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CONTENTS
• Introduction
• Functions of bone
• Division of skeletal system
• Classification of bone
• Structural anatomy of long bones
• Composition of bone
• Bone development
INDIAN DENTAL ACADEMY
Leader in continuing Dental Education
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INTRODUCTION
Bone or osseous tissue represents the highest differentiation
among supporting tissues. It is rigid tissue that constitutes most of
the skeleton of higher vertebrates.
Skeleton : Bony and cartilaginous framework of the body
constitutes the skeleton.
Endoskeleton : Where the skeleton is located internally on the
body. In human anatomy, the term skeleton usually means
endoskeleton.
Exoskeleton : In some vertebrates, the skeletal framework is
found both externally (exoskeleton) and internally (endoskeleton).
In human beings the exoskeleton is very rudimentary, being
represented by nails and enamel of teeth only.
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Bone, in common with other connective tissues,
consists of cells, fibres and ground substance, but unlike the
others, its extra cellular components are calcified, making it
a hard, unyielding substance ideally suited for its supportive
and protective function in the skeleton.
The alveolar process is the bone that forms and
supports the tooth sockets (alveoli). It forms when the tooth
erupts in order to provide the osseous attachments to the
forming periodontal ligament, it disappears gradually when
the tooth is lost.
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1. Support : The skeleton provides a framework for the body,
and as such, it supports soft tissues and provides a point of
attachment for many muscles.
2. Protection : Many internal organs are protected from injury
by the skeleton. For example, the brain is protected by the
cranial bones, the spinal cord by the vertebrae, the heart and
lungs by the rib cage, and internal reproductive organs by the
pelvic bones.
3. Movement facilitation : Bones serve as levers to which
muscles are attached. When the muscles contract, bones
acting as levers and movable joints acting as fulcrums
produce movement.
4. Mineral Storage : Bones store several minerals that can be
distributed to other parts of the body upon demand. The
principal stored minerals are calcium and phosphorus.www.indiandentalacademy.com
5. Storage of blood cell-producing cells: Red marrow in certain
bones is capable of producing blood cells, a process called
hematopoiesis (hem-a-to-poy-E-sis) or hemopoiesis. Red
marrow consists of blood cells in immature stages, fat cells,
and macrophages. Red marrow produces red blood cells,
some white blood cells, and platelets.
6. Storage of energy : Lipids stored in cells of yellow marrow
are an important source of chemical energy.
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DIVISIONS OF THE SKELETAL SYSTEM
REGIONS OF THE SKELETON NUMBER OF BONES
AXIAL SKELETON
Skull
Cranium 8
Face 14
Hyoid 1
Auditery ossicles (3 in each ear) 6
Vertebral column 26
Thorax
Sternum 1
Ribs 24
80
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APPENDICULAR SKELETON
Pectoral (shoulder) girdles
Clavicle 2
Scapula 2
Upper extremities
Humerus 2
Ulna 2
Radius 2
Carpals 16
Metacarpals 10
Phalanges 28
Pelvic (hip) girdle
Coxal, Pelvic or hip bone 2
Lower extremities
Femur 2
Fibula 2
Tibia 2
Patella 2
Tarsals 14
Metatarsals 10
Phalanges 28
126
Total = 206www.indiandentalacademy.com
CRANIAL BONES
a. Frontal Bone 1
b. Parietal Bone 2
c. Temporal Bone 2
d. Occipital Bone 1
e. Sphenoid Bone 1
f. Ethmoid Bone 1
ab
c
d
e
f
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FACIAL BONES
Nasal Bone 2
Maxillae 2
Zygomatic Bones 2
Mandible 1
Lacrimal Bones 2
Palatine Bones 2
Inferior Nasal Conchae 2
Vomer 1
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CLASSIFICATION OF BONES
A. According to Position
1. Axial : Bones forming the axis of the body, e.g., skull,
ribs, sternum and vertebrae.
2. Appendicular : Bones forming the skeleton of limbs
(appendages of the body).
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B. According to Size and Shape
1. Long Bones : present in upper and lower limbs.
Possess three parts : (i) upper end (ii) shaft (iii) lower end.
The two ends are usually expanded for forming articulations and giving
attachments to muscles and ligaments. The shaft is tubular with a central
medullary cavity.
Examples : Humerus, radius, ulna, femur, tibia and fibula.
Long bones act as levers for movements and locomotion.
2. Short long bones : Same as above but are miniature in size.
The length of bone exceeds other measurements.
Examples : Metacarpals, metatarsals and phalanges.
3. Short Bones : Small, polyhedral and generally cuboidal in shape. Examples :
Carpal and tarsal bones. Short bones provide strength and compactness but
range of movement is limited.
4. Flat Bones : Expanded and plate like. They protect vital structure and provide
extensive areas for muscular attachment. Examples : Scapula, sternum, ribs,
parietal and frontal bones. www.indiandentalacademy.com
5. Irregular bones : Irregular in general outline and do not fit in
any of the above categories. Examples : Vertebrae, some skull
bones.
6. Pneumatic bones : Flat or irregular bones possessing a hollow
space within their body which contains air. Presence of air filled
spaces provide economical methods of expansion of bones in size
and make them lighter. Examples : Ethmoid, maxilla, mastoid part
of temporal bone.
7. Sesamoid bones : Sesamoid means “seed like”. They are nodules
of bone which develop in certain tendons and do not possess
periosteum and Haversian systems. They ossify after birth. They
diminish friction, modify and may also change the direction of the
pull of muscle. Examples : Pisiform, patella (which is the largest
sesamoid bone and develops in quadriceps femoris tendon).
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C. According to Gross Structure
1. Compact (Lamellar) Bone : the outer cortical part of long bones,
which is hard and has a homogeneous appearance.
2.Spongy (cancellous) Bone : The inner part of bone which is
less hard and presents a spongy appearance.
Examples :Flat, Short and Irregular Bones and ends of long
bones.
3.Diploic Bone : Consists of inner and outer tables of compact
bone with an intervening porous layer which is occupied by a
spongy substance consisting of bone marrow and diploic veins
e.g., most of cranial bones.
D. According to Development
Embroyonic mesenchymatous tissue is the precursor of a bone, further
development occurs by two methods.
1. Membranous (Ectochondral) bones : Which develop in
membrane.
2. Cartilaginous (Endochondral) bones : Which develop in
cartilage.
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Structural Anatomy of Long Bone
1. Diaphysis ( dia = through; physis = growth). The shaft
or long, main portion of the bone.
2. Epiphyses (epi=above: physis = growth). The
extremities or ends of the bone (singular is epiphysis).
3. Metaphysis (me-TAF-I-sis). The region in a mature
bone where the diaphysis joins the epiphysis. In a growing
bone, it is the region including the epiphyseal plate
where cartilage is reinforced and then replaced by bone.
4. Articular cartilage : A thin layer of hyaline cartilage
covering the epiphysis where the bone forms a joint
with another bone. The cartilage reduces friction
and absorbs shock at freely movable joints.
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5. Periosteum : (peri= around;osteo= bone) A dense, white, fibrous
covering around the surface of the bone not covered by articular
cartilage. The periosteum consists of two layers. The outer fibrous
layer is composed of connective tissue containing blood vessels,
lymphatic vessels, and nerves that pass into the bone. The inner
osteogenic layer contains elastic fibers, blood vessels, osteoprogenitor
cells, osteoclasts, and osteoblasts. The periosteum is essential for bone
growth, repair, and nutrition. It also serves as a point of attachment for
ligaments and tendons.
6. Medullary or marrow cavity. The space within the diaphysis that
contains the fatty yellow marrow in adults. Yellow marrow consists
primarily of fat cells and a few scattered blood cells. Thus, yellow
marrow functions in fat storage.
7. Endosteum. A layer of osteoprogenitor cells and osteoblasts that
lines and medullary cavity and also contains scattered osteoclasts (cells
that assume a role in the removal of bone).
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Bone is not completely solid. In fact, all bone has some
spaces between its hard components. The spaces provide channels
for blood vessels that supply bone cells with nutrients. The spaces
also make bones lighter. Depending on the size and distribution of
the spaces, the regions of a bone may be categorized as compact or
spongy.
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The layer of compact bone is
thicker in the diaphysis than the
epiphyses. Compact bone tissue
provides protection and support and
helps the long bones resist the stress of
weight placed on them.
One main difference is that
adult compact bone has a concentric ring
structure, whereas spongy bone does not.
Blood vessels and nerves from the
periosteum penetrate the compact bone
through perforating (volkmann’s)
canals. The blood vessels of these canals connect with blood vessels and nerves
of the medullary cavity and those of the central (Haversian) canals. The central
canals run longitudinally through the bone. Around the canals are concentric
lamellae rings of hard, calcified, intercellular substance. Between the lamellae are
small spaces called lacunae. Which contain osteocytes, Osteocytes, as noted
earlier, are mature osteoblasts that no longer produce new bone tissue and
function to support daily cellular activities of bone tissue.
