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Bone Metabolism

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Introduction

Bone is a dynamic tissueits internal shape and

structure changing from moment to moment in

concert with the normal variation in mechanical

function and mineral exchange.

Has biomechanical role in locomotion

Essential for maintenance of mineral

homeostasis.

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Birds view

Molecular biology of bone

Bone mineralisation

Bone metabolism / Remodelling Bone mineral metabolism

Factors responsible for bone mass regulation

Brief overview of metabolic bone disorder.

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Molecular Biology of Bone

Bone

Bone cells Bone matrix.

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Bone Matrix

Have structural and regulating properties: help

control the cell mediated processes.

Composition depends upon age, site, dietary

history, and presence of diseases.

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Bone matrix

Inorganic phase Organic Components Water

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Inorganic Phase

70 % of matrix

Ca phosphate analogous to crystalline ca

hydroxyapatite. Ca10 (Po4)6 (OH)2.

20 to 80 nm long, 2 to 5nm thick

Small amount of impurities in the form of carbonates in

[Po4]6, Cl-, and F- replacing (OH)2.

K+, Mg++, Sr++ etc will replace Ca. These impurities alter the physical property of bone.

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Type 1 collagen

Synthesised by osteoblasts

3 polypeptide chains of 1000AA

Triple helixtwo identical alpha1 chains and one

aplha2 chain stabilised by hydrogen bonds. Linear molecule, allinged in parellel fashion with the

next molecule.

Pores present betwn the two bundles called hole

zones. Non collagenous protiens, and minerals get deposited

here.

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Osteocalcin

Syn: bone gamma carboxyglutamic acid, Gla protien.

Carboxylation converts this protien into a ca and mineral binderin matrix.

Constitutes 10 % of non collagenous protiens.

Carboxylation of this protein is Vit K dependent.

Synthesis enhanced by VitD, Inhibited by PTH, and steroids.

Excreted in non metabolised form in urine.

Can be used as marker for bone formation/ resorption diseases.

Function:

Attracts osteoclasts to the site of bone resorption

Regulates rate of mineralisation and accretion of mineral crystals.

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Osteonectin

Secreted by osteoblasts and platellets

Binds hydroxyapatite and collagen

Helps in organisation of minerals within matrixframework.

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Integrins

Osteopontin, sialoprotiens, fibronectins etc

form a part of family of cell membrane proteins

called as integrins

These integrins anchor the bone cells to matrix.

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Growth Factors

Transforming GF beta TGF B

Insulin dependent GF, IGF

IL1, 6 BMP 1-6.

All the above imp in regulating cell

differentiation, activation, growth and turnover.They are the coupling factors that link bone

formation and resorption.

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Water

Water is impregnated within the mineral crystals.

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Bone Cells

Principal Regulators of

bone metabolism

Bone cells

Osteoblasts Osteocytes Osteoclasts

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Osteoblasts

Bone forming cells

formed from osteoprogenator cell lines of mesenchymal origin

Has single polarised nuclei.

Produces matrix proteins

Alkaline phosphatase is produced and distributed in cellmembrane

There will always be a newly formed unmineralised bone matrix[osteoid] around osteoblast.

Thus its a cell that produces type 1 collagen, responsive to PTH,and produces osteocalcin when stimulated by Vit D.

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