Bone development and morphology / dental crown & bridge courses

BONE
Development and
Morphology
INDIAN DENTAL ACADEMY
Leader in Continuing Dental Education
www.indiandentalacademy.com

CONTENTS
• Introduction
• Functions of bone
• Division of skeletal system
• Classification of bone
• Structural anatomy of long bones
• Composition of bone
• Bone development

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.

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.

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.

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

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

FACIAL BONES
Nasal Bone 2
Maxillae 2
Zygomatic Bones 2
Mandible 1
Lacrimal Bones 2
Palatine Bones 2
Inferior Nasal Conchae 2
Vomer 1

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).

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).

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.

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.

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).

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.

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

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.

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.

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.

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

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.

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.

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.

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%

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

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.

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.

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.

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

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.

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.

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

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.

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.

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.

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.

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.

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

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.

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.

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.

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

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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