BONE

DR. ISHITA SINGHAL

MDS FIRST YEAR
ʘ INTRODUCTION
ʘ CLASSIFICATION OF BONE
ʘ COMPOSITION OF BONES
ʘ BONE HISTOLOGY
ʘ BONE CELLS
ʘ BONE FORMATION
ʘ BONE RESORPTION
ʘ BONE REMODELLING
ʘ ALVEOLAR BONE
ʘ REFERENCES
INDEX
 Bone is a living tissue, which makes up
the body skeleton & is one of the hardest
structures of the animal body.
 It possesses a certain degree of toughness
& elasticity.
 It provides shape & support for the body.
 It provides site of attachment for tendons
& muscles, which are essential for
locomotion.
 It protects the vital organs of the body.
 It serves as a storage site for minerals & INTRODUCTION
provides the medium, the marrow for the
development & storage of blood cells.
 Bones may be classified according to
their :

I. SHAPE

II. DEVELOPMENT

III. MICROSCOPIC STRUCTURE

CLASSIFICATION
 Bones are classified as:

I. LONG

II. SHORT

III. FLAT BASED ON SHAPE

IV. IRREGULAR
 These bones are long & slender like Insert or Drag & Drop
Your Photo
bones of the arms, legs, fingers, toes,
palms of hands & soles of feet.
 They have a tubular diaphysis or the
shaft, which is made of compact bone at
the periphery, surrounding a central
medullary cavity, containing yellow
marrow.
 The two bulky ends of the long bone are
called the epiphysis, which are made of
compact bone at the periphery & spongy
bone at the center. LONG BONE
 The articular surface of the epiphysis is
covered with hyaline cartilage, which
provides a cushioning effect to the
opposing bone ends during joint
movements & absorbs stress.
 These bones are: Insert or Drag & Drop
Your Photo
1. Cube shaped
2. Of nearly equal length & width
3. Consists of spongy bone covered by a
thin layer of compact bone
4. They contain bone marrow, but no
marrow cavity.
 These bones include bones of:
1. Wrist—carpals
2. Ankle—tarsals
SHORT BONE
 These bones are: Insert or Drag & Drop
Your Photo
1. Thin
2. Flat
3. Curved
4. With no marrow cavity
 Spongy bone is present between upper
& lower layer of compact bone.
 Flat bones include bones of:
1. Sternum
2. Ribs
3. Scapula
FLAT BONE
4. Clavicle
5. Bones that form roof of the skull,
parietal, frontal, temporal & occipital
 These bones have complex shapes, Insert or Drag & Drop
Your Photo
notched or with ridges.
 They are made of spongy bone covered
by thin layer of compact bone, with bone
marrow, but no marrow cavity.
 The irregular bones include:
1. Bones of vertebrae
2. Facial bones like ethmoid & sphenoid
3. Pelvic bones like ischium & pubis
4. Calcareous like heel bone
5. Mandible IRREGULAR BONE
6. Maxilla
 Bones are classified as:

I. ENDOCHONDRAL

II. INTRA-MEMBRANOUS
BASED ON
DEVELOPMENT
 Insert or Drag & Drop
 These bones are formed by replacement Your Photo

of hyaline cartilage with bony tissue.

 This type of ossification occurs in bones
of trunk & extremities.

ENDOCHONDRAL
BONES
 Insert or Drag & Drop
 These bones are formed by replacement Your Photo

of sheet like connective tissue

membrane with bony tissue.
 This ossification occurs in the:
1. Cranial & facial flat bones of the skull
2. Mandible
3. Clavicles

INTRA-
MEMBRANOUS
BONES
 Bones are classified as:

I. MATURE BONE

a. Compact Bone
BASED ON
b. Cancellous Bone MICROSCOPIC
STRUCTURE
II. IMMATURE BONE
 Compact bone (cortical bone): Insert or Drag & Drop
Your Photo

It consists of tightly packed osteons or

haversian systems, forming a solid mass.
Since the bone mass is arranged in layers, it
is also called lamellar bone.

 Cancellous bone (spongy bone):

It has a honeycomb appearance, with large
marrow cavities & sheets of trabeculae of
bone in the form of bars & plates.

MATURE BONE
DRY, COMPACT BONE: GROUND, TRANSVERSE SECTION. LOW MAGNIFI CATION.
CANCELLOUS BONE WITH TRABECULAE & BONE MARROW CAVITIES: STERNUM.STAIN: H & E
 Insert or Drag & Drop
 Woven or immature bone is the first Your Photo

formed bone & is temporary with

irregularly oriented collagen fibers of
varying diameters.
 This type of bone is not usually seen
after birth, as the individual ages, it is
replaced by lamellar or mature bone in
postnatal life.
 However it is seen in the alveolar bone &
during healing of fractures.
 Since this bone forms rapidly, it
incorporates many osteocytes.
IMMATURE BONE
IMMATURE BONE
 Bone is a connective tissue composed of:

I. Cells

II. Fibers

III. Ground Substance

 The intercellular substance of bone

consists of: COMPOSITION
I. Organic Substances

II. Inorganic Substances

 The mineral component is composed of
hydroxyapatite crystals, with carbonate
content & low Ca/P ratio than the pure
hydroxyapatite.
 Bone crystals are in the form of thin
plates or leaf-like structures.
 They are packed closely with long axis
nearly parallel to collagen fibrils axis.
 The narrow gaps between the crystals
contain associated water & organic INORGANIC
macromolecules. COMPONENT
 The ions present are calcium phosphate,
hydroxyl & carbonate.
 There are other types of ions also present
in small quantities.
 The organic matrix is known as osteoid &
is made up of:

I. COLLAGEN PROTEIN

II. NON-COLLAGENOUS PROTEIN

ORGANIC
COMPONENT
 Collagen is the major organic component Insert or Drag & Drop
in mineralized bone tissues that contains Your Photo

type I collagen & type V collagen, it

provides the basic structural integrity of
connective tissues.
 The elasticity of collagen imparts
resiliency to the tissue & helps to resist
fractures.
 In woven bone, fibers are interwoven
with a great amount of interfibrillar space
that is occupied by mineral crystals &
associated acidic proteins. COLLAGENOUS
 In mature bone, collagen fibers form
organized sheets, which are oriented
PROTEIN
perpendicular to each other with little
interfibrillar space.
 Alveolar bone contains type I, type III,
type V & type XII collagen (under
mechanical stress).
 Sharpey’s fibers contain type III collagen
with type I collagen.
 Types III & XII collagen fibers are
produced by fibroblasts during the
formation of the periodontal ligament.
 Types I, V & XII collagens are expressed by
osteoblasts.
 The pink to red colour of bone matrix
seen in hematoxylin & eosin sections is
due to the substantial collagen content.
 Non-collagenous proteins comprise the Insert or Drag & Drop
remaining 10% of the total organic Your Photo

content.
 Most are endogenous proteins produced
by bone cells, while some like albumin are
derived from other sources such as blood
& become incorporated into bone matrix
during osteosynthesis.
 Some of the non-collagenous proteins are
Osteocalcin, Osteopontin, Bone NON-
sialoproteins & Osteonectin.
 They also contain variety of growth
COLLAGENOUS
factors. PROTEIN
 The gross appearance of bone consists of
a dense outer compact bone with a
central marrow cavity filled with red or
yellow bone marrow, which is interrupted
by a network of bony trabeculae called
the cancellous bone.

