OSSA

DR. YAN EFFENDI HASJIM, DAHK

2014

FUNCTION OF BONE
1. FISICAL AND MECHANICAL FUNCTIONS
GREAT STRENGTH & HARDNESS

ORGANISATION

STRUKTURE AND

(1)

2. METABOLIC AND HOMEOSTATIC FUNCTIONS

QUITE RESPONSIVE TO MERTABOLIC,
(MOBILIZABLE Ca, HOMEOSTATIC IMPORTANT IONS)
CONTINOUS RENEWED AND RECONSTRUTIZED THROUHOUT THE LIFE
TIME
CONTINOUS INTERNAL REORGANIZATION AND RESPONSIVENESS TO
EXTERNAL MECHANICAL FORCE
DYNAMIC LIVING MATERIAL

RESORPTION,

REMODELING, RECOVERY (2)

3. HEMOPHOETIC FUNCTIONS

BONE MARROW (3)

BONE = HARDNESS, STRENGLY AND

DYNAMIC TISSUE

1.
2.
3.
4.

5.
6.
7.
8.

ORGANIZATION
HISTOFISIOLOGY OF BONE
MICROSTRUCTURE
OSTOGENESIS, GROWTH AND
DEVELOPMENT
RESORPTION OF BONE
REMODELING OF BONE
REPAIR OF BONE
DISEASES OF BONE

1. ORGANIZATION
A LONG BONE

EPHYPISE, DIAPHYSE,
METHAPHYSE PLAT
(GROWTH)

PARS COMPACTA, PARS

SPONGIOSA /CALCANEOUS

PERIOSTEUM, ENDOSTEUM

CAVUM MEDULLARE

CARTILAGE ARTICULATION

OSTEOGENESIS
ENCHONDRALES

A FLAT BONE OF THE SKULL (SKULL

CAP)

INNER & OUTER TABLES, (COMPACT

BONES),

MIDLE THICK LAYER , DIPLO (SPONGY

BONE), LABYRINTH MADULLARE

OSTEOGENESIS INTRAMEMBRNOUS

2. HISTOFISIOLOGY OF BONE

HOMEOSTATIC, MAINTENANCE BLOOD LEVEL OF Ca

(RESORPTION & DEPOSITION MATRIX)

CONTINOUS RENEWED AND RECONSTRUTIZED THROUHOUT

THE LIFE TIME (INTERNAL REMODELING)

CONTINOUS INTERNAL REORGANIZATION AND

RESPONSIVENESS TO EXTERNAL MECHANICAL FORCE
(ANATOMICAL REMODELING)
HEMOPHOETIC (CAVUM MEDULLARE)

MICROSTRUCTURE
COMPACT BONE

SOLID CONTINOUS MASS, VERY

DENCE
LAMELLA SYSTEM
LAMELLA SYSTEM
OSTEON UNITE / HAVERS SYSTEM
LAMELLA SIRCUFERENCIAL
LAMELLA INTERSTIRTIAL

LAMELLA CONCENTRIC
(CYLINDERS)
OSTEON UNITE / HAVERS
SYSTEM

CEMENTING LINE

BONE MATRIX

ORGANIC COMPONENT
COLLEGENS FIBERS
LAMELLA
GROUND SUBSTANCE

ANORGANIC COMPONENT

OSTEONS
HAVERSIAN UNIT

COMPOSITION:
1. CYLINDERS OF LAMELLAE
(CONCENTRICCALLY),
2. OSTEOCYTES IN LACUNAE
3. HAVERSIAN CANAL (NEUROVASCULAR IN CONNECTIVE TISUUE)

LAMELLA CONCENTRIC;
. COLLAGEN TYPE I,. HELICAL
ARRANGEMENT AROUND THE
HAVERSIAN CANAL
. THIN CEMENTING LINE

HAVERSIAN CANAL,
. OSTEOBLAST AND OSTEOPROGENITOR,
. (NEURO-VASCULAR IN CONNECTIVE
TISUUE)

MICROSCOPIC STRUCTURE
OF COMPACT BONE

HAVERSIAN CANAL (CONNECTIVE

TISSUE, VASCULAR, NERVE, LYMPH)

CONCENTRIC LAMELLA ( COLLAGEN

FIBERS)

