide that
contains 84 a.a residues.
It is synthesized as part of larger molecule
containing 115 a.a residues (pre-proPTH).
Actions of Parathyroid
Hormone
PTH act directly on bones to increase
bone resorption & mobilize Ca 2+.
In addition to increasing plasma Ca2+ ,
PTH increases phosphate excretion in
urine.
This phosphaturic action is due to a
decrease in reabsorption of phosphate in
the proximal tubules.
Actions of PTH cont…
PTH also increases reabsorption of Ca2+
in the distal tubules
PTH also increases the formation of 1,25
dihydroxy Cholecalciferol, and this
increases Ca2+ absorption from intestine
Actions of PTH cont…
On longer time scale, PTH stimulates
osteoclasts and osteoblasts with the
effect osteoclasts predominating so that
more Ca2+ is mobilized from bone.
Regulation of secretion of
PTH
Circulating ionized calcium acts directly on
the parathyroid gland in a negative
feedback fashion to regulate the secretion
of PTH.
Regulation of PTH cont…
when the plasma Ca2+ level is high ,PTH
secretion is inhibited and the Ca2+ is
deposited in bones. When it is low,
secretion is increased and Ca2+ is
mobilized from the bones .
Role of vitamin D
The active transport of Ca2+ & PO4 from
intestine is increased by metabolite of
vitamin D.
Vitamin D3 which is also called
cholecalciferol is produced in skin from 7dehydrocholesterol by action of sunlight.
Role of vitamin D cont…
In liver vitamin D3 is converted to 25hydroxycholecaciferol(25-OH D3).
It is then converted to 1,25
dihydroxycholecalciferol (calcitriol ) in the
proximal tubules of kidney.
Role of vitamin D cont…
In addition to increasing Ca2+ absorption
from the intestine, it also facilitates Ca2+
reabsorption in the kidneys.
It acts on bones, where it stimulates
calcium uptake for deposition as calcium
phosphate.
Thus calcitriol is essential for bone
formation
Role of vitamin D cont…
The formation of 1,25
dihydrocholicalciferol in the kidneys which
is catalyzed by 1alpha hydroxylase is
regulated in feed back fashion by plasma
Ca2+ & PO4.
Its formation is facilitated by PTH and
when the plasma Ca2+ level is low, PTH
secretion is increased.
Calcitonin
Human calcitonin has M.W 3500 and
contains 32 amino acid residues.
Calcitonin is not secreted until the plasma
calcium level reaches approximately
9.5mg/dl and that above this calcium level
.
Plasma calcitonin is directly proportionate
to plasma calcium .
Actions of Calcitonin
Calcitonin lowers the circulating calcium
and phosphate levels.
It exerts its calcium lowering effect by
inhibiting bone resorption.
This action is direct, and calcitonin inhibits
the activity of osteocalsts.
Rickets
It is due to deficiency of Vitamin D during
childhood. The full-blown condition in children is
characterized by weakness and bowing of
weight bearing bones, dental defects and
hypoclacemia.
Osteomalacia
– It is due to deficiency of vitamin D during
adulthood, results from demineralization of
bones, especially in women who have little
exposure to sunlight, often after several
pregnancies.
.
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