BONE
HISTOLOGY
The osteon is the basic organizational unit
in lamellar bone & is particularly evident in
compact bone. It consists of concentric
lamellae that form a cylinder of bone with
a vascular canal—the haversian canal—at
its center. Numerous osteocytes are
entrapped in these lamellae. These cells
reside in lacunae & their processes in
interconnecting canaliculi that form an
extensive network for the diffusion of
nutrients & the transduction of local bone
status.
Organizational components of bone
 The outer aspect of compact bone is surrounded by a condensed fibro-collagen layer, the
periosteum which has two layers:

I. Outer layer which is a dense, irregular connective tissue termed fibrous layer.

II. Inner osteogenic layer, next to the bone surface consisting of bone cells, their
precursors & a rich vascular supply.

 The periosteum is active during fetal development. It is also important in the repair of
fractures.

 The inner surface of compact & cancellous bone are covered by a thin cellular layer called
endosteum. The main functions of the periosteum & the endosteum are to provide
nutrition for the bone.
 In resting adult bone, quiescent osteoblasts & osteoprogenitor cells are present on the
endosteal surfaces. These cells act as reservoir of new bone forming cells for remodeling
or repair.

 At the periosteal & endosteal surfaces, the lamellae are arranged in parallel layers
surrounding the bony surface & are called circumferential lamellae.

 Deep to the circumferential lamellae, the lamellae are arranged as small concentric layers
around a central vascular canal. Haversian canal & the concentric lamellae together is
known as the osteon or haversian system.

 There may be up to 20 concentric lamellae within each osteon. Osteon is the basic
metabolic unit of bone & it is shaped in the form of a cylinder.
The organization of collagen & the
various lamellae are seen readily using
phase-contrast microscopy (A, B, D).

A: Embryonic (woven) bone is

characterized by randomly oriented
collagen fibrils.
B to F: Collagen fibrils in lamellar
bone assume a layered organization
including circumferential, concentric,
& interstitial lamellae. Interstitial
lamellae are interspersed between
osteons; these represent fragments of
pre-existing concentric lamellae.
Circumferential lamellae enclose the
inner (D) & outer (E, F) aspects of
bone.
 A cement line of mineralized matrix delineates the haversian system. This cement line
contains little or no collagen, & is strongly basophilic, because it has a high content of
glycoproteins & proteoglycans. It marks the limit of bone erosion prior to the formation
of osteon, & is therefore also known as reversal line.

 This line appears to be highly irregular as it is formed by the scalloped outline of the
Howship’s lacunae.

 This line has to be distinguished from the more regular appearance of the resting line,
which denotes the period of rest during the formation of bone.
STRUCTURAL LINES IN BONE
Reversal line or cementing line-
-The site of change from bone resorption
to bone deposition is represented by a
scalloped outline.
-Rich in sialoprotein & osteopontin.

Resting line –
Rhythmic deposition of bone with
periods of relative quiescence seen as
parallel vertical lines.
Appositional growth of
mandible by formation of
circumferential lamellae.
These are replaced by haversian
bone; remnants of
circumferential lamellae in the
depth persisting as interstitial
lamellae.
REVERSAL LINE IN BONE
 The adjacent Haversian canals are connected by Volkmann canals, which also carry small
blood vessels.

 Osteocytes are present in lacunae, at the junctions of the lamellae. Small canaliculi
radiate from lacunae to haversian canal to provide a passage way through the hard
matrix.

 The canaliculi connect all the osteocytes in an osteon together. This connecting system
permits nutrients & wastes to be relayed from one osteocyte to the other.

 The adult bones, between the osteons, contain interstitial lamellae, which are remnants
of osteons, left behind during remodeling.
 Spongy bone & compact bone have the
same cells & intercellular matrix, but
differ in the arrangement of
components.
 Spongy bone looks like a poorly
organized tissue.
 The bony substance consists of large
slender spicules called trabeculae.
 The trabeculae are up to 50 μm thick. SPONGY BONE
 The trabeculae are oriented along lines
of stress to withstand the forces applied
to bone. The marrow spaces are large.
 The trabeculae surround the marrow
spaces from where they derive their
nutrition through diffusion.
 BODY OF THE MANDIBLE
The outer layer of compact bone &
an inner supporting network of
trabecular bone can be distinguished
clearly.
 HEMOPOEITIC TISSUES IN BONES
RED MARROW YELLOW MARROW

It is present in young bone. It is present in old bone.

It is found within cavities of spongy It is seen in epiphysis of long bones.
bone of long bones & diploe of flat
bones.
In newborn infants, the medullary In old bone, the marrow is yellow,
cavity & all areas of spongy bone with loss of hemopoietic potential &
contain red bone marrow. increased accumulation of fat cells.
Red marrow contains stem cells of Yellow marrow of the medullary
both the fibroblast/mesenchymal cavity can revert to red marrow, if a
type & blood cell lineage. person is anaemic & needs increased
red blood cell production.
https://www.youtube.com/watch?v=inqWoakkiTc
 Bone contains many cells like:

I. Osteogenic cells:

a) Osteoprogenitor cells

b) Osteoblasts

c) Bone lining cells

d) Osteocytes
BONE CELLS
II. Osteoclastic cells

a) Osteoclasts
 Osteoprogenitor cells are undifferentiated,
pluripotent stem cells derived from the
connective tissue mesenchyme.
 During bone development, these cells
proliferate by mitosis & express transcription
factors like:
1. Cbfa1/Runx-2
2. Osterix
OSTEO-
to differentiate into osteoblasts, which then PROGENITOR
begin to secrete collagen fibers & the bony
matrix.
CELLS
 They reside in the layer of cells beneath the
osteoblast layer, in the periosteal region, in
the periodontal ligament or in the marrow
spaces.
 Osteoprogenitor cells are divided into two Insert or Drag & Drop
types: Your Photo