COMPACT BONE
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Radiating in all directions
from the lacunae are minute canals
called canaliculi. The canaliculi
connect with those of other lacunae
and, eventually, with the central
canals. An intricate network is
formed throughout the bone.
Provides numerous routes so that
nutrients can reach the osteocytes
and wastes can be removed. Each
central canal, with its surrounding
lamellae, lacunae, osteocytes and
canaliculi, is called an osteon
(Haversian system). The areas
between osteons contain
interstitial lamellae.
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SPONGY BONE
Spongy bone does not contain true osteons. It consists of an
irregular latticework of thin plates of bone called Trabeculae. The
spaces between the trabeculae of some bones are filled with red
marrow. The cells of red marrow are responsible for producing blood
cells. Within the trabeculae lie lacunae, which contain osteocytes.
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COMPOSITION OF BONE
Cells of Bone
- Osteoprogenitor cells
- Osteoblast cells.
- Osteocytes
- Osteoclast cells.
Organic part – 33% - 35%
Collagen – 88% - 90% (Type – I)
Non collagen – 10% - 11%.
Glycoproteins – 6% - 9% (Mono, di, poly and oligosaccharides).
Proteoglycanes – 0.8% (sulfated and Non sulfated)
Sialoproteins – 0.35%
Lipids – 0.4%
Inorganic Part – 65% - 67%
- Calcium & Phosphates – 95%
(Hydroxyapatite Crystals – Ca10
(Po4
)6
(OH)2
)
- Magnesium
- Trace elements – Nickel, Iron, Fluoride, Cadmium, Magnesium, Zinc and
Molybdenum.
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Osteoblasts
Osteoblasts are uninucleated
cells that synthesized both
collagenous and noncollagenous
bone protein. They are responsible
for mineralization and are derived
from a multipotent mesenchymal
cell. Osteoblasts have all the
characteristics of hard tissue
forming cells. They constitute a
cellular layer over the forming bone
surface. When bone is no longer
forming, the surface osteoblasts
become inactive and are termed
lining cells(bone maintenance)
Osteoblasts exhibit high levels
of alkaline phosphate on the outer
surface of their plasma
membranes,this distinguishes the
ostioblast from the fibroblast
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Other enzymes that
participate in there activity are
ATPase and pyrophosphates.
Osteoblasts secrete, in addition to
type I and type V collagen and small
amounts of several noncollagenous
proteins, a variety of cytokines.
Osteoblasts under the
stimulation of interleukin 6 also
produce their own hydrolytic
enzymes that aid in destroying or
modifying the unmineralized matrix.
Thus freeing the osteoblast from its
own secreted matrix. The hormones
most important in bone metabolism
are parathyroid hormone. 1,25
dihydroxyvitamin D, calcitonin,
estrogen, and the
glucocorticoids,which have a
influence on osteoblasts. www.indiandentalacademy.com
As osteoblasts secrete bone
matrix, some of them become
entrapped in lacunae and are then
called osteocytes. The number of
osteoblasts that become osteocytes
varies depending on the rapidity of
bone formation. The more rapid the
formation, a more osteocytes are
present per unit volume. As a
general rule, embryonic bone and
repair bone have more osteocytes
than does lamellar bone.
Osteocyte
Osteocytes gradually lose most of their matrix synthesizing machinery and
become reduced in size. The space in the matrix occupied by an osteocyte is called
the osteocytic lacuna. Narrow extensions of these or canaliculi, that form radiating
osteocytic processes maintain contact with adjacent osteocytes and osteoblasts the
endosteum, periosteum, and Haversian canals.
Failure of any part of this inter connecting system result in hyper
mineralization (sclerosis) and death of the bone.www.indiandentalacademy.com
Osteoclast
Compared to all other bone cells and their precursors, the
multinucleated osteoclast is a much larger cell. Because of their size, be
identified under the light microscopy, generally seen in a cluster rather than
singly. The osteoclast is characterized by acid phosphatase within its
cytoplasmic vesicles and vacuoles, which distinguishes it from other giant cells
and macrophages.
Typically osteoclasts are found against the bone surface occupying
shallow, hollowed out depressions, called Howship’s lacunae.
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Adjacent to the tissue surface, their cell membrane is thrown into a
myriad of deep folds that form a brush border. This clear or “sealing” zone
attached the cells to the mineralized surface. Isolates a micro environment
between them and the bone surface. The cell organelles consist of many
nuclei, each surrounded by multiple Golgi complexes, an array of mitochondria
and free polysomes, a rough endoplasmic reticulum, many coated transport
vesicles, and numerous vacuolar structures. Osteoblast are also rich in
lysosomal enzymes.
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Thus the sequence of resorptive events is considered to be
1. Attachment of osteoclasts to the mineralized surface of bone.
2. Creation of a sealed acidic environment through action of the proton pump,
which demineralizes bone and exposes the organic matrix.
3. Degradation of this exposed organic matrix to its constituent amino acids
by the action of released enzymes.
4. Uptake of mineral ions and amino acids by the cell.
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Organic part – 33% - 35%
Collagen – 88% - 90% (Type – I)
Non collagen – 10% - 11%.
Glycoproteins – 6% - 9% (Mono, di, poly and
oligosaccharides).
Proteoglycanes – 0.8% (sulfated and Non sulfated)
Sialoproteins – 0.35%
Lipids – 0.4%
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Collagen forms a highly
ordered system of collagen fibers
with the typical axial periodicity of
640 A° to 700 A° and a unique
protein composition of about one
third glycine residues, one fifth
amino acid residues, a large number
of alanine residues and very few
aromatic amino acids, Cysteine in
completely lacking.
A single collagen fibril is a
three standard coil composed of
three adjacent left handed helixes
(designated collagen polymers al,
al, a2) bound together by
intromolecular cross linkage and
twisted about a common axis.
COLLAGEN
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When newly synthesized (Young )
collagen is denatured, it separates into two
al chains and one a2 chain, each with a
molecular weight of about 100,000. Other
collagen gives rise to two double and one
triple chain (B11, B12, and Y112) whose
molecular weights are 200,000 and 300,000
respectively.
Although the composition of bone
collagen is similar to other types of
collagen, it is insoluble in solvents used to
extract collagens from other tissues (neutral
salt solutions and weak organic acids). This
characteristic is thought to be due to the
presence of strong intermolecular bonds
between and along the length of adjacent
macromolecules. www.indiandentalacademy.com
PROTEINPOLYSACCHARIDES
Proteinpolysaccharides (PPS) comprise 4% to 5% of the organic
constituents of bone. They are compounds consisting of a polypeptide
chain to which side chains of highly sulfated polysaccharides are
covalently bound. The principal polysaccharides of bone of chondroitin-4
sulfate (Chondroitin sulfate A). Its role is not clear, but it appears to inhibit
mineralization of bone by strongly completing with Ca2+
ions.
In certain diseases (eg.: the mucopolysaccharidoses) increased
urinary excretion of polysaccharides takes place. The loss of
polysaccharides form bone and cartilage results in specific skeletal
deformities.
Noncollagenous protein amounts to about 0.5% of the organic
constituents, but most of this fraction represents the protein core of PPS.
LIPIDS
Less than 0.4% of the organic constituents of bone is composed of
lipids, consisting of triglycerides, free fatty acids, phospholipids and
cholesterol. www.indiandentalacademy.com
INORGANIC CONSTITUTENTS
The dry weight of bone is composed of 65% to 67%
inorganic mineral, 95% of which is a calcium and phosphate solid.
An “amorphous” Ca-P solid is present in greater amounts in young
newly formed tissue (40% to 50%) than in older, more mature
bone (25% to 30%).
Only about 0.65% of human bone calcium is part of a
readily exchangeable pool. The sites where rapid exchange takes
place can be identified by radionuclides and appear to be the lining
of the haversian canals and resorption cavities.
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CALCIUM
Calcium salts are relatively insoluble, especially as phosphates and
carbonates. The secondary form of calcium phosphate, CaHPO4
has
solubility of greater than 10-3
M and the ions of this form circulate in the
ECF at approximately half this concentration.
Calcium is complexed by many organic compounds, particularly
proteins. This characteristics is essential to strengthening and regulating the
permeability of the cell membrane. For the normal functioning of cells, intra
cellular Ca2+
ion concentration must be maintained in the range of 10 –7 M.
A normal PH must be maintained and concentrations of Ca2+ and HPO4
ions must not exceed the range of 10 –3 M to avoid calcium phosphate
precipitation within the cell.