OSTEOCYTES IN LACUNAE, PROCESSUS

IN INTERCELLULAR CANALICULI

THIN CEMENT

INTERSTITIAL LAMELLA

SPONGI/CANCELLOUS BONE

POROUS BONE,

BRANCHING BONY SPICULES/TRABECULAE,

LABYRIN (BONE MARROW)

MATRIX OF BONE
1. COLLAGENFIBERS
COLLAGEN I TYPE, (95%)
HELICAL ARRANGEMENT AROUND THE HAVERSIAN CANAL

2. GROUND SUBSTANCE, MATRIX (ORGANIC) CALCIFIED

ONLY 5%, IMPORTANT IN BONE METABOLISM AND
MINERALIZATION
FILLS SPACE BETWEEN CELLS AND FIBERS, LUBRICANT &
BARRIER
MAINLY 2 CLASSES COMPONENT:
1).GLYCOSAMINOGLICANS
2).STRUCTURAL GLYCOPROTEINS

CALCIFIED, >> CALSIUM PHOSPHATE (CRYSTALS) HARDNESS

OSEOMUCOID: (DURING OSTEOGENESIS) NONCALCIFIED

2. SPECIFIC BONE
GLYCOPROTEIN
(NONCOLLAGENUS

BONE OSTEOCALCIN, GLA PROTEIN, VIT K DEPENDENT (BINDS

PROTEIN,
TO HYDROXYAPATITE),

BONE SIALOPROTEIN, HAS BINDING SITES FOR MATRIX

COMPONENTS AND INTEGRINS, (SUGESTING ITS INVOLVEMENT IN
ADHERENCE OF THESE CELLS TO MATRIXS).

OSTEOCALCIN AND SIALOPROTEIN, BOTH BIND CALCIUM AVIDLY

AND MAY BE RESPONSIBLE FOR PROMOTING CALCIFICATION
BONE MATRIX

OSTEOPONTIN (ALSO BINDS TO HYDROXYAPATITE, BUT HAS

ADDITIONAL BINDING SITE FOR OTHER COMPONENTS, FOR
INTEGRINS (OSTEOBLASTS AND OSTEOCLASTS).

BONE MORPHOGENIC PROTEIN

BONE PROTEOLIPID

BONE PHOSPHOPROTEIN

OSTEONECTINE

BONE PROTEOGLYCAN

VITAMIN D STIMULATES THE SYNTHESIS OF THESE

GLYCOPROTEINS

1. GLYCOSAMINOGLYCAN

SULFAT GLYCOSAMINOGLYCANS (CHONDROITIN 4-SULFAT,

CHONDROITIN 6-SULFAT, KERATAN SULFAT), WITH PAS REAGENT,
SLIGHT METACHROMASIA

NONSULFAT GLICOSAMINOGLICAN (HYALURONIC ACID, ONLY)

PROTEOGLYCAN:
FORMATION AND COMPOSITION
SULFATED GLYCOSAMINOGLICANS
(CHONDROITIN SULFATE) WITH PROTEIN
CORES FORM SMALL PROTEOGLYCAN
MOLECULES
LINGKING PROTEIN , BIND THE
PROTEIN CORE TO THE LINEAR
HYALURONIC ACID MOLECULES FORM
VERY LARGE AGGRECAN COMPOSITES
(AGGREGATED PROTEOGLYCANS
MOLECULE).
CHONDROITIN SULFAT , BIND TO
COLLAGEN FIBERS FORMING CROSS-

CELLS OF BONE
CELLS OF BONE
1) OSTEOPROGENITOR CELLS, (OSTEOGENIC)
IN CELLULAR LAYER OF PERIOSTEUM
2) OSTEOBLAST, (SECRETE MATRIX), CELLULAR
LAYER OF PERIOSTEUM, IN HAVERS CANALS
3) OSTEOCYTES, (MATURE/INACTIVE), IN
LACUNA , CALCIFIED MATRIX.
4) OSTEOCLAST, (RESORBS MATRIX , BONE
RESORPTION AND REMODELING)

1. OSTEOPROGENITOR CELLS

DRIVED EMBRYONIC MESSENCHYMAL

CELLS,

POTEN TO DIFFERENTIATE INTO

OSTEOBLAST
MOST ACTIVE DURING PERIOD BONE
GROWTH

Osteoprogentor cell:
Stem cell whose
divisions produce osteoblast

DIFFERENTE INTO CHONDEROGENIC CELLS

(UNDER LOW OXYGEN TENSION , REPAIR
BONE)
BECOME INTO OSTEOBLAST , UNDER
INFLUENCE BONE MORPHOGENIC PROTEIN
(BMP) FAMILY AND TRANSFORMING
GROWTH FACTOR (TGF )

LOCATION : INNER CELLULAR LAYER OF

PERIOSTEUM, LINNING HAVERSIAN CANAL ,
ENDOSTEUM .