1. Determined Osteogenic Precursor

Cells (DOPCs)- Differentiate into
osteoblasts under the influence of
systemic & bone derived growth
factors

2. Inducible Osteogenic Precursor Cells

(IOPCs)- Differentiate into bone
forming cells when stimulated
FORMATION
 Osteoblasts are:
1. Mononucleated cells
2. Derived from osteoprogenitor cells
3. Present on the surfaces of bone
4. Basophilic
5. Plump cuboidal or slightly flattened
cells
 Periosteum also serves as an important
reservoir of osteoblasts, particularly
OSTEOBLASTS
during:
1. Childhood growth
2. After skeletal fractures
3. With bone forming tumors
 LIGHT MICROSCOPIC VIEWS OF EMBRYONIC MANDIBULAR BONE
A: The bone forms by intramembranous ossification & initially assumes a trabecular
organization.
B: Plump-looking osteoblasts line forming bone surfaces.
C: The abundance of large osteocytes entrapped in the bone & the presence of numerous
 Osteoblasts synthesize, secrete, & deposit Insert or Drag & Drop
osteoid. Your Photo

 Osteoid is uncalcified & does not contain

any minerals; however, shortly after its
deposition, it is rapidly mineralized &
becomes hard bone.
 Osteoblasts regulate the mineralization
process of osteoid by releasing matrix
vesicles, which serve as centers for
formation of hydroxyapatite crystals & the
first steps of calcification.
 Further calcification surrounds & embeds
the collagen fibers & the various
glycoproteins.
MORPHOLOGY
OSTEOID
 As osteoblasts have a secretory function,
they have abundant cellular organelles
required for an active protein synthesis.
 The cytoplasm has numerous rough
endoplasmic reticulum which give the cell
a deep basophilic appearance.
 These synthesize procollagen molecules
which are stored in the Golgi complexes
as secretory vesicles.
 Exocytosis of these secretory products
takes place & the molecules are
assembled extracellularly as fibrils to form
the osteoid layer.
 Osteoblasts also secrete cytokines that
regulate cell metabolism.
 They also contain the alkaline
phosphatase enzyme which helps in
creating an alkaline environment for bone
formation.
 The noncollagenous proteins also
participate in regulating mineral
deposition.
 Organic matrix is deposited around the
cell bodies & their cytoplasmic processes
resulting in the formation of canaliculi.
 The cells contact one another by
adherens & gap junctions, to ensure that
osteoblast layer completely covers the
osteoid surface.
 The cytoplasmic processes are not seen in
H & E sections, but in other preparations,
they are in contact with one another &
also with processes of osteocytes in
lacunae beneath them.
 Osteoblasts also contain prominent
bundles of actin, myosin & cytoskeletal
proteins which are associated with
maintenance of cell shape, attachment &
motility.
BONE FORMATION
1. The formation of new bone via synthesis Insert or Drag & Drop
of various proteins & polysaccharides. Your Photo

2. The regulation of bone remodeling &

mineral metabolism.
3. Mineralization of osteoid.
4. Osteocalcin & cbfa-1 are specific to cells
of osteoblast lineage & provide useful
markers of osteoblast phenotype.
5. Osteoblasts also secrete small amounts
of type V collagen, osteonectin,
osteopontin, RANKL, osteoprotegerin,
proteoglycans, latent proteases &
growth factors including bone FUNCTION
morphogenetic proteins.
 FACTORS FAVOURING FORMATION OF OSTEOBLASTS
• LOCAL & SYSTEMIC FACTORS • HORMONES
1. PTH
• BONE MORPHOGENETIC PROTEINS 2. INSULIN
1. BMP-2, BMP-4, BMP-6 3. GROWTH HORMONE
4. VITAMIN D3
• CELL GROWTH FACTORS
1. FIBROBLAST GROWTH FACTORS • TRANSCRIPTION FACTORS
2. INSULIN LIKE GROWTH FACTORS
3. TRANSFORMING LIKE GROWTH FACTORS-BETA • DIFFERENTIATION
4. PLATELET DERIVED GROWTH FACTOR 1. WNT/B-CATWNIN PATHWAY
5. VASCULAR ENDOTHELIAL GROWTH FACTOR 2. CBFA1
3. OSTERIX
• GLUCOCOTICOIDS (IN VITRO)
• REGULATORY
• CYTOKINE-IL 6 1. RUNX-2
 FACTORS LIMITING FORMATION OF OSTEOBLASTS
• TNF α

• PROLONGED TREATMENT WITH GLUCOCORTICOIDS (IN

VIVO)
 Once osteoblasts have completed their Insert or Drag & Drop
function, they are either entrapped in the Your Photo

bone matrix & become osteocytes or

remain on the surface as lining cells.
 Osteoblasts flatten when bone is not
forming & extend along the bone surface.
 These cells contain very few organelles
but, retain gap junctions with osteocytes,
while retaining its vitality.

BONE LINING
CELLS
 But 50–70% of osteoblasts present at the
remodeling site cannot be accounted for
after enumeration of lining cells &
osteocytes.
 It has been proposed that missing
osteoblasts die by apoptosis.
 Tumor necrosis factor (TNF) promotes
apoptosis.
 TGF-β & IL-6 have antiapoptotic effects.
 Glucocorticoids & estrogen withdrawal
promote apoptosis in osteoblasts &
osteocytes.
 MANDIBULAR BONE SOON AFTER BIRTH
By this time the bone has undergone substantial turnover & appears more compact. Bone-
forming surfaces are covered by plump osteoblasts or flattened, less-active cells. Quiescent
areas are covered by bone-lining cells. Osteocytes are present within the calcified matrix & in
some cases within osteoid (asterisks). Osteoclasts usually are found opposite actively forming
 Osteoblasts synthesize & lay down precursors of type I collagen.

Osteoblasts also produce Osteocalcin & the proteoglycans of ground substance & are rich in alkaline phosphatase,
an organic phosphate-splitting enzyme.

The collagen (type I) formed by osteoblasts is deposited in parallel or concentric layers to produce mature bone.

When bone is rapidly formed, as in the fetus or in certain conditions, the collagen is not deposited in a parallel
array but in a basket-like weave & is called woven, immature, or primitive bone.