The calcium ion, when absorbed by the intestinal mucosa, or during
renal tubular resorption after glomerular filtration, must be transported
though the cell itself and pumped out of the cell with sufficient rapidity to
avoid disturbing the cellular processes. Calcium concentration in plasma is
approximately 10 mg / dl.
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The dominant role in the maintenance of calcium homestasis is
played by the constant resorption and deposition of bone minerals
throughout life. To a lesser degree, other internal factors such as hormonal
Parathyroid hormone (PTH), calcitonin (renal tubular resorption) and
vitamin D metabolites exert roles that help to maintain constant plasma
calcium concentrations.
The surface of
active bone tissue are
covered by a layer of cells
that form a dynamic
interface between the fluid
in contact with the inter
cellular components of
bone and the
ECF.Calcium ions in
bone, intestine and kidney
are transported though the
cell toward the ECF. The source of ions in the gut is the dietary intake;
ions transported through the renal tubule are derived from the glomerular
filtrate.
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Intestinal absorption depends on dietary sources plus factors that
influences this absorption (eg. Vitamin D metabolites), bile salts to emulsify
the fats (to facilitate fat-soluble vitamin D absorption), PTH and calcitonin.
In the absence of adequate oral intake, the renal tubular absorption
approaches 100%, whereas the bone surface returns more than 100%.
VITAMIN D (CHOLECALCIFEROL)
Angus and coworkers isolated vitamin D in 1931 and named it as
calciferol. The production of vitamin D in the skin is directly proportional to
the exposure to sunlight and inversely proportional to the pigmentation of
skin. Melanin is a natural sunscreen. The cholecalciferol is first transported to
liver, where hydroxylation occurs, to form 25 hydroxy cholecalciferol and is
the major transport form. In the kidney, it is further hydroxylated at the 1st
position forming 1,25-dihydroxy cholecalciferol, also called Calcitriol, the
active form of the vitamin. www.indiandentalacademy.com
Effects:
a) Intestinal villi cells
b) Bone osteoblasts
c) Distal tubular cells of
Kidney
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Vitamin D and Intestinal Absorption of Calcium:
Calcitriol promotes the absorption of calcium and phosphorus from the
intestine. In the brush-border surface, calcium is absorbed passively. From
the intestinal cell to blood, absorption of calcium needs energy. It is either by
the sodium-calcium exchange mechanism or calcium-calbindin complex.
Calcitriol acts like a steroid hormone. It enters the target cell and binds to a
cytoplasmic receptor, Calbindin. Due to the increased availability of calcium
binding protein, the absorption of calcium is increased.
Effect of Vitamin D in Bone:
Mineralisation of the bone is increased by increasing the activity of
osteoblasts. It produces the differentiation of osteoclast precursors from
multinucleated cells of osteoblast lineage. Calcitriol stimulates osteoblasts
which secrete alkaline phosphatase. Due to this enzyme, the local
concentration of phosphate is increased. The ionic product of calcium and
phosphorus increases, leading to mineralisation.
Effect of Vitamin D in Renal Tubules:
Calcitriol increases the reabsorption of calcium and phosphorus by renal
tubules, therefore both minerals are conserved.
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PARATHYROID HORMONE (PTH):
Ivar Sandstrom discovered the parathyroid glands in 1880. In 1926,
Collip isolated the PTH. This hormone is secreted by the four parathyroid
glands embedded in the thyroid tissue. The chief cells of the gland secrete
the PTH. Storage of PTH is only for about one hour. Control of release of
the hormone is by negative feedback by the ionized calcium in serum.
Normal PTH level in serum is 10-60 ng/L. The PTH has three major
independent sites of action; bone, kidney and intestines. All the three actions
of PTH increase serum calcium level.
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In the bone PTH causes
demineralization or decalcification. It
induces pyrophosphatase in the
osteoclasts. The numbers of osteoclasts
are also increased (release lactate).
PTH also causes secretion of
collagenase from osteoclasts. This
causes loss of matrix and bone
resorption.
In Kidney PTH causes decreased renal
excretion of calcium and increased
excretion of phosphates. The action is
mainly through increase in reabsorption
of calcium from kidney tubules.
PTH stimulates 1-
hydroxylation of 25 hydroxycalciferol
in kidney to produce calcitriol. This
from intestine. indirectly increases calcium absorptionwww.indiandentalacademy.com
Calcitonin:
Hirsch isolated it in 1962.
It is secreted by the thyroid
parafollicular or clear cells.
Calcitonin secretion is stimulated
by serum calcium.
Calcitonin decreases serum
calcium level. It inhibits
resorption of bone. It decreases
the activity of osteoclasts and
increases that of osteoblasts.
Calcitonin together promote the
bone growth and remodeling. In
kidney, calcitonin increases
phosphorus excretion through
urine; this action is similar to
PTH. www.indiandentalacademy.com
Vitamin D PTH Calcitonin
Blood calcium Increased Drastically
increased
Decreased
Main action Absorption from
gut
Demineralisation Opposes
demineralization
Calcium
absorption from
gut
Increased Increased
(Indirect)
Bone resorption Decreased Increased Decreased
Deficiency
manifestation
Rickets Tetany
Use in rickets Drug of choice Contra indicated Theoretically
beneficial
Effect of excess Hypercalcemia+ Hypercalcemia+ + Hypocalcemia
Comparison of action of three major factors affecting serum
calcium
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PHOSPHORUS
Phosphorus exists as a completely ionized inorganic phosphate in the
bloodstream. Eighty percent of the mineral in the body resides in the
skeleton, where it is combined with calcium as a complete hydroxyapatite,
the formula for which is approximately Ca10
(PO4
)6
(OH)2
. Phosphate in bone
consists of a labile fraction, which is in equilibrium with the phosphate ions
in the blood stream and stable fraction, which is fixed in the skeleton.
The minimum daily requirements in the normal adult is 0.88 g and is
slightly more for growing children and pregnant women. The main food
source of phosphorus is milk, with smaller amounts obtained form meat,
cheese, eggs, nuts and whole cereal. While flour and rice have a small
content. Phosphorus exists in food in both organic and inorganic forms.
Absorption takes place from the small intestine in the form of soluble
inorganic phosphate.
An excess of ingested calcium encourages the precipitation of
insoluble phosphates within the intestinal lumen, thereby lessening the
absorption of phosphate. As an result the serum phosphate level is lowered,
leading to hypophosphatemic rickets or osteomalacia.
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When ingested calcium is inadequate, a relative excess of serum
phosphates exists. Serum calcium levels must be stored chiefly by
compensatory hyperparathyroidism, which causes bone resorption, increases
phosphate urinary excretion and decreases its tubular resorption.
The normal level of serum phosphate as ionized inorganic
phosphate is 3mmg to 4mg/dl in the adult and 5mg to 6 mg/dl in the infant.
Excretion takes place principally in the urine as monosodium (acid)
or disodium (alkaline) phosphates and in lesser amounts as a salt of
potassium, ammonium, calcium and magnesium. Ninety percent of excreted
phosphate is in the inorganic form.
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The urinary excretion of phosphate mainly depends on dietary
intake, which must be carefully controlled for several days before
determinations can be made of intake output, serum levels and renal
tubular resoption rates. The normal range of urinary excretion for adults
is 340mg to 840mg /day, whereas that for children is 530mg to 840
mg/day. Values above or below these levels are considered abnormal.
Calcium inhibits bone resorption, thereby lowering the serum
phosphate level, which in turn reduces the amount of phosphate excreted
by the kidneys. Calcitonin also directly inhibits tubular resorption of
calcium.
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ALKALINE PHOSPHATASE
 
Normally  alkaline  phosphatase  occurs  in  greatest  concentration  at  the 
intestinal  mucosa,  in  bone  and  in  the  kidney.    In  other  words,  it  functions 
principally  at  sites  at  absorption,  disposition  and  excretion  of  calcium  and 
phosphorus.  In bone, it is concentrated at the main points of ossification (i.e. 
the  epiphyseal  line  and  the  subperiosteal  area).    During  active  bone 
destruction,  a  compensatory  stimulation  of  osteoblasts  to  replace  bone  is 
reflected  in  an  increased  intracellular  content  of  alkaline  phosphatase  and 
increased  levels  in  the  bloodstream.    Because  it  is  present  in  large 
concentration  at  points  of  active  bone  formation,  the  Gomore  phosphatase 
stain may be used to identify areas of energetic new bone formation.
The  normal  range  of  blood  alkaline  phosphatase  relates  to  the  method 
used for assaying the enzyme.  The following are the normal ranges for the 
most commonly used procedures.