SPIDLE SHAPED, PALE STAINING OVAL

NUCLEUS; PALE CYTOPLASMA, SPARSE RER,
POORLY DEVELOPED GOLGI APPARATUS

2. OSTEOBLASTS

LOCATION: ON SURFACE OF BONE IN

PERIOSTEUM (CELLULAR LAYER), IN
HAVERS CANALS (GROWTH BONE/REPAIR
BONE)

SYNTHESIZE ORGANIC MATRIX

Immature bone cell that

secretes organic
component of matrix

intramembranous ossification
OSTEOBLAST (Ob) line the bony
spicule, secreting osteoid onto
the bone.
OSTEOCLAST (Oc), housed in
Howship's lacunae.

ACTIVELY, BASOPHYLIC CYTOPLASM

SECRETORY GRANULES (MATRIX

PRECURSORS), PAS REAGEN
VESICLES STAIN PINK.

CYTOPLASM PROCESSES

SHORT PROCESSES, NEIGHBORING

OSTEOBLAST, LONG PROCESSES
OSTEOCYT.

FORM GAP-JUNCTIONS

CONTROLE OSTREOCLAST IN BONE

RESORPTION (REMODELING,REPAIR BONE),
SECRETE
1. OSTEOPROTEGERIN LIGAND (OPGL),

BY INTEGRIN & PTH STIMULATES

SECRETE OPGL

OPGL INDUCES DIFFERENSTIATION OF

PREOSTEOCLATS , AND IT INCREASE
RANKL EXRESSION.

2. OSTEOCLAST-STIMULATING FACTOR (OSF)

ACTIVATE OSTEOCLASTS TO RESORB BONE
3. ENZYMES REMOVING OSTEOID
OSTEOCLASTS CAN MAKE CONTACT WITH
MINERALIZED BONE SURFACE

SYNTHESE ORGANIC MATRIX (COLLAGEN

I, PROTEOGLYCANS, GLYCOPROTEINS)

CLINICAL CORRELATIONS
MONITOR BONE FORMATION

OSTEOBLAST CELLS MEMBRANES, >> ENZYME ALKALINE

PHOSPHATASE.

DURING ACTIVE BONE FORMATION, SECRETE HIGH LEVEL

(ELEVATING LEVEL IN THE BLOOD).

MONITOR BONE FORMATION (REPAIR BONE) MEASURING

THE BLOOD ALKALINE PHOSPHATASE LEVEL.

3. OSTEOCYTES

Osteocytes trapped in
calcified matrix, in
lacuna

IN LACUNA, NO CONTAC TO CALCIFIED MATRIX

(OSTEOID BUMFER),

MATURE-INACTIVE CELLS, (BUT SECRETE

SUBSTANCES FOR BONE MAINTENANCE)

PROCESSES IN CANALICULI
GAP-JUNGTION TO NEIGBORING
OSTEOCYTES AND OSTEOBLAST.
EXTRACELLULAR FLUID NUTRIENS AND
METABOLITS

REMODELING: MECHANOTRANSDUCTION,
STIMULATE TO RELEASING
CYCLIC ADENOSINE MONOPHOSPHATE
(cAMP),
OSTEOCALCIN-LIKE GROWTH FACTOR ,
INSULIN-LIKE GROWTH FACTOR,
FACILITATES THE REQRUITMENT OF
PREOSTEOBLAST TO ASSIST IN THE

4. OSTEOCLAST

RESORBING BONE DIE (APOPTOSIS).

(GROWTH, REMODWLING, REPAIR BONE)

RECEPTOR :
OSTEOCLAST-STIMULATING FACTOR
(OSTEOBLAST) AVCTIVE RESORB
OSTEOPROTEGERIN (OPG)
(OSTEOBLAST)
CALCITONIN. (OSTEOBLAST) BONE
MINERALISASI
MACROPHAGE COLONY-STIMULATING
FACTOR-1,

LARGE, MOTILE, MULTINUCLEATED ,

ACIDOPHILIC CYTOPLASM.