The main mineral component of bone is an imperfectly crystalline hydroxyapatite [Ca10(PO4)6(OH)2] The mineral
crystals, are deposited along, & in close relation to, the bone collagen fibrils.
 Calcium & phosphorus are derived from the blood plasma & from nutritional
sources

The extracellular matrix of bone is mineralized soon after its

deposition

Very thin layer of unmineralized matrix is seen on the bone surface, & this is called the osteoid layer.

As the process of bone formation progresses, the osteoblasts come to lie in tiny spaces (lacunae) within the
surrounding mineralized matrix & are then called osteocytes.
 Rosenberg Nahum et al (2012) stated that
Bone structural integrity and shape are
maintained by removal of old matrix by
osteoclasts and in-situ synthesis of new bone
by osteoblasts. These cells comprise the
basic multicellular unit (BMU). Bone mass
maintenance is determined by the net
anabolic activity of the BMU, when the
matrix elaboration of the osteoblasts equals
or exceeds the bone resorption by the
osteoclasts. The normal function of the BMU
causes a continuous remodeling process of
the bone, with deposition of bony matrix
(osteoid) along the vectors of the generated
force by gravity and attached muscle activity.

Nahum Rosenberg, Orit Rosenberg and Michael Soudry. Osteoblasts in Bone Physiology—Mini
Review. Rambam Maimonides Med J. 2012 Apr; 3(2): e0013.
 Once the osteoblasts secrete the
extracellular matrix & are entrapped,
they reduce in size & form the
osteocytes.
 The number of osteoblasts that become
osteocytes, depends on the rapidity of
bone formation.
 Embryonic & repair bone, show more
osteocytes, due to rapid formation of OSTEOCYTES
bone.
 There are approximately ten times more
osteocytes than osteoblasts.
 The average half life of human
osteocytes is approximately 25 years.
The death of these leads to resorption of
the matrix by osteoclasts.
A: Light-level micrograph of rat mandibular bone. Osteocytes (Oc), residing in lacunae,
populate the bone. Note the abundant cement lines (CL).
B: Scanning electron microscope view of the extensive “meshwork” of osteocyte cell
 During the preparation of ground
sections, the osteocytes are lost, but the
spaces are filled with debris & appear
black.
 The space in which the osteocytes are
present is called the osteocytic lacuna, &
a thin layer of uncalcified tissue, lines the
lacuna.
 The lacunae can appear ovoid or
flattened.
 Narrow extensions of these lacunae form
channels called canaliculi, in which
osteocytic processes are present.
 Canaliculi do not communicate with
neighbouring systems.
 At the distal end, these processes
contact other osteocytes, osteoblasts &
bone lining cells on the surface through
gap junctions.
 The canaliculi penetrate the bone matrix
& permit diffusion of nutrients, gases &
waste products between osteocytes &
blood vessels.
 Osteocytes also sense the changes in
environment & send signals that affect
response of other cells involved in bone
remodeling.
 This interconnecting system maintains
the bone integrity & bone vitality. Failure
of this leads to sclerosis & death of bone.
 Osteocytes are
‘entrapped’ OSTEOCYTE
osteoblasts within
Numerous &
extensive cell
bone S
processes that
ramify throughout
the bone in Osteocytes occupy
canaliculi & make spaces (lacunae)
contact via gap in bone & are
junctions with defined as cells
processes surrounded by
extending from bone matrix.
other osteocytes or
from osteoblasts or
bone lining cells at
the surface of the
bone Decreased quantity
of synthetic &
secretory organelles
 Transformation of osteoblasts into
osteocytes at the end of bone forming
phase, osteoblasts can have one of four
different fates:
1. Become embedded in the bone as
osteocytes

2. Transform into inactive osteoblasts &

become bone lining cells

3. Undergo apoptosis

4. Transdifferentiate into cells that

deposit chondroid or chondroid bone
 The transformation process is proposed to involve 3 cells:

PREOSTEOBLASTS OSTEOBLASTS OSTEOCYTES

These are less cuboidal in Preosteoblasts differentiate Cells at this early stage of
shape & are located at a into active osteoblasts, osteoblast to osteocyte
distance from the bone which are cuboidal in shape, differentiation are called
surface, & do not deposit & ultimately deposit the large osteocytes.
bone matrix, but can still bone matrix. On mineralization of the
divide. As the bone matrix osteoid, there is a reduction
These cells produce type I deposition continues, in the endoplasmic
collagen which later osteoblasts become reticulum & Golgi apparatus
assemble into collagen embedded in the osteoid. in the osteocyte, suggesting
fibrils after post transitional a decrease in protein
modification. synthesis.
 HOW AN OSTEOBLAST COULD GET TRAPPED WITHIN BONE MATRIX

1 2 3 4
Within one generation, Individual osteoblasts
some osteoblasts slow are polarized, but Osteoblasts of each
down rate of bone those within same generation are
Osteoblasts are
deposition or stop generation are polarized in the same
unpolarised & lay
laying down bone, so polarized differently to direction. One
down bone in all
that they become those in adjacent generation buries the
directions.
trapped by the layers. So bone is preceding one in bone
secretion of their deposited in all matrix.
neighbouring cells. directions.
 DECISION TO TRANSFORM INTO OSTEOCYTE
 During bone formation, processes on the vascular surface of the osteocytes continue to
grow to remain in contact with active osteoblast layer & to modulate their activity.

 When these vascular facing processes stop growing, they produce a signal that induces
the recruitment of these osteoblasts with which they are losing contact.

 The committed osteoblasts are then transformed into osteoblastic osteocytes.

 The signal to stop growing a vascular process, may be issued by the osteoblasts, with
which they have contact or it may be due to the gradual reduction in the vascular supply
to the osteocyte, as new layers of bone are laid down on the osteogenic front.
 Factors that modulate osteoblast
function & in controlling the decision to
transform into an osteocyte are:
1. Runx-2 & osterix -Osteoblast
differentiation

2. Leptin -Protects cells from apoptosis

& facilitates transformation from
osteoblast to pre-osteocyte

3. TGF-β -Increase the propensity of

osteoblast to mature into an
osteocyte & decrease the duration of
its productive functioning by
shortening its life span
 SR Goldring (2015) stated that Osteocytes
are the most abundant cell type in bone and
are distributed throughout the mineralised
bone matrix forming an interconnected
network that ideally positions them to
sense and to respond to local biomechanical
and systemic stimuli to regulate bone
remodelling and adaptation. The adaptive
process is dependent on the coordinated
activity of osteoclasts and osteoblasts that
form a so-called bone multicellular unit that
remodels cortical and trabecular bone
through a process of osteoclast-mediated
bone resorption, followed by a phase of
bone formation mediated by osteoblasts.