 -         1 - 4 units/dl  (Bodansky)
-         4 -13 units/dl (King Armstrong)
-         0.8 -2.5 units/dl (Bessey-Lowry)
-         30 -115 U/liter (SMAC)        www.indiandentalacademy.com
In children, the normal ranges are higher (e.g.: 5.0 to 14.8 Bodansky 
units/dl).
By  stains  that  are  specific  for  this  enzyme,  the  position  and 
concentration  of  alkaline  phosphatase  can  be  detected  in  the  tissues.   
Fibroblasts  in  the  outer  layers  of  periosteum  are  lacking  in  this  enzyme, 
whereas those in the cambium layer, where they are being differentiated into 
osteoblasts, contain large amount of this enzyme.  Stains identify the sites 
where  the  enzyme  is  located  as  being  intranuclear,  intracellular  or 
extracellular.
  Staining of the enzyme is useful for studying osteoblastic activity.  
For  example,  osteoblasts  and  their  precursors,  both  containing  alkaline 
phosphatase,  can  be  followed  about  a  bone  transplant  in  which  creeping 
substitution is taking place.  When new fibrocollagenous matrix is formed, 
osteoblasts  can  be  traced  to  their  ultimate  destiny,  which  are  not 
demonstrable by ordinary hematoxylin and eosin stain, because the nucleus 
losses  its  basophilic  staining  but  retains  its  affinity  for  the  alkaline 
phosphatase  stain.    As  the  osteoid  forms,  this  cell  disappears  and  alkaline 
phosphatase  is  no  longer  demonstrable.    It  appears  that  the  next  stage, 
namely mineralization, does not depend on alkaline phosphatase.
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ACID PHOSPHATASE
Acid  phosphatase  is  capable  of  hydrolyzing  hexose 
diphosphate  at  a  pH  of  5.    it  is  found  in  large  concentration  in  the 
prostate and in lesser amounts in the seminal vesicles, the testis, the 
epididymis and the spermatic duct.  The normal serum level of acid 
phosphatase  is  0.1  to  1.0  Bodansky  unit/dl.    It  appears  in  large 
amounts in the bloodstream in metastatic carcinoma of the prostate, 
even  before  bone  involvement  is  apparent  on  roentgenographic 
examination.  It is a counterpart of alkaline phosphatase and is present 
in cytoplasmic vesicles and vacuoles of osteoclast cell.
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BONE DEVELOPMENT
Although  histologically  one  bone  is  no  different  from  another  bone 
formation occurs by three mechanisms:
• Endochondral
• Intramembranous
• Sutural
 
Endochondral  bone 
formation  takes  place 
when  cartilage  is 
replaced  by  bone.   
Intramembranous                                  bone  formation  occurs  directly  within 
mesenchyme.  Sutural bone formation is a special case, the bone 
forming along sutural margins.www.indiandentalacademy.com
ENDOCHONDRAL BONE FORMATION
Endochondral  bone  formation  occurs  at  the  ends  of  all  long  bones, 
vertebrae,  ribs  and  at  the  head  of  the  mandible  and  base  of  the 
skull.  Early in embryonic development, there is a condensation of 
mesenchymal  cells.    Cartilage  cells  differentiate  from  these 
mesenchymal cells, chondroblast.
 
As  differentiation  of  cartilage  cells  proceeds  toward  the  metaphysis 
the cells organize themselves roughly into longitudinal columns.  
The  longitudinal  columns  of  cell  can  be  subdivided  into  three 
functionally different zones
• The zone of proliferation
• The zone of hypertrophy and maturation
• The zone of provisional mineralization                                        
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The  zone  of  hypertrophy  and 
maturation  is  the  broadest  zone.    The 
early  stages  of  hypertrophy  the 
chondroblasts  secrete  mainly  type  II 
collagen,  which  forms  the  primary 
structural  component  of  the 
longitudinal  matrix  septa.    The 
combination of increased cell size and 
increased  cell  secretion  leads  to  an 
increase in the size of the cartilaginous 
end of the bone.  As the chondroblast 
reaches maximum size, it secretes type 
X  collagen,  chondrocalcin,  and  bone 
sialoprotein,  which  create  a  matrix 
environment  with  the  potential  to 
mineralize  matrix.  Mineralization 
begins in the zone of mineralization.
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Within  the  perichondrium  in  the  diaphysis,  there  is  increased 
vascularization, perichondrium coverts to a periosteum and intramembranous 
bone  begins  to  form.    The  middle  of  the  cartilage  occurs,  cells  called 
chondroclasts resorb most of the mineralized cartilage matrix, making room 
for further vascular in growth.
Mesenchymal  (perivascular)  cells  accompany  the  invading  blood 
vessels,  proliferating  and  migrating  onto  the  remains  of  the  mineralized 
cartilage matrix.  The mesenchymal cells differentiate into obsteoblasts and 
begin  to  deposit  osteoid  on  the  mineralized  cartilage  columns  and  then  to 
mineralize it.  as the bone matrix is produced, the mineralized cartilage matrix 
becomes  an  irregularly  shaped  central  zone  core  for  a  circular  rim  of  new 
bone  matrix.    Some  of  the  osteoblasts  are  surrounded  by  bone  matrix  and 
become osteocytes.  Collectively termed the primary spongiosa.  As the bone 
grow  longer,  the  marrow  continues  to  expand.    Osteoclasts  progressively 
remove both the core of mineralized cartilage and the surrounding bone.  This 
process  occurs  at  approximately  the  same  rate  as  cartilage  formation,  so 
volume of the primary spongiosa remains relatively constant. 
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Oseoclasts  also expand 
the marrow cavity along 
the  entire  endosteal 
surface.    A  plate  of 
growing  cartilage 
remaining  between  the 
diaphysis  and  the  end 
(epiphysis) of the bone.  
This plate is termed the 
epiphyseal growth plate. 
 Longitudinal bone            growth  ceases  when  the  cartilage  cells  stop 
proliferating and the growth plate disappears as longitudinal bone 
growth slows and ceases the expansion of the marrow cavity stops.
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INTRAMEMBRANOUS BONE FORMATION
In  intramembranous  bone  formation,  bone  develops  directly  within  the 
soft connective tissue rather than on the cartilaginous model.  The mesenchymal 
cells  proliferate  and  condense.    As  vascularity  increases  at  these  sites  of 
condensed  mesenchyme,  osteoblasts  differentiate  and  begin  to  produce  bone 
matrix.  This occurs at multiple sites within each bone of the cranial vault, maxilla 
body of the mandible and midshaft of long bones
Once begun intramembranous bone formation proceeds at an extremely 
rapid rate.  This first embryonic bone is termed coarse fibered woven bone.  At 
first the woven bone takes the form of radiating spicules, but progressively the 
spicules fuse into thin bony plates.  In the cranium, more than one of these plates 
may fuse to form a single bone.  The establishment and expansion of the marrow 
cavity  turns  the  endosteum  into  primarily  a  resorbing  surface,  whereas  the 
periosteum  initiates  the  formation  of  most  of  the  new  bone.Segments  of  the 
periosteal  surface  of  an  individual  bone  may  contain  focal  sites  of  bone 
resorption.  For instance, growth of the brain nasal cavity and the lengthening of 
the body of the mandible all require focal resorption along the periosteal surface.  
Conversely,  segments  of  the  endosteum  of  the  same  bone  may  simultaneously 
become a forming surface, resulting in bone drift.www.indiandentalacademy.com
    connective tissue surrounded by trabecular of 
surface vessels. The primary osteon tends to be relatively small, the collagen 
fibers are slightly better organized, soft tissue derived fibrils are absent, and 
the  degree  of  mineralization  is  greater.As  more  osteons  are  formed  at  the 
periosteal surface, they become more tightly packed.