DERIVED FROM

Multinucleate cell, secretes acid

and enzym to dissolve bone matrix

intramembranous
ossification
Osteoclasts (Oc) in

FUSION OF MANY BLOOD-DRIVED

MONOCYTES,

PRECUSOR ORIGINATES IN BONE

MARROW, OSTEOCLAST
PRECUSORS FUSE, MULTINUCEATED

PERIOSTEUM-ENDOSTEUM

DENSE, IRREGULAR, COLLAGENOUS

CONNECTIVE TISSUE,

OUTER FIBROUS LAYER,

(VASCULAR AND NERVE) SUPPLY
O2 & NUTRISIEN

INNER CELLULAR LAYER

(OSTEOPROGENITOR &
OSTEOBLASTS). OSTEOGENESIS,
REMODELING, RECOVERY FRACTURE

SYSTEM OF LAMELLAE

CIRCUMFERENTIAL
EXTERNAL-INTERNAL,

CONCENTRIC (OSTEON
UNIT),

INTERSTITIAL LEMELLAE.

UNIT OSTEON, HAVERS SYSTEM

LAMELLA CONCENTRIC
CEMENT
HAVERS CANAL
OSTOCYTES, LACUNA,
CANALICULI

SYSTEM OF VASCULAR-CANAL NUTRIEN & GASS TRANPORTATION

SYSTEM OF VASCULAR-CANAL

PERIOSTEAL BLOOD VESSEL

PERFORATING (VOLKMAN ,S
CANAL)

HAVERSIAN CANAL

CONTINUOUS INTO MEDULLARY

CAVITY

CANALICULI, LACUNA SPACE

(EXTRACELLULAR FLUID)

EXTRACELLULAR FLUID (PERIOSTEOCYTIC SPACE, CANALICULI),

EXTENSIVE NETWORK OF CANALICULI AND OF PERIOSTEL SPACE

VOLUME (1,3L), AND AREA OF WALLS EXCHANGES (5000 m2) ,

20 g CALCIUM CAN RESOBED

ACCESS TO BLOODS TREAM ENSURES THE MAINTENANCE OF

ADEQUATE BLOOD CALCIUM LEVELS.

BONE RESORPTION

BONE RESORPTION

BONE RESORPTION
OBJECTIVE

IMPORTANT OSTEOCLAST FUNCTION :

GROWTH AND DEVELOPMENT OF BONE

OSTEOGENESIS

REPAIR OF DAMAGE/FRACTURE

PHYSIOLOGY OF THE SCELETON.

HOMEOSTASIS MAINTENANCE Ca BLOOD LEVEL

REMODELING RENEWING BONE TISSUE

PHATOPHYSIOLOGY OF SEVERAL SCELETAL DISEASE

BONE RESORPTION RATE

INCREASED (OSTEOPOROSIS, METATASTIC BONE DISEASE

AND PAGETS DISEASE OF BONE)

DECREASE (VARIUOS SYNDROME OF OSTEOPETROSIS)

CHANISM OF OSTEOCLAST TO BONE RESORPTION

LOW Ph ENVIRONMENT
INORGANIC MATRIX IS
DISOLVED, (Ca)
OSTEOCLAST CYTOPLASM ,
BE DELIVERED TO NERLY
CALILLARIES.

SYNTHESE LYSOSOMAL
ENZYM, SECRESE TO APICAL
RUFFLED BORDER
MEMBRANE

ACIDOPILIC MILIEU

FORMATION OF CARBONIC ACID , ENZYME CARBONIC ANHYDRASE

CATALYSES: CO2 + H2O H2CO3, H+ & HCO3

PROTON PUMPS IN (RUFFED BORDER) ACTIVELY TRANSPORT H+

IONS SUBOSTEOCLASTIC COMPARTEMENT LOW pH OF
MICROENVIRONMENT

REGULATION OF BONE
RESORPTION
(BONE LOSS)
REGULATE THE

NUMBER OF OSTEOCLAST

VIA PRECUSSOR OSTEOCLAST, STIMULATE/INHIBITE

PROLIFERATION AND DIFFERENTIATION
(OSTEOPROGENITOR, OSTEOBLAST, MACROPHAGE, OTHERS)

VIA OSTEOBLAST , INHIBITE TO PRODUCTING FACTOR

THAT ESSENTALE FOR OSTEOCLAST DIFFERENSIATION
(CALSITONIN AND AMINOBIPHAPHONATE),

VIA DIRECT TO OSTEOCLAST, INDUCE APOPTOSIS CELLS

((BISPHOSPHONATE, CLODRONATE)