Steven R Goldring. The osteocyte: key player in regulating bone turnover. RMD Open. 2015;
1(Suppl 1): e000049.
 Osteoclasts are:
1. Large
2. Multinucleated cells
3. Found along bone surfaces where
resorption, remodeling, & repair of
bone take place
 The osteoclasts originate from the fusion
of blood or hemopoietic progenitor cells
that belong to the mononuclear
macrophage– monocyte cell line of the
red bone marrow. OSTEOCLASTS
 Osteoclasts lie in resorption bays called
Howship’s lacunae.
 RESORPTION &
APPOSITION OF
BONE
Left, Osteoclasts in
Howship’s lacunae.
Right, Osteoblasts
along bone
trabecula. Layer of
osteoid tissue is a
sign of bone
formation.
 Osteoclasts are large cells with 15-20 Insert or Drag & Drop
closely packed nuclei. Your Photo

 Osteoclasts with many nuclei resorb more

bone than osteoclasts with few nuclei.
 These cells are variable in shape due to
their motility.
 The cytoplasm contains microtubules,
which transport vesicles between Golgi
stacks & ruffled membrane.
 Cathepsin containing vesicles & vacuoles
are present close to the ruffled border MORPHOLOGY &
indicating resorptive activity of these
cells. FORMATION
OSTEOCLASTS
 The differentiation into
Hematopoietic osteoclasts is through a Formation of
precursor that can mechanism involving osteoclast requires the
form osteoclasts are cell–cell interaction with presence of
osteoblast stromal cells

Granulocyte
Activated to form bone
Macrophage Colony RANKLigand & M-CSF
resorbing osteoclasts
Forming Unit

These two membrane

Differentiate to form Differentiate & fuse to
Post Mitotic form Immature bound proteins are
Committed Precursor Multinucleated Giant produced by
Cells Cells neighbouring stromal
cells & osteoblasts
RANKL expressed on plasma membrane of stromal & osteoblastic cells bind to
RANK expressed on osteoclastic progenitors to induce a signaling cascade
leading to differentiation & fusion of osteoclast precursor cells.

Osteoclast differentiation & activation is inhibited by osteoprotegerin (OPG),

which is a member of the TNF receptor family & is secreted by osteoblastic
cells.
103
104
105
106
 FACTORS REGULATING OSTEOCLAST FORMATION
• LOCAL & SYSTEMIC FACTORS • HORMONES
1. VITAMIN D3 (TRANSIENTLY AT HIGHER DOSES, IN VIVO)
• HAEMATOPOETIC FACTORS 2. PTH (AT CHRONIC EXPOSURE)
1. M-CSF 3. PGE2 (CHRONIC EXPOSURE & HIGHER
CONCENTRATIONS)
2. GM-CSF
4. GLUCOCOTICOIDS (PHARMACOLOGICAL IN VIVO)

• CYTOKINES
• TRANSCRIPTION FACTORS
1. IL-1
1. NF-kβ
2. IL-6
3. IL-8
4. IL-11
5. TNF-α
 FACTORS LIMITING OSTEOCLAST FORMATION
• DIFFERENTIATION • HORMONES
1. OPG 1. GLUCOCOTICOIDS (PHYSIOLOGICAL CONCENTRATION
IN VITRO)
2. OCIL (OSTEOCLAST INHIBITORY LECTIN)
2. PTH (PHYSIOLOGICAL CONCENTRATION)
3. PGE2 (LOWER CONCENTRATION, SYSTEMIC
• LOCAL OR SYSTEMIC FACTORS
ADMINISTRATION)
4. CALCITONIN
• GROWTH FACTORS
5. ESTROGEN
1. TGF-β
2. IGF-I • CYTOKINES
3. IGF-II
1. IL-4
2. IL-10
• PHARMACOLOGICAL- BISPHOSPHONATES
3. IL-12
4. IL-13
5. IL-18
6. IFN-γ
 Charles JF et al (2014) discovered the clinical
application of anti-resorptive agents, and
these have prevented countless fractures
and improved the quality of life of patients
with bone cancer.

Charles JF and Aliprantis AO. Osteoclasts: more than ‘bone eaters’. Trends Mol Med. 2014 Aug;
20(8): 449–459.
 The process of bone formation is called
osteogenesis.
 Bone formation occurs by 2 main
mechanisms:

I. Intramembranous

II. Endochondral
BONE
FORMATION
 It is the direct formation of bone within
highly vascular sheets of condensed
primitive mesenchyme.
 This process occurs in the flat bones of
the skull & clavicles.
 It begins approximately towards the end
of second month of gestation.
INTRA-
 The mechanism of intramembranous
ossification involves: MEMBRANOUS
1. BMPs activate cbfa1 gene in
mesenchymal cells.
OSSIFICATION
2. The cbfa1 transcription factor
transforms mesenchymal cells into
osteoblasts.
 At the site where the bone will develop  loose mesenchymal cells
(widely separated, pale staining, stellate shaped with interconnecting cytoplasmic processes)

Capillaries grow into mesenchyme  center of osteogenesis develops

Mesenchymal cells round, basophilic with thick interconnecting cytoplasmic processes

Differentiate into osteoblasts  secrete organic matrix called osteoid

 osteoblasts get entrapped into the bone matrix  osteocytes

Calcification of matrix takes place

INTRAMEMBRANOUS BONE FORMATION
Light micrographs of intramembranous bone
formation in the rat calvaria.

A: Ectomesenchymal cells (asterisks)

condense between the skin and developing
brain.

B: These cells differentiate into osteoblasts

that deposit bone directly as woven
cancellous bone.
 Intramembranous bone formation around
the cartilage model of digits
A and B: Cross section.
C: Longitudinal section.
The preparations are stained for alkaline
phosphatase activity, seen here in blue. Such
activity is present in the perichondrium and
periosteum, as well as in areas of vascular
invasion.
 WOVEN BONE LAMELLAR BONE

 Immature bone  Mature bone

 Intertwined collagen fibers oriented in many directions  Collagen fibers are orderly arranged in right angles

 Interfibrillar space is more  Interfibrillar space is less

 Hematoxyphillic matrix  Eosinophillic matrix

 Formation & mineralization is faster  Formation & mineralization is slower

 Mineral density is lower  Mineral density is higher

 Water content is higher  Water content is lower

 Woven bone can be completely removed by osteoclasts  Osteoclasts can remove portions of lamellar bone at a