From  early  fetal  development 
to full expression of the adult 
skeleton,  there  is  a  continual 
slow  transition  from  woven 
bone  to  lamellar  bone.    Bone 
formed during the transition is 
called immature bone 
This  transition 
involves  the  formation  of 
primary  osteons  deposited 
around a blood vessel in the
www.indiandentalacademy.com
REFERENCES
1. Text book of Medical Physiology – Guyton and Hall – 9th
Edition
2. Principles of Anatomy and Physiology – Gerard J. Tortora – 6th
& 8th
Editions
3. Gray’s Anatomy – Peter L. Williams – 38th
Edition
4. Oral Histology – Richard Tencate – 5th
Edition
5. Orban’s Oral Histology and Embryology – S.N. Bhaskar – 10th
Edition
6. Harper’s Biochemistry – Robert K. Murray – 23rd
Edition
7. Fundamentals of Biochemistry – A.C Deb – 6th
Edition
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Dental tissues and their replacements/ oral surgery courses  
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Bone or osseous tissue/ oral surgery courses

  • 1. CONTENTS • Introduction • Functions of bone • Division of skeletal system • Classification of bone • Structural anatomy of long bones • Composition of bone • Bone development INDIAN DENTAL ACADEMY Leader in continuing Dental Education www.indiandentalacademy.com
  • 2. INTRODUCTION Bone or osseous tissue represents the highest differentiation among supporting tissues. It is rigid tissue that constitutes most of the skeleton of higher vertebrates. Skeleton : Bony and cartilaginous framework of the body constitutes the skeleton. Endoskeleton : Where the skeleton is located internally on the body. In human anatomy, the term skeleton usually means endoskeleton. Exoskeleton : In some vertebrates, the skeletal framework is found both externally (exoskeleton) and internally (endoskeleton). In human beings the exoskeleton is very rudimentary, being represented by nails and enamel of teeth only. www.indiandentalacademy.com
  • 3. Bone, in common with other connective tissues, consists of cells, fibres and ground substance, but unlike the others, its extra cellular components are calcified, making it a hard, unyielding substance ideally suited for its supportive and protective function in the skeleton. The alveolar process is the bone that forms and supports the tooth sockets (alveoli). It forms when the tooth erupts in order to provide the osseous attachments to the forming periodontal ligament, it disappears gradually when the tooth is lost. www.indiandentalacademy.com
  • 4. 1. Support : The skeleton provides a framework for the body, and as such, it supports soft tissues and provides a point of attachment for many muscles. 2. Protection : Many internal organs are protected from injury by the skeleton. For example, the brain is protected by the cranial bones, the spinal cord by the vertebrae, the heart and lungs by the rib cage, and internal reproductive organs by the pelvic bones. 3. Movement facilitation : Bones serve as levers to which muscles are attached. When the muscles contract, bones acting as levers and movable joints acting as fulcrums produce movement. 4. Mineral Storage : Bones store several minerals that can be distributed to other parts of the body upon demand. The principal stored minerals are calcium and phosphorus.www.indiandentalacademy.com
  • 5. 5. Storage of blood cell-producing cells: Red marrow in certain bones is capable of producing blood cells, a process called hematopoiesis (hem-a-to-poy-E-sis) or hemopoiesis. Red marrow consists of blood cells in immature stages, fat cells, and macrophages. Red marrow produces red blood cells, some white blood cells, and platelets. 6. Storage of energy : Lipids stored in cells of yellow marrow are an important source of chemical energy. www.indiandentalacademy.com
  • 6. DIVISIONS OF THE SKELETAL SYSTEM REGIONS OF THE SKELETON NUMBER OF BONES AXIAL SKELETON Skull Cranium 8 Face 14 Hyoid 1 Auditery ossicles (3 in each ear) 6 Vertebral column 26 Thorax Sternum 1 Ribs 24 80 www.indiandentalacademy.com
  • 7. APPENDICULAR SKELETON Pectoral (shoulder) girdles Clavicle 2 Scapula 2 Upper extremities Humerus 2 Ulna 2 Radius 2 Carpals 16 Metacarpals 10 Phalanges 28 Pelvic (hip) girdle Coxal, Pelvic or hip bone 2 Lower extremities Femur 2 Fibula 2 Tibia 2 Patella 2 Tarsals 14 Metatarsals 10 Phalanges 28 126 Total = 206www.indiandentalacademy.com
  • 8. CRANIAL BONES a. Frontal Bone 1 b. Parietal Bone 2 c. Temporal Bone 2 d. Occipital Bone 1 e. Sphenoid Bone 1 f. Ethmoid Bone 1 ab c d e f www.indiandentalacademy.com
  • 9. FACIAL BONES Nasal Bone 2 Maxillae 2 Zygomatic Bones 2 Mandible 1 Lacrimal Bones 2 Palatine Bones 2 Inferior Nasal Conchae 2 Vomer 1 www.indiandentalacademy.com
  • 10. CLASSIFICATION OF BONES A. According to Position 1. Axial : Bones forming the axis of the body, e.g., skull, ribs, sternum and vertebrae. 2. Appendicular : Bones forming the skeleton of limbs (appendages of the body). www.indiandentalacademy.com
  • 11. B. According to Size and Shape 1. Long Bones : present in upper and lower limbs. Possess three parts : (i) upper end (ii) shaft (iii) lower end. The two ends are usually expanded for forming articulations and giving attachments to muscles and ligaments. The shaft is tubular with a central medullary cavity. Examples : Humerus, radius, ulna, femur, tibia and fibula. Long bones act as levers for movements and locomotion. 2. Short long bones : Same as above but are miniature in size. The length of bone exceeds other measurements. Examples : Metacarpals, metatarsals and phalanges. 3. Short Bones : Small, polyhedral and generally cuboidal in shape. Examples : Carpal and tarsal bones. Short bones provide strength and compactness but range of movement is limited. 4. Flat Bones : Expanded and plate like. They protect vital structure and provide extensive areas for muscular attachment. Examples : Scapula, sternum, ribs, parietal and frontal bones. www.indiandentalacademy.com
  • 12. 5. Irregular bones : Irregular in general outline and do not fit in any of the above categories. Examples : Vertebrae, some skull bones. 6. Pneumatic bones : Flat or irregular bones possessing a hollow space within their body which contains air. Presence of air filled spaces provide economical methods of expansion of bones in size and make them lighter. Examples : Ethmoid, maxilla, mastoid part of temporal bone. 7. Sesamoid bones : Sesamoid means “seed like”. They are nodules of bone which develop in certain tendons and do not possess periosteum and Haversian systems. They ossify after birth. They diminish friction, modify and may also change the direction of the pull of muscle. Examples : Pisiform, patella (which is the largest sesamoid bone and develops in quadriceps femoris tendon). www.indiandentalacademy.com
  • 13. C. According to Gross Structure 1. Compact (Lamellar) Bone : the outer cortical part of long bones, which is hard and has a homogeneous appearance. 2.Spongy (cancellous) Bone : The inner part of bone which is less hard and presents a spongy appearance. Examples :Flat, Short and Irregular Bones and ends of long bones. 3.Diploic Bone : Consists of inner and outer tables of compact bone with an intervening porous layer which is occupied by a spongy substance consisting of bone marrow and diploic veins e.g., most of cranial bones. D. According to Development Embroyonic mesenchymatous tissue is the precursor of a bone, further development occurs by two methods. 1. Membranous (Ectochondral) bones : Which develop in membrane. 2. Cartilaginous (Endochondral) bones : Which develop in cartilage. www.indiandentalacademy.com
  • 14. Structural Anatomy of Long Bone 1. Diaphysis ( dia = through; physis = growth). The shaft or long, main portion of the bone. 2. Epiphyses (epi=above: physis = growth). The extremities or ends of the bone (singular is epiphysis). 3. Metaphysis (me-TAF-I-sis). The region in a mature bone where the diaphysis joins the epiphysis. In a growing bone, it is the region including the epiphyseal plate where cartilage is reinforced and then replaced by bone. 4. Articular cartilage : A thin layer of hyaline cartilage covering the epiphysis where the bone forms a joint with another bone. The cartilage reduces friction and absorbs shock at freely movable joints. www.indiandentalacademy.com
  • 15. 5. Periosteum : (peri= around;osteo= bone) A dense, white, fibrous covering around the surface of the bone not covered by articular cartilage. The periosteum consists of two layers. The outer fibrous layer is composed of connective tissue containing blood vessels, lymphatic vessels, and nerves that pass into the bone. The inner osteogenic layer contains elastic fibers, blood vessels, osteoprogenitor cells, osteoclasts, and osteoblasts. The periosteum is essential for bone growth, repair, and nutrition. It also serves as a point of attachment for ligaments and tendons. 6. Medullary or marrow cavity. The space within the diaphysis that contains the fatty yellow marrow in adults. Yellow marrow consists primarily of fat cells and a few scattered blood cells. Thus, yellow marrow functions in fat storage. 7. Endosteum. A layer of osteoprogenitor cells and osteoblasts that lines and medullary cavity and also contains scattered osteoclasts (cells that assume a role in the removal of bone). www.indiandentalacademy.com
