Physiology of Bone.pptx

8/11/2019 Physiology of Bone.pptx

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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 vitalorgans, provides an environment for

marrow (both blood forming and fat

storage), acts as a mineral reservoir

for calcium homeostasis and areservoir of growth factors and

cytokines, and also takes part in

acid – base 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 depositedwithin the matrix. During life, the bones undergo

processes of longitudinal and radial growth,

modeling (reshaping), and remodeling .



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 themonocytemacrophage lineage (hematopoietic stem

cells that give rise to monocytes and macrophages) .

Mononuclear monocytemacrophage precursor cells

have been identified in various tissues, but bonemarrow monocytemacrophage 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 includeproteoglycans, sialoproteins, glacontainingproteins, and 2HS-glycoprotein

BONE MINERALS

Crystalline hydroxyapatite [Ca10(PO 4)6(OH)2] isthe chief mineral component of bone, constitutingapproximately about a quarter of the volume andhalf of the mass of normal adult bone



Bone Formation

Ossification (or osteogenesis) is the process offormation 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 ofresorption 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 boneformation).

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 theparathyroid 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 inthe kidney/increase

reabsorbtion of Ca2+

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 Ca2+ in

matrix bone



Calcitonin Role

Calcitonin is synthesizedand secreted by the

parafollicular cells of the

thyroid gland

Calcitonin acts todecrease plasma Ca2+ levels.

While PTH and vitamin Dact to increase plasmaCa2+-- only calcitonincauses a decrease inplasma Ca2+.



The target cell for calcitonin is the osteoclast. Calcitonin acts via increased cAMP

concentrations to inhibit osteoclast motility andcell shape and inactivates them.

The major effect of calcitonin administration is arapid fall in Ca2+ caused by inhibition of boneresorption.



Vitamin D

Vitamin D is a lipid soluble hormone that binds toa 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



Abnormalities Of Bone Mineral

Metabolism

Abnormalities of bone remodeling can produce avariety of skeletal disorder.

a. Osteoporosis

b. Hyperparathyroidism and Hyperthyroidism

c. Paget’s 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



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