 Enriched in Bone Acidic Glycoprotein 75 & Bone time

Sialoprotein  Enriched in Osteocalcin

 It is also called Intracartilaginous
ossification.
 This type of ossification involves the
replacement of a cartilaginous model by
bone.
 It occurs at the extremities of all long
bones, vertebrae, ribs, articular
extremity of the mandible & base of the
ENDRO-
skull. CHONDRAL
OSSIFICATION
 At the site where the bone will develop  condensation of mesenchymal cells  in avascular condition 
chondroblast lay down cartilage matrix  surrounded by perichondrium  followed by mineralization of matrix

Increase in length  interstitial growth

Increase in thickness  appositional growth

In the middle of diaphysis  capillaries grow into the perichondrium  perichondrium is referred to as
periosteum

Cells in the inner layer of perichondrium  differentiate into osteoblasts thin collar of bone matrix formed
 around mid region of model

Chondrocytes grow  secrete alkaline phosphatase  calcification of matrix  eventually blood supply cut off 
no nutrient  death of chondrocytes  cavitation of cartilage matrix
 Periosteal capillaries & osteogenic cells invade mid region of model
 development of primary ossification centre

Osteogenic cells in periosteal bud  differentiate into osteoblasts

 deposit bone matrix on residual calcified cartilage

Osteoclasts break down newly formed spongy bone  formation of medullary cavity
At this stage  2 ends of developing bone  composed of cartilage (epiphysis)

Formation of bone same as in primary ossification centre  no medullary cavity formation in epiphysis  hyaline
cartilage at two places, i.e. on articular surface & at junction of the epiphysis & diaphysis (epiphyseal plate)
ENDOCHONDRAL BONE GROWTH
A to C: Light micrographs of
Endochondral ossification in the rat
tibia. Sections were stained with
von Kossa's stain for revealing
mineral (in black).

C: shows at higher magnification

the transition between the
maturation and calcification zones
of the growth plate cartilage.
https://www.youtube.com/watch?v=xXgZap0AvL0
 Bone resorption is the removal of mineral Insert or Drag & Drop
& organic components of extracellular Your Photo

matrix of bone under the action of

osteolytic cells, of which the most
important is the osteoclast.

BONE
RESORPTION
Formation of osteoclast progenitors in hematopoietic tissues vascular dissemination generation of resting pre-
osteoclasts & osteoclasts in bone  activation of osteoclast

Interaction of RANKL & RANK  migration to osteoclasts to resorption site

Matrix-Metallo Proteinase 9 helps in migration  RANKL increases osteoclast formation

Formation of ruffled border & sealing zone  attachment of plasma membrane of osteoclasts to bone matrix
through integrin αVβ3  MMP 13 secreted osteoblast degrades osteoid & expose sites for osteoclast attachment

Osteoclasts synthesize  cytoplasmic carbonic anhydrase II  protons released in ruffled border

 low pH due to secretory activity of HCl  dissolution of hydroxyapatite

Enzymes like Cathepsin K & MMP-9 synthesized in RER  transported in Golgi complex 
moved to ruffled border in vesicles  contents released into extracellular lysosomes
 degradation of organic matrix
 Removal of degradation proteins
 free organic & inorganic particles endocytosed from lacunae across ruffled border into osteoclasts

Packed in free membrane bound vesicles  released by exocytosis

TRAP ( Tartrate Resistant Acid Phosphatase) helps in migration of osteoclast to adjacent site

Following resorption, osteoclasts undergo apoptosis, which

provides a mechanism for limiting resorptive activity.
129
130
131
132
134
136
137
https://www.youtube.com/watch?v=GpMV197xZXc
 RESORBED SURFACE UNRESORBED SURFACE

It is scalloped & it exhibits scattered

Osteoblasts line the bone surface
osteoclasts

Osteoclasts lie in Howship's lacunae Osteoblasts are present on the bone

or resorption bay
surface

The side of the osteoclast cell Osteoblast is a mononucleated cell on

adjacent to bone contains few nuclei the bone surface.
than the opposite side.
 Bone remodeling is performed by clusters Insert or Drag & Drop
of bone resorbing osteoclasts and bone Your Photo

forming osteoblasts arranged within

temporary anatomical structures known
as Basic Multicellular Units (BMUs).
 Traversing and encasing the BMU is a
canopy of cells that creates a bone-
remodeling compartment (BRC).
 The main functions of remodeling are to
prevent the accumulation of damaged BONE
and fatigued bone by regenerating new
bone, allow the bone to respond to
REMODELLING
changes in mechanical forces and to
facilitate mineral homeostasis.
 ACTIVATION PHASE detection of signal in form of mechanical strain/ hormonal action
 recruitment of monocyte-macrophage osteoclast precursor
 interaction of osteoclast and osteoblast precursor cells

RANKL acts on osteoblast and RANK acts on osteoclasts

 differentiation, migration and fusion of large multinucleated osteoblasts

RESORPTION PHASE  osteoclasts dissolve minerals followed by release of TGF, PDGF, IGF ( I and II)
 scalloped Howship’s lacunae formed  mononuclear cells  macrophages remove collagen remnants

REVERSAL PHASE  resorption cavities contain preosteoblasts  apoptosis of osteoclasts  new bone formation
on reversal line under influence of released TGF, PDGF, IGF I and II in resorption phase

MINERALISATION PHASE  incorporation of hydroxyapatite

https://www.youtube.com/watch?v=0dV1Bwe2v6c
 It includes:

I. Hormones:

a. Parathyroid hormone

b. Calcitonin MEDIATORS OF
BONE
II. Vitamin D metabolites:
REMODELLING
a. Estrogen receptors