  • 17. Bone is not completely solid. In fact, all bone has some spaces between its hard components. The spaces provide channels for blood vessels that supply bone cells with nutrients. The spaces also make bones lighter. Depending on the size and distribution of the spaces, the regions of a bone may be categorized as compact or spongy. www.indiandentalacademy.com
  • 18. The layer of compact bone is thicker in the diaphysis than the epiphyses. Compact bone tissue provides protection and support and helps the long bones resist the stress of weight placed on them. One main difference is that adult compact bone has a concentric ring structure, whereas spongy bone does not. Blood vessels and nerves from the periosteum penetrate the compact bone through perforating (volkmann’s) canals. The blood vessels of these canals connect with blood vessels and nerves of the medullary cavity and those of the central (Haversian) canals. The central canals run longitudinally through the bone. Around the canals are concentric lamellae rings of hard, calcified, intercellular substance. Between the lamellae are small spaces called lacunae. Which contain osteocytes, Osteocytes, as noted earlier, are mature osteoblasts that no longer produce new bone tissue and function to support daily cellular activities of bone tissue. COMPACT BONE www.indiandentalacademy.com
  • 19. Radiating in all directions from the lacunae are minute canals called canaliculi. The canaliculi connect with those of other lacunae and, eventually, with the central canals. An intricate network is formed throughout the bone. Provides numerous routes so that nutrients can reach the osteocytes and wastes can be removed. Each central canal, with its surrounding lamellae, lacunae, osteocytes and canaliculi, is called an osteon (Haversian system). The areas between osteons contain interstitial lamellae. www.indiandentalacademy.com
  • 20. SPONGY BONE Spongy bone does not contain true osteons. It consists of an irregular latticework of thin plates of bone called Trabeculae. The spaces between the trabeculae of some bones are filled with red marrow. The cells of red marrow are responsible for producing blood cells. Within the trabeculae lie lacunae, which contain osteocytes. www.indiandentalacademy.com
  • 21. COMPOSITION OF BONE Cells of Bone - Osteoprogenitor cells - Osteoblast cells. - Osteocytes - Osteoclast cells. Organic part – 33% - 35% Collagen – 88% - 90% (Type – I) Non collagen – 10% - 11%. Glycoproteins – 6% - 9% (Mono, di, poly and oligosaccharides). Proteoglycanes – 0.8% (sulfated and Non sulfated) Sialoproteins – 0.35% Lipids – 0.4% Inorganic Part – 65% - 67% - Calcium & Phosphates – 95% (Hydroxyapatite Crystals – Ca10 (Po4 )6 (OH)2 ) - Magnesium - Trace elements – Nickel, Iron, Fluoride, Cadmium, Magnesium, Zinc and Molybdenum. www.indiandentalacademy.com
  • 23. Osteoblasts Osteoblasts are uninucleated cells that synthesized both collagenous and noncollagenous bone protein. They are responsible for mineralization and are derived from a multipotent mesenchymal cell. Osteoblasts have all the characteristics of hard tissue forming cells. They constitute a cellular layer over the forming bone surface. When bone is no longer forming, the surface osteoblasts become inactive and are termed lining cells(bone maintenance) Osteoblasts exhibit high levels of alkaline phosphate on the outer surface of their plasma membranes,this distinguishes the ostioblast from the fibroblast www.indiandentalacademy.com
  • 24. Other enzymes that participate in there activity are ATPase and pyrophosphates. Osteoblasts secrete, in addition to type I and type V collagen and small amounts of several noncollagenous proteins, a variety of cytokines. Osteoblasts under the stimulation of interleukin 6 also produce their own hydrolytic enzymes that aid in destroying or modifying the unmineralized matrix. Thus freeing the osteoblast from its own secreted matrix. The hormones most important in bone metabolism are parathyroid hormone. 1,25 dihydroxyvitamin D, calcitonin, estrogen, and the glucocorticoids,which have a influence on osteoblasts. www.indiandentalacademy.com
  • 25. As osteoblasts secrete bone matrix, some of them become entrapped in lacunae and are then called osteocytes. The number of osteoblasts that become osteocytes varies depending on the rapidity of bone formation. The more rapid the formation, a more osteocytes are present per unit volume. As a general rule, embryonic bone and repair bone have more osteocytes than does lamellar bone. Osteocyte Osteocytes gradually lose most of their matrix synthesizing machinery and become reduced in size. The space in the matrix occupied by an osteocyte is called the osteocytic lacuna. Narrow extensions of these or canaliculi, that form radiating osteocytic processes maintain contact with adjacent osteocytes and osteoblasts the endosteum, periosteum, and Haversian canals. Failure of any part of this inter connecting system result in hyper mineralization (sclerosis) and death of the bone.www.indiandentalacademy.com
  • 26. Osteoclast Compared to all other bone cells and their precursors, the multinucleated osteoclast is a much larger cell. Because of their size, be identified under the light microscopy, generally seen in a cluster rather than singly. The osteoclast is characterized by acid phosphatase within its cytoplasmic vesicles and vacuoles, which distinguishes it from other giant cells and macrophages. Typically osteoclasts are found against the bone surface occupying shallow, hollowed out depressions, called Howship’s lacunae. www.indiandentalacademy.com
  • 27. Adjacent to the tissue surface, their cell membrane is thrown into a myriad of deep folds that form a brush border. This clear or “sealing” zone attached the cells to the mineralized surface. Isolates a micro environment between them and the bone surface. The cell organelles consist of many nuclei, each surrounded by multiple Golgi complexes, an array of mitochondria and free polysomes, a rough endoplasmic reticulum, many coated transport vesicles, and numerous vacuolar structures. Osteoblast are also rich in lysosomal enzymes. www.indiandentalacademy.com
  • 28. Thus the sequence of resorptive events is considered to be 1. Attachment of osteoclasts to the mineralized surface of bone. 2. Creation of a sealed acidic environment through action of the proton pump, which demineralizes bone and exposes the organic matrix. 3. Degradation of this exposed organic matrix to its constituent amino acids by the action of released enzymes. 4. Uptake of mineral ions and amino acids by the cell. www.indiandentalacademy.com
  • 29. Organic part – 33% - 35% Collagen – 88% - 90% (Type – I) Non collagen – 10% - 11%. Glycoproteins – 6% - 9% (Mono, di, poly and oligosaccharides). Proteoglycanes – 0.8% (sulfated and Non sulfated) Sialoproteins – 0.35% Lipids – 0.4% www.indiandentalacademy.com
  • 30. Collagen forms a highly ordered system of collagen fibers with the typical axial periodicity of 640 A° to 700 A° and a unique protein composition of about one third glycine residues, one fifth amino acid residues, a large number of alanine residues and very few aromatic amino acids, Cysteine in completely lacking. A single collagen fibril is a three standard coil composed of three adjacent left handed helixes (designated collagen polymers al, al, a2) bound together by intromolecular cross linkage and twisted about a common axis. COLLAGEN www.indiandentalacademy.com
  • 31. When newly synthesized (Young ) collagen is denatured, it separates into two al chains and one a2 chain, each with a molecular weight of about 100,000. Other collagen gives rise to two double and one triple chain (B11, B12, and Y112) whose molecular weights are 200,000 and 300,000 respectively. Although the composition of bone collagen is similar to other types of collagen, it is insoluble in solvents used to extract collagens from other tissues (neutral salt solutions and weak organic acids). This characteristic is thought to be due to the presence of strong intermolecular bonds between and along the length of adjacent macromolecules. www.indiandentalacademy.com
  • 32. PROTEINPOLYSACCHARIDES Proteinpolysaccharides (PPS) comprise 4% to 5% of the organic constituents of bone. They are compounds consisting of a polypeptide chain to which side chains of highly sulfated polysaccharides are covalently bound. The principal polysaccharides of bone of chondroitin-4 sulfate (Chondroitin sulfate A). Its role is not clear, but it appears to inhibit mineralization of bone by strongly completing with Ca2+ ions. In certain diseases (eg.: the mucopolysaccharidoses) increased urinary excretion of polysaccharides takes place. The loss of polysaccharides form bone and cartilage results in specific skeletal deformities. Noncollagenous protein amounts to about 0.5% of the organic constituents, but most of this fraction represents the protein core of PPS. LIPIDS Less than 0.4% of the organic constituents of bone is composed of lipids, consisting of triglycerides, free fatty acids, phospholipids and cholesterol. www.indiandentalacademy.com
  • 33. INORGANIC CONSTITUTENTS The dry weight of bone is composed of 65% to 67% inorganic mineral, 95% of which is a calcium and phosphate solid. An “amorphous” Ca-P solid is present in greater amounts in young newly formed tissue (40% to 50%) than in older, more mature bone (25% to 30%). Only about 0.65% of human bone calcium is part of a readily exchangeable pool. The sites where rapid exchange takes place can be identified by radionuclides and appear to be the lining of the haversian canals and resorption cavities. www.indiandentalacademy.com