VIA THE RANK/RNKL/OSTEOPROGETERIN PATHWAY

1. LOCAL FACTORS (PRODUCED IN THE BONE MICROENVIRONMENT)

RANKL (+) (RECEPTOR ACTIVATOR OF NUCLEAR FAKTOR KAPPA B
LIGAND/NF-KB)

PRODUCED BY BONE CELLS (OSTEOBLASTIC LINEARGE CELL &

ACTIVATED T LYMPHOCYTE

RECEPTOR : ON OSTEOCLASTIC PRECUSOR , MACROPHAGE, STROMA

CELL, OSTEOBLAST

FOR OSTEOCLAST FORMATION/DIFFERENTIATION INTO

MULTINUCLEATED OSTC, FUSSION, ACTIVATION & SURVIVAL
INCREASE NUMBER & ACTIVATING OF OSTEOCLAST,

EFFECT OF RNAK CONTRACTED, BY COUNTERACTED BY OPG (ACTS

SOLUBLE NETRALIZING RECEPTOR)

RANKL & OPG ARE REGULATED BY VARIANS HORMON

(GLUCOCORTICOID, PTH, CALCITONIS, VIT D GROWTH HORMON,
TESTOSTERO, ESTROGEN

ABNORMALITIES OF RANK/OPG SYATEM IMPLICATED IN THE

PATOGENIS OF POSTMENOPAUSE OSTEOPOROSIS, RHEUMATID
ARTRITIS, PAGET,S DIS. PERIODONTAL DIS, ETC

 OPG (OSTEOPROGERIN) (-)

= OSTEOCLAST GENESIS INHIBITORY

FACTOR (OCIF), A MEMBER OF THE TUMOR NECROSIS FARTOR RECEPTOR
(TNFR) FAMILY,

PRODUCED BY OSTEOBLAST

RECEPTOR : ON OSTEOCLASTIC PRECUSOR, MACROPHAGE, STROMA

CELL, OSTEOBLAST

OPG RECEPTOR FOR RANKL PREVENTING BINDING TO RANK,

INHIBITOR OF RANKL, BLOCKS THE EFFEK OF RANKL INHIBITS
OSTEOCLAST DIFFERENTIATION

RANKL, CELLULAR RECEPTOR RANK, & DECOY RESEPTOR OPG,

CONSTITUTE NOVEL CYTOKINE SYSTEM.

SYSTEMIC FACTORS, HORMONAL EFFECTS.

REGULATES OSTEOCLASTIC ACTIVITY MAINTAINING A
CONSTAN SUPPLY CALCIUM ION.

1.

PTH; PARENCHYMAL CELLS

(PARATHYROID GLAND)
SENSITIVE TO BLOOD CALCIUM
LEVEL FALL BELOW NORMAL,
INCREASE Ca
RECEPTOR : VIA OSTEOBLAST TO
OSTEOCLAST (LACK PTH RECEPTOR)

PTH ACTIVATES RECEPTOR ON OSTEBLAST,

SUPPRESSING MATRIX FORMATION AND

INITIATING MANUFACTURE AND SECRETION OF OPGL & OSTEOCLASTSTIMULATING FACTOR

INDUCE OSTECLAST FORMATION AND STIMULATE QUIESCENT
OSTEOCLAST (BECOM ACTIVE), RELEASE OF CALCIUM ION.
PTH SLIGHT INCREASED EXPRESSION OF IL-6 mRNA IN PRIMARY
OSTEOBLAST-LIKE CELLS INDUCES BONE RESOPTION

CALCITONIN (CT):

2.

3.

THYROID GLD, PARAFOLLICULAR CELLS (C cells)

CALCIUM ION LEVEL IN PLASMA ELEVATED SECRETE CALCITONIN,

RECEPTOR ON OSTEOBLAST

IMPORTAN ROLES IN Ca HOMEOSTASIS DECREASE Ca

ACTIVATES RECEPTOR ON OSTEOCLASTS, INHIBITE RESORBING

BONE.

STIMULATE OSTEOBLASTS TO INCREASE OSTEOID SYNTHESIS

AND CALCIUM DEPOSITION IS INCREASE.