b. Growth hormones

c. Glucocorticoids
 PTH is produced in the parathyroid glands
in response to hypocalcemia, stimulating
bone resorption.
 A stimulating role in bone formation has
also been established through the
synthesis of IGF 1 and TGF β.
 This dual effect of resorption and
formation is explained by the fact that the PARATHYROID
continuous supply of PTH stimulates bone
resorption through the synthesis of
HORMONE
RANKL on the part of the osteoblastic
cells, while at intermittent doses, it would
stimulate the formation of bone,
associated with an increase of the growth
factors and with a decrease in the
apoptosis of osteoblasts.
 Calcitonin is secreted when blood calcium
levels rise.
 It inhibits bone resorption and promotes
calcium salt deposition in bone matrix,
effectively reducing blood calcium levels.
 As blood calcium levels fall, calcitonin
release wanes as well.
 Calcitonin also reduces the number and
activity of osteoclasts. CALCITONIN
 The major active metabolite of vitamin D
is 1,25-dihydroxycholecalciferol.
 This has been shown to affect bone
formation and also to cause bone
resorption.
 Its effect on bone resorption appears to
be by the differentiation of committed
progenitor cells into mature cells.
 It favors the intestinal absorption of VITAMIN D
calcium and phosphate and therefore
bone mineralization.
 It is necessary for normal growth of the
skeleton.
 They are present on osteoblasts,
osteocytes and osteoclasts.
 They favor bone formation, increasing the
number and function of osteoblasts.
 It has also been proposed that these
hormones are believed to increase the
levels of OPG, which inhibits resorption.
ESTROGEN
RECEPTORS
 They act directly on the osteoblasts
stimulating their activity and increasing
the synthesis of collagen, Osteocalcin and
alkaline phosphatase.
 Indirect action is produced through an
increase in the synthesis of IGF-I and II by
osteoblasts, which stimulate the
proliferation and differentiation of GROWTH
osteoblasts.
HORMONES
 Glucocorticoids at high doses inhibit the
synthesis of IGF-1 by osteoblasts and
suppress BMP-2 and Cbfa-1 which are
essential for the formation of osteoblasts.
 But, at physiological doses they are
believed to have osteogenic capacity
favouring osteoblastic differentiation.

GLUCOCORTICOIDS
 IL-1 inhibits the apoptosis of osteoclasts.
 TNF inhibits bone collagen and
noncollagenous protein synthesis.
 Prostaglandins are local pathological
mediators of bone destruction, like in
inflammation.
 IGF-I and II mediate osteoblast–
osteoclast interaction and participate in
bone remodeling. LOCAL FACTORS
 BMPs participate in the formation of
bone and cartilage. They are the most
important factors for osteoblast
differentiation.
 PDGF stimulates protein synthesis by
osteoblasts and also favors bone
resorption.
 Bacterial products such as
lipopolysaccharide, capsular material,
lipoteichoic acids and peptidoglycans
may act as foreign antigens and induce
monocytes, macrophages and then bone
cells to produce prostaglandins and
cytokines such as IL-1, leading to bone
resorption.
 Mechanical factors: Under muscular
action, tension is transmitted to the
bone, which is detected by osteocyte
network. These osteocytes produce
prostaglandins and IGF-1 which stimulate
osteoblast activity leading to increased
bone formation. Absence of muscular
activity accelerates resorption.
 The markers of bone formation are
(Serum markers):
1. Alkaline phosphatase (total)

2. Alkaline phosphatase (skeletal

isoenzymes)
MARKERS
3. Osteocalcin
OF BONE
4. Procollagen I extension peptide TURNOVER
 The markers of bone resorption are (Urinary
markers):
1. Urine calcium

2. Urinary hydroxy proline

3. Collagen crosslink fragments

4. Urine n-telopeptide

5. Urine c-telopeptide

6. Urine total pyridinoline

 FACTORS REGULATING BONE REMODELLING
LOCAL FACTORS SYSTEMIC FACTORS
• GROWTH FACTORS • HORMONES
1. IGF I & II 1. DECREASE BONE RESORPTION
2. TGF β • CALCITONIN
• ESTROGEN
3. FGF
2. INCREASE BONE RESORPTION
4. PGDF
• PTH
• GLUCOCORTICOIDS
• CYTOKINES • VITAMIN D (HIGH DOSE)
1. IL-1 3. INCREASE BONE FORMATION
2. IL-6 • GROWTH HORMONE
3. IL-11 • VITAMIN D
• INSULIN
4. PGE2
• LOW DOSE PTH
4. DECREASE BONE FORMATION
• GLUCOCORTICOIDS
 The alveolar process is defined as that Insert or Drag & Drop
part of the maxilla and the mandible that Your Photo

forms and supports the sockets of the

teeth.

ALVEOLAR
BONE
1. Houses the roots of teeth.
2. Helps to move the teeth for better
occlusion.
3. Helps to absorb and distribute occlusal
forces generated during tooth contact.
4. Supplies vessels to periodontal ligament.
5. Houses and protects developing
permanent teeth, while
primary teeth.
supporting
FUNCTIONS
6. Organizes eruption of primary and
permanent teeth.
 Near the end of the second month of fetal
life, the maxilla as well as the mandible
form a groove that is open towards the
surface of the oral cavity.
 Tooth germs develop within the bony
structures at late bell stage.
 Bony septa and bony bridge begin to form DEVELOPMENT
and separate the individual tooth germs
from one another. OF ALVEOLAR
 At this stage, dental follicle surrounds each
tooth germ.
PROCESS
 Even prior to root formation, tooth germs
within bony compartments show bodily
movement in various directions to adjust to
growing jaws, causing bone remodeling of
bony compartment.
 The alveolar process forms with the
development and the eruption of teeth, and
it gradually diminishes in height after the
loss of teeth.
 As roots develop, the alveolar process
increases in height.
 Also, the cells in the dental follicle start to
differentiate into periodontal ligament and
cementum.
 At the same time, some cells in the dental
follicle differentiate into osteoblasts and
form alveolar bone proper.
 Development of mandibular symphysis and formation of bony septa between developing teeth.
A: Newborn infant. Symphysis wide open. B: Child 9 months of age. Symphysis partly closed.
 The alveolar bone proper consists partly
of lamellated and partly of bundle bone
and is about 0.1–0.4 mm thick.
 It surrounds the root of the tooth and
gives attachment to principal fibers of the
periodontal ligament.

ALVEOLAR BONE
PROPER
SECTION THROUGH JAW SHOWING NUTRIENT
CANAL OF ZUCKERKANDL AND HIRSCHFELD IN
INTERDENTAL BONY SEPTUM
 The supporting alveolar bone consists of
two parts:
1. Cortical plates
2. Spongy bone
3. Crest of the alveolar septa

PARTS OF
ALVEOLAR BONE
 Cortical plates consist of compact bone
and form the outer and inner plates of
the alveolar processes.
 They are thickest in the premolar and
molar region of the lower jaw, especially
on the buccal side.
 In the region of the anterior teeth of both
jaws, the supporting bone usually is very
thin.
CORTICAL PLATES
Proportion of cancellous bone and compact bone in the anterior region
Proportion of cancellous bone and compact bone in the posterior region
 Spongy bone fills the area between the
cortical plates and the alveolar bone
proper.
 It contains trabeculae of lamellar bone.
 These are surrounded by marrow that is
rich in adipocytes and pluripotent
mesenchymal cells.
 The trabeculae contain osteocytes in the
interior and osteoblasts or osteoclasts on SPONGY BONE
the surface.
 These trabeculae of the spongy bone
buttress the functional forces to which
alveolar bone proper is exposed.
The study of radiographs permits the classification of the spongiosa of the alveolar process into
two main types:

Type I - The interdental and interradicular Type II shows irregularly arranged,

trabeculae are regular and horizontal in a numerous, delicate interdental and
ladder like arrangement. interradicular trabeculae.
 The shape of the outlines of the crest of
the alveolar septa in the radiograph is
dependent on the position of the
adjacent teeth.
 If the neighboring teeth are inclined, the
alveolar crest is oblique.
 In the majority of individuals the
inclination is most pronounced in the CREST OF THE
premolar and molar regions, with the
teeth being tipped mesially.
ALVEOLAR SEPTA
 Then the cementoenamel junction of the
mesial tooth is situated in a more occlusal
plane than that of the distal tooth, and
the alveolar crest therefore slopes distally.
Diagram showing relation between cementoenamel junction of adjacent teeth and shape of
crests of alveolar septa
 In older individuals:

1. Alveolar sockets appear jagged and

uneven.
2. The marrow spaces have fatty
infiltration.
3. The alveolar process in edentulous jaws
decreases in size.
4. Loss of maxillary bone is accompanied
by increase in size of the maxillary sinus. AGE CHANGES
5. Internal trabecular arrangement is more
open, which indicates bone loss.
6. The distance between the crest of the
alveolar bone and CEJ increases with
age—approximately by 2.81 mm.
 Due to continuous eruption of teeth called
physiological mesial drift, alveolar bone
undergoes internal reconstruction; bone
forms on the distal side and resorbs on the
mesial side.
 This plasticity of bone enables orthodontic
movement possible. Bone is resorbed on
the side of pressure and deposited on the
side of tension. CLINICAL
 In the healing of fractures, a bony callus is
formed which is an embryonic type of bone CONSIDERATIONS
with less amounts of calcified intercellular
substance.
 Resorption after tooth loss is downward and
outward in the mandible, but in the maxilla
it is upwards and inwards.
A: THE LAMINA DURA (ARROWS) APPEARS AS A THIN OPAQUE LAYER AROUND TEETH AND
B: AROUND A RECENT EXTRACTION SOCKET.
 Traditional treatment methods for
promoting bone healing primarily utilize
bone grafts or synthetic materials to fill the
defects and provide structural support.
 Bone grafting to stimulate bone deposition
has been used in periodontal surgery since
the 1970s.
 It involves a surgical procedure to place
bone or bone substitute material into a THERAPEUTIC
bone defect with the objective of producing
new bone and possibly the regeneration of CONSIDERATIONS
periodontal ligament and cementum.
 Bone grafts can be of 3 types:

AUTOGRAFTS ALLOGRAFTS XENOGRAFTS

It utilize the patient’s bone, They are obtained from Xenografts are obtained
which can be obtained from another human source, from animal sources; usually
intraoral or extraoral sites. typically highly processed cows and/or pigs. They
They are the best materials bone powder from human include processed animal
for bone grafting, are very cadavers. The age and bone or growth proteins.
well accepted by the body health of the donor can Again, the risk of disease
and may produce the fastest affect the rate of bone transmission and/or
rate of bone growth. With regeneration. The risk of rejection is reduced by
autografts, the patient is disease transmission and/or processing.
assured of protection from rejection is handled by
disease transmission and/or processing and quality
immune reaction. control.
 Zeeshan Sheikh et al (2017) commented on
how to overcome complications related to
the epithelial down-growth and/or collapse
of the non-rigid barrier membrane and how
to maintain space, clinicians commonly use
a combination of membranes with hard
tissue grafts. He has stated various available
natural tissues and biomaterial-based bone
replacement graft and membrane options
used in periodontal regeneration
applications.

Zeeshan Sheikh, Nader Hamdan, Yuichi Ikeda, Marc Grynpas, Bernhard Ganss, and Michael
Glogauer. Natural graft tissues and synthetic biomaterials for periodontal and alveolar bone
reconstructive applications: a review. Biomater Res. 2017; 21: 9.
AUTOGRAFTS
ALLOGRAFTS
XENOGRAFTS
 It includes natural and synthetic
hydroxyapatites, ceramics, calcium
carbonate, silicon-containing glasses, and
synthetic polymers.
 Synthetic materials carry no risk of
disease transmission or immune system
rejection. They help create an SYNTHETIC BONE
environment that facilitates the body’s
regenerative process. GRAFTING
 A guided tissue regeneration approach
has evolved which is an epithelial
MATERIALS
exclusionary technique, which facilitates
the cells of the periodontal ligament to
differentiate into osteoblasts,
cementoblasts and fibroblasts resulting in
regeneration of the lost periodontium.
 It include materials, such as enamel
matrix proteins, that can be premixed
with vehicle solution.
 They are intended as an adjunct to
periodontal surgery for topical application
onto exposed root surfaces or bone to
treat intrabony defects and furcations due
BIOLOGICALLY
to moderate or severe periodontitis. MEDIATED
 Enamel matrix protein leave only a
resorbable protein matrix on the root
STRATEGIES
surface, which makes bone more likely to
regenerate.
 These bone morphogenetic proteins help
to initiate a cascade of events leading to
the differentiation of progenitor cells into
phenotypes involved in periodontal
regeneration.
 REFERENCES
TEN CATE’S ORAL HISTOLOGY 9TH EDITION
ORBAN’S ORAL HISTOLOGY AND EMBRYOLOGY 14TH EDITION
RAJKUMAR’S TEXTBOOK OF ORAL ANATOMY, HISTOLOGY, PHYSIOLOGY AND TOOTH
MORPHOLOGY 2ND EDITION
Nahum Rosenberg, Orit Rosenberg, and Michael Soudry. Osteoblasts in Bone Physiology
—Mini Review. Rambam Maimonides Med J. 2012 Apr; 3(2): e0013.
Steven R Goldring. The osteocyte: key player in regulating bone turnover. RMD Open.
2015; 1(Suppl 1): e000049.
Charles JF and Aliprantis AO. Osteoclasts: more than ‘bone eaters’. Trends Mol Med. 2014
Aug; 20(8): 449–459.
Zeeshan Sheikh, Nader Hamdan, Yuichi Ikeda, Marc Grynpas, Bernhard Ganss, and
Michael Glogauer. Natural graft tissues and synthetic biomaterials for periodontal and
alveolar bone reconstructive applications: a review. Biomater Res. 2017; 21: 9.