  • 34. CALCIUM Calcium salts are relatively insoluble, especially as phosphates and carbonates. The secondary form of calcium phosphate, CaHPO4 has solubility of greater than 10-3 M and the ions of this form circulate in the ECF at approximately half this concentration. Calcium is complexed by many organic compounds, particularly proteins. This characteristics is essential to strengthening and regulating the permeability of the cell membrane. For the normal functioning of cells, intra cellular Ca2+ ion concentration must be maintained in the range of 10 –7 M. A normal PH must be maintained and concentrations of Ca2+ and HPO4 ions must not exceed the range of 10 –3 M to avoid calcium phosphate precipitation within the cell. The calcium ion, when absorbed by the intestinal mucosa, or during renal tubular resorption after glomerular filtration, must be transported though the cell itself and pumped out of the cell with sufficient rapidity to avoid disturbing the cellular processes. Calcium concentration in plasma is approximately 10 mg / dl. www.indiandentalacademy.com
  • 35. The dominant role in the maintenance of calcium homestasis is played by the constant resorption and deposition of bone minerals throughout life. To a lesser degree, other internal factors such as hormonal Parathyroid hormone (PTH), calcitonin (renal tubular resorption) and vitamin D metabolites exert roles that help to maintain constant plasma calcium concentrations. The surface of active bone tissue are covered by a layer of cells that form a dynamic interface between the fluid in contact with the inter cellular components of bone and the ECF.Calcium ions in bone, intestine and kidney are transported though the cell toward the ECF. The source of ions in the gut is the dietary intake; ions transported through the renal tubule are derived from the glomerular filtrate. www.indiandentalacademy.com
  • 36. Intestinal absorption depends on dietary sources plus factors that influences this absorption (eg. Vitamin D metabolites), bile salts to emulsify the fats (to facilitate fat-soluble vitamin D absorption), PTH and calcitonin. In the absence of adequate oral intake, the renal tubular absorption approaches 100%, whereas the bone surface returns more than 100%. VITAMIN D (CHOLECALCIFEROL) Angus and coworkers isolated vitamin D in 1931 and named it as calciferol. The production of vitamin D in the skin is directly proportional to the exposure to sunlight and inversely proportional to the pigmentation of skin. Melanin is a natural sunscreen. The cholecalciferol is first transported to liver, where hydroxylation occurs, to form 25 hydroxy cholecalciferol and is the major transport form. In the kidney, it is further hydroxylated at the 1st position forming 1,25-dihydroxy cholecalciferol, also called Calcitriol, the active form of the vitamin. www.indiandentalacademy.com
  • 37. Effects: a) Intestinal villi cells b) Bone osteoblasts c) Distal tubular cells of Kidney www.indiandentalacademy.com
  • 38. Vitamin D and Intestinal Absorption of Calcium: Calcitriol promotes the absorption of calcium and phosphorus from the intestine. In the brush-border surface, calcium is absorbed passively. From the intestinal cell to blood, absorption of calcium needs energy. It is either by the sodium-calcium exchange mechanism or calcium-calbindin complex. Calcitriol acts like a steroid hormone. It enters the target cell and binds to a cytoplasmic receptor, Calbindin. Due to the increased availability of calcium binding protein, the absorption of calcium is increased. Effect of Vitamin D in Bone: Mineralisation of the bone is increased by increasing the activity of osteoblasts. It produces the differentiation of osteoclast precursors from multinucleated cells of osteoblast lineage. Calcitriol stimulates osteoblasts which secrete alkaline phosphatase. Due to this enzyme, the local concentration of phosphate is increased. The ionic product of calcium and phosphorus increases, leading to mineralisation. Effect of Vitamin D in Renal Tubules: Calcitriol increases the reabsorption of calcium and phosphorus by renal tubules, therefore both minerals are conserved. www.indiandentalacademy.com
  • 39. PARATHYROID HORMONE (PTH): Ivar Sandstrom discovered the parathyroid glands in 1880. In 1926, Collip isolated the PTH. This hormone is secreted by the four parathyroid glands embedded in the thyroid tissue. The chief cells of the gland secrete the PTH. Storage of PTH is only for about one hour. Control of release of the hormone is by negative feedback by the ionized calcium in serum. Normal PTH level in serum is 10-60 ng/L. The PTH has three major independent sites of action; bone, kidney and intestines. All the three actions of PTH increase serum calcium level. www.indiandentalacademy.com
  • 40. In the bone PTH causes demineralization or decalcification. It induces pyrophosphatase in the osteoclasts. The numbers of osteoclasts are also increased (release lactate). PTH also causes secretion of collagenase from osteoclasts. This causes loss of matrix and bone resorption. In Kidney PTH causes decreased renal excretion of calcium and increased excretion of phosphates. The action is mainly through increase in reabsorption of calcium from kidney tubules. PTH stimulates 1- hydroxylation of 25 hydroxycalciferol in kidney to produce calcitriol. This from intestine. indirectly increases calcium absorptionwww.indiandentalacademy.com
  • 41. Calcitonin: Hirsch isolated it in 1962. It is secreted by the thyroid parafollicular or clear cells. Calcitonin secretion is stimulated by serum calcium. Calcitonin decreases serum calcium level. It inhibits resorption of bone. It decreases the activity of osteoclasts and increases that of osteoblasts. Calcitonin together promote the bone growth and remodeling. In kidney, calcitonin increases phosphorus excretion through urine; this action is similar to PTH. www.indiandentalacademy.com
  • 42. Vitamin D PTH Calcitonin Blood calcium Increased Drastically increased Decreased Main action Absorption from gut Demineralisation Opposes demineralization Calcium absorption from gut Increased Increased (Indirect) Bone resorption Decreased Increased Decreased Deficiency manifestation Rickets Tetany Use in rickets Drug of choice Contra indicated Theoretically beneficial Effect of excess Hypercalcemia+ Hypercalcemia+ + Hypocalcemia Comparison of action of three major factors affecting serum calcium www.indiandentalacademy.com
  • 43. PHOSPHORUS Phosphorus exists as a completely ionized inorganic phosphate in the bloodstream. Eighty percent of the mineral in the body resides in the skeleton, where it is combined with calcium as a complete hydroxyapatite, the formula for which is approximately Ca10 (PO4 )6 (OH)2 . Phosphate in bone consists of a labile fraction, which is in equilibrium with the phosphate ions in the blood stream and stable fraction, which is fixed in the skeleton. The minimum daily requirements in the normal adult is 0.88 g and is slightly more for growing children and pregnant women. The main food source of phosphorus is milk, with smaller amounts obtained form meat, cheese, eggs, nuts and whole cereal. While flour and rice have a small content. Phosphorus exists in food in both organic and inorganic forms. Absorption takes place from the small intestine in the form of soluble inorganic phosphate. An excess of ingested calcium encourages the precipitation of insoluble phosphates within the intestinal lumen, thereby lessening the absorption of phosphate. As an result the serum phosphate level is lowered, leading to hypophosphatemic rickets or osteomalacia. www.indiandentalacademy.com
  • 44. When ingested calcium is inadequate, a relative excess of serum phosphates exists. Serum calcium levels must be stored chiefly by compensatory hyperparathyroidism, which causes bone resorption, increases phosphate urinary excretion and decreases its tubular resorption. The normal level of serum phosphate as ionized inorganic phosphate is 3mmg to 4mg/dl in the adult and 5mg to 6 mg/dl in the infant. Excretion takes place principally in the urine as monosodium (acid) or disodium (alkaline) phosphates and in lesser amounts as a salt of potassium, ammonium, calcium and magnesium. Ninety percent of excreted phosphate is in the inorganic form. www.indiandentalacademy.com
  • 45. The urinary excretion of phosphate mainly depends on dietary intake, which must be carefully controlled for several days before determinations can be made of intake output, serum levels and renal tubular resoption rates. The normal range of urinary excretion for adults is 340mg to 840mg /day, whereas that for children is 530mg to 840 mg/day. Values above or below these levels are considered abnormal. Calcium inhibits bone resorption, thereby lowering the serum phosphate level, which in turn reduces the amount of phosphate excreted by the kidneys. Calcitonin also directly inhibits tubular resorption of calcium. www.indiandentalacademy.com
