BONE METABOLISM by Group V

BONE
Bone is a highly specialized
supporting framework of the body,
characterized by its rigidity,
hardness, and power of regeneration
and repair. It protects the vital
organs, provides an environment for
marrow (both blood forming and fat
storage), acts as a mineral reservoir
for calcium homeostasis and a
reservoir of growth factors and
cytokines, and also takes part in
acidbase balance (Taichman 2005
Physiology of Bone Formation
Bone is composed of support cells, namely,
osteoblasts and osteocytes; remodeling cells,
namely, osteoclasts; and non-mineral matrix of
Collagen and noncollagenous proteins called
osteoid, with inorganic mineral salts deposited
within the matrix. During life, the bones undergo
processes of longitudinal and radial growth,
modeling (reshaping), and remodeling .


osteoblas
Osteoblasts originate from
mesenchymal stem cells
(osteoprogenitor cells) of
the bone marrow stroma
and are responsible for
bone matrix synthesis and
its subsequen
mineralization.
Osteoblast are and
deposition
mononucleated, and their
shape varies
Osteoblast are
responsible for regulation
of osteoclast and
deposition of bone matrix

Osteocytes
steoclasts are the only cells that are known to be
capable of resorbing bone. They are typically
multinucleated. Osteoclasts are derived from
mononuclear precursor cells of the
monocytemacrophage lineage (hematopoietic stem
cells that give rise to monocytes and macrophages) .
Mononuclear monocytemacrophage precursor cells
have been identified in various tissues, but bone
marrow monocyte- macrophage precursor cells are
thought to give rise to most osteoclasts.
Bone Matrix
The structure of bone is constituted by:
(a) Inorganic (69 %) component, consisting of
hydroxyapatite (99 %)
(b) Organic (22 %), constituted by collagen (90 %)
and noncollagen structural proteins which include
proteoglycans, sialoproteins, glacontaining
proteins, and 2HS-glycoprotein
BONE MINERALS
Crystalline hydroxyapatite [Ca10(PO 4)6(OH)2] is
the chief mineral component of bone, constituting
approximately about a quarter of the volume and
half of the mass of normal adult bone


Bone Formation
Ossification (or osteogenesis) is the process of
formation of new bone by cells called osteoblasts.
Three basic steps involved in osteogenesis are:
(a) Synthesis of extracellular organic matrix
(osteoid)
(b) Matrix mineralization leading to the formation of
bone
(c) Remodeling of bone by the process of
resorption and reformation


Bone
Remodeling
Bone remodeling is a lifelong process wherein
old bone is removed from the skeleton (a sub-
process called bone resorption), and new bone is
added (a sub-process called ossification or bone
formation).
Mediator of Remodeling
a. Osteoclast
b. Osteoblast
c. RANK




Remodeling Phases
PARATIROID HORMONE (PTH)
PTH is synthesized
and secreted by the
parathyroid gland
The Chief Cells in the
parathyroid gland are
the principal site of
PTH synthesis.
It is THE MAJOR of
Ca homeostasis in
humans.

PTH has three major
effects:
1) PTH directly stimulates
bone resorption;
2) PTH directly stimulates
recovery of calcium in
the kidney/increase
reabsorbtion of Ca
2+
3) PTH stimulates the
production of 1a,25-
dihydroxy-Vitamin D
from its precursors.
Moleculer Mechanism of PTH
PTH1 RECEPTOR
AT OSTEOBLAST
CELL MEMBRAN
Increase Ca
2+
in
matrix bone

Calcitonin Role
Calcitonin is synthesized
and secreted by the
parafollicular cells of the
thyroid gland

Calcitonin acts to
decrease plasma Ca
2+

levels.

While PTH and vitamin D
act to increase plasma
Ca
2+
-- only calcitonin
causes a decrease in
plasma Ca
2+
.

The target cell for calcitonin is the osteoclast.
Calcitonin acts via increased cAMP
concentrations to inhibit osteoclast motility and
cell shape and inactivates them.
The major effect of calcitonin administration is a
rapid fall in Ca
2+
caused by inhibition of bone
resorption.

Vitamin D
Vitamin D is a lipid soluble hormone that binds to
a typical nuclear receptor, analogous to steroid
hormones.
Because it is lipid soluble, it travels in the blood
bound to hydroxylated a-globulin.
PTH stimulates vitamin D synthesis ---- PTH
stimulates 1a-hydroxylase
Vitamin D Syntetize
VITAMIN D ACTION
The main action of 1,25-(OH)
2
-D is to stimulate
absorption of Ca
2+
from the intestine
Vitamin D acts via steroid hormone like receptor
to increase transcriptional and translational
activity
One gene product is calcium-binding protein
(CaBP)
CaBP facilitates calcium uptake by intestinal cells

Vitamin D Actions on Bones
Another important target for 1,25-(OH)
2
-D is the bone.
Osteoblasts, but not osteoclasts have vitamin D
receptors.
1,25-(OH)
2
-D acts on osteoblasts which produce a
paracrine signal that activates osteoclasts to resorb Ca
++

from the bone matrix.
1,25-(OH)
2
-D also stimulates osteocytic osteolysis.

Abnormalities Of Bone Mineral
Metabolism
Abnormalities of bone remodeling can produce a
variety of skeletal disorder.
a. Osteoporosis
b. Hyperparathyroidism and Hyperthyroidism
c. Pagets Disease
d. Osteomalacia/Rickets
e. Osteopetrosis

Osteoporosis
Osteoporosis is a very
common metabolic
disorder of the skeleton,
where in the bone mineral
density (BMD) is reduced,
the bone microarchi-
tecture is disrupted
Osteoporosis may be:
Primary
(postmenopausal/senile)
Secondary cause
(nutrition, endocrine, drug,
malignancy, chronic
disease, idiopathic) (Raisz
1997 )

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