  • 46. ALKALINE PHOSPHATASE   Normally  alkaline  phosphatase  occurs  in  greatest  concentration  at  the  intestinal  mucosa,  in  bone  and  in  the  kidney.    In  other  words,  it  functions  principally  at  sites  at  absorption,  disposition  and  excretion  of  calcium  and  phosphorus.  In bone, it is concentrated at the main points of ossification (i.e.  the  epiphyseal  line  and  the  subperiosteal  area).    During  active  bone  destruction,  a  compensatory  stimulation  of  osteoblasts  to  replace  bone  is  reflected  in  an  increased  intracellular  content  of  alkaline  phosphatase  and  increased  levels  in  the  bloodstream.    Because  it  is  present  in  large  concentration  at  points  of  active  bone  formation,  the  Gomore  phosphatase  stain may be used to identify areas of energetic new bone formation. The  normal  range  of  blood  alkaline  phosphatase  relates  to  the  method  used for assaying the enzyme.  The following are the normal ranges for the  most commonly used procedures.  -         1 - 4 units/dl  (Bodansky) -         4 -13 units/dl (King Armstrong) -         0.8 -2.5 units/dl (Bessey-Lowry) -         30 -115 U/liter (SMAC)        www.indiandentalacademy.com
  • 47. In children, the normal ranges are higher (e.g.: 5.0 to 14.8 Bodansky  units/dl). By  stains  that  are  specific  for  this  enzyme,  the  position  and  concentration  of  alkaline  phosphatase  can  be  detected  in  the  tissues.    Fibroblasts  in  the  outer  layers  of  periosteum  are  lacking  in  this  enzyme,  whereas those in the cambium layer, where they are being differentiated into  osteoblasts, contain large amount of this enzyme.  Stains identify the sites  where  the  enzyme  is  located  as  being  intranuclear,  intracellular  or  extracellular.   Staining of the enzyme is useful for studying osteoblastic activity.   For  example,  osteoblasts  and  their  precursors,  both  containing  alkaline  phosphatase,  can  be  followed  about  a  bone  transplant  in  which  creeping  substitution is taking place.  When new fibrocollagenous matrix is formed,  osteoblasts  can  be  traced  to  their  ultimate  destiny,  which  are  not  demonstrable by ordinary hematoxylin and eosin stain, because the nucleus  losses  its  basophilic  staining  but  retains  its  affinity  for  the  alkaline  phosphatase  stain.    As  the  osteoid  forms,  this  cell  disappears  and  alkaline  phosphatase  is  no  longer  demonstrable.    It  appears  that  the  next  stage,  namely mineralization, does not depend on alkaline phosphatase. www.indiandentalacademy.com
  • 49. ACID PHOSPHATASE Acid  phosphatase  is  capable  of  hydrolyzing  hexose  diphosphate  at  a  pH  of  5.    it  is  found  in  large  concentration  in  the  prostate and in lesser amounts in the seminal vesicles, the testis, the  epididymis and the spermatic duct.  The normal serum level of acid  phosphatase  is  0.1  to  1.0  Bodansky  unit/dl.    It  appears  in  large  amounts in the bloodstream in metastatic carcinoma of the prostate,  even  before  bone  involvement  is  apparent  on  roentgenographic  examination.  It is a counterpart of alkaline phosphatase and is present  in cytoplasmic vesicles and vacuoles of osteoclast cell. www.indiandentalacademy.com
  • 50. BONE DEVELOPMENT Although  histologically  one  bone  is  no  different  from  another  bone  formation occurs by three mechanisms: • Endochondral • Intramembranous • Sutural   Endochondral  bone  formation  takes  place  when  cartilage  is  replaced  by  bone.    Intramembranous                                  bone  formation  occurs  directly  within  mesenchyme.  Sutural bone formation is a special case, the bone  forming along sutural margins.www.indiandentalacademy.com
  • 51. ENDOCHONDRAL BONE FORMATION Endochondral  bone  formation  occurs  at  the  ends  of  all  long  bones,  vertebrae,  ribs  and  at  the  head  of  the  mandible  and  base  of  the  skull.  Early in embryonic development, there is a condensation of  mesenchymal  cells.    Cartilage  cells  differentiate  from  these  mesenchymal cells, chondroblast.   As  differentiation  of  cartilage  cells  proceeds  toward  the  metaphysis  the cells organize themselves roughly into longitudinal columns.   The  longitudinal  columns  of  cell  can  be  subdivided  into  three  functionally different zones • The zone of proliferation • The zone of hypertrophy and maturation • The zone of provisional mineralization                                         www.indiandentalacademy.com
  • 53. The  zone  of  hypertrophy  and  maturation  is  the  broadest  zone.    The  early  stages  of  hypertrophy  the  chondroblasts  secrete  mainly  type  II  collagen,  which  forms  the  primary  structural  component  of  the  longitudinal  matrix  septa.    The  combination of increased cell size and  increased  cell  secretion  leads  to  an  increase in the size of the cartilaginous  end of the bone.  As the chondroblast  reaches maximum size, it secretes type  X  collagen,  chondrocalcin,  and  bone  sialoprotein,  which  create  a  matrix  environment  with  the  potential  to  mineralize  matrix.  Mineralization  begins in the zone of mineralization. www.indiandentalacademy.com
  • 54. Within  the  perichondrium  in  the  diaphysis,  there  is  increased  vascularization, perichondrium coverts to a periosteum and intramembranous  bone  begins  to  form.    The  middle  of  the  cartilage  occurs,  cells  called  chondroclasts resorb most of the mineralized cartilage matrix, making room  for further vascular in growth. Mesenchymal  (perivascular)  cells  accompany  the  invading  blood  vessels,  proliferating  and  migrating  onto  the  remains  of  the  mineralized  cartilage matrix.  The mesenchymal cells differentiate into obsteoblasts and  begin  to  deposit  osteoid  on  the  mineralized  cartilage  columns  and  then  to  mineralize it.  as the bone matrix is produced, the mineralized cartilage matrix  becomes  an  irregularly  shaped  central  zone  core  for  a  circular  rim  of  new  bone  matrix.    Some  of  the  osteoblasts  are  surrounded  by  bone  matrix  and  become osteocytes.  Collectively termed the primary spongiosa.  As the bone  grow  longer,  the  marrow  continues  to  expand.    Osteoclasts  progressively  remove both the core of mineralized cartilage and the surrounding bone.  This  process  occurs  at  approximately  the  same  rate  as  cartilage  formation,  so  volume of the primary spongiosa remains relatively constant.  www.indiandentalacademy.com
  • 55. Oseoclasts  also expand  the marrow cavity along  the  entire  endosteal  surface.    A  plate  of  growing  cartilage  remaining  between  the  diaphysis  and  the  end  (epiphysis) of the bone.   This plate is termed the  epiphyseal growth plate.   Longitudinal bone            growth  ceases  when  the  cartilage  cells  stop  proliferating and the growth plate disappears as longitudinal bone  growth slows and ceases the expansion of the marrow cavity stops. www.indiandentalacademy.com
  • 56. INTRAMEMBRANOUS BONE FORMATION In  intramembranous  bone  formation,  bone  develops  directly  within  the  soft connective tissue rather than on the cartilaginous model.  The mesenchymal  cells  proliferate  and  condense.    As  vascularity  increases  at  these  sites  of  condensed  mesenchyme,  osteoblasts  differentiate  and  begin  to  produce  bone  matrix.  This occurs at multiple sites within each bone of the cranial vault, maxilla  body of the mandible and midshaft of long bones Once begun intramembranous bone formation proceeds at an extremely  rapid rate.  This first embryonic bone is termed coarse fibered woven bone.  At  first the woven bone takes the form of radiating spicules, but progressively the  spicules fuse into thin bony plates.  In the cranium, more than one of these plates  may fuse to form a single bone.  The establishment and expansion of the marrow  cavity  turns  the  endosteum  into  primarily  a  resorbing  surface,  whereas  the  periosteum  initiates  the  formation  of  most  of  the  new  bone.Segments  of  the  periosteal  surface  of  an  individual  bone  may  contain  focal  sites  of  bone  resorption.  For instance, growth of the brain nasal cavity and the lengthening of  the body of the mandible all require focal resorption along the periosteal surface.   Conversely,  segments  of  the  endosteum  of  the  same  bone  may  simultaneously  become a forming surface, resulting in bone drift.www.indiandentalacademy.com
  • 57.     connective tissue surrounded by trabecular of  surface vessels. The primary osteon tends to be relatively small, the collagen  fibers are slightly better organized, soft tissue derived fibrils are absent, and  the  degree  of  mineralization  is  greater.As  more  osteons  are  formed  at  the  periosteal surface, they become more tightly packed. From  early  fetal  development  to full expression of the adult  skeleton,  there  is  a  continual  slow  transition  from  woven  bone  to  lamellar  bone.    Bone  formed during the transition is  called immature bone  This  transition  involves  the  formation  of  primary  osteons  deposited  around a blood vessel in the www.indiandentalacademy.com
  • 58. REFERENCES 1. Text book of Medical Physiology – Guyton and Hall – 9th Edition 2. Principles of Anatomy and Physiology – Gerard J. Tortora – 6th & 8th Editions 3. Gray’s Anatomy – Peter L. Williams – 38th Edition 4. Oral Histology – Richard Tencate – 5th Edition 5. Orban’s Oral Histology and Embryology – S.N. Bhaskar – 10th Edition 6. Harper’s Biochemistry – Robert K. Murray – 23rd Edition 7. Fundamentals of Biochemistry – A.C Deb – 6th Edition www.indiandentalacademy.com