GROWTH HORMON SOMATOTROPIN (ANT. LOBE OF

PITUITARY GLAND),
BONE DEVELOPMENT VIA SOMATOMEDINS (insulin-like growth
factors), ESPECIALLY STIMULATING GROWTH OF THE
EPIPHYSEAL PLATE.
CHILDREN DEFICIENT THIS HORMONE DWARFISM,
EXCESS SOMATOTROPIN IN THEIR GROWING YEARS
PIPTUTARY GIGANTISM.

REGGULATION OF DIFFERENTIATION OSTEOCLAST

OSTEOBLASTS , SECRETE 3 SIGNALING MOLECULES

REGULATE THE DIFFERENTIATION OF OSTEOCLASTS.
1. SECRETE OSTEOCLAST-STIMULATING FACTOR ACTIVATE
OSTEOCLASTS TO RESORB BONE
2. SECRETE ENZYMES REMOVING OSTEOID
OSTEOCLASTS CAN MAKE CONTACT WITH MINERALIZED BONE
SURFACE
3. OPG, (IS PRODUCED NOT ONLY BY OSTEOBLAST), BY
CELLS OTHER TISSUE (CARDIOVASCULAR SYSTEM, LUNG,
KIDNEY, ISTESTINES, HEMAPOETIC AND IMMUNE CELLS).
. IN BONE, OPG ALSO SUPRESSES THE OSTEOCLASTS
BONE RESOPTIVE CAVITIES. (NOT ONLY INHIBITS THE
DIFFERENTIATION OF PRECUSOR CELLS INTO OSTEOCLAST)

REMODELING OF BONE

REMODELLING OF BONE

Osteoclast

Howships lacuna

DEFINITION:

PHYSIOLOGICAL , CONTINOUS
RENEWING BONE DURING LIFELONG

MATUR BONE TISSUE IS REMOVED (BONE

RESORPTION) AND NEW BONE TISSUE IS
FORMATED (OSSIFICATION),

CONTINOUS TURNOVER OF BONE TO

MAINTENANCE NORMAL BONE MASS.

REMODELING FUNGTIONAL, ADAPTATION WITHIN THE

SCELETON, ACTIVE AND DYNAMIC PROCESS CORRECT BALANCE
BETWEEN BONE FORMATION /DEPOSITION AND BONE
RESORPTION,

IN YOUNG PERSON, BONE DEVELOPMENT EXCEES

RESORPTION ,

IN ADULTHOOD, EPIPHYSEAL PLATES CLOSE AND BONE GROWTH

HAS BEEN ATTAINED,
NEW BONE DEVELOPMENT IS BALANCED WITH BONE
RESORPTION.
CONTINUING REMODELING TO MEET STRESSES PLACED ON

OBJECTIVE

PHYSIOLOGICAL PROCESS, NECESSARY FOR:

1.

TO HEMOSTASIS CALCIUM (CALCIUM METABOLIC)

2.

TO REORGANITATION OR RENOVATION OF OLD STRUCTURE

OF BONE (RENEWING BONE TISSUE)

3.

TO MAINTENANCE NORMAL BONE MASS,(HELATHY BONE),

TO ENSURE MAINTENNCE OF NORMAL BONE MASS AS
PERSONE AGES FISRT YEARS OF LIFE , 100% OF THE
SCELETON IS REPLACE, IN ADULT 10%/YEAR

4.

TO CONTROLE THE RESHAPING OR REPLACEMENT OF

BONE FOLLOWING:

INJURY (FRACTURE) OR MICRODAMAGE WHICH ACCOR

DURING NORMAL ACTIVITY

MECANICAL STRESSING OF PHYSISC OCCUR IN BONE,

STRUCTUR SUPPORT

PROCESS OF REMODELING

BONE REMODELING, 3 PHASES

1.

RESORPTION MATRIX :
OSTEOCLAST OSTEOCLAST BREAK
DOWN BONE AND RELEASE THE
MINERAL (RESORPTION OF BONE)

2.

REVERSAL : MONONUCLEAR CELLS

APPEARS ON BONE SURFACE

3.

FORMATION NEW BONE :

OSTEOBLASTS, LAY DOWN NEW BONE
REPLACED RESORBED BONE
COMPLITELY

ACTIVATION OF OSTEOCYTS, OSTEOBLAST, OSTEOCLASTS ARE

REGULATED BY PRAHORMON AND HORMON (PTH, CALCITONIN,
TESTOSTERON, ESTROGEN, VIT D. )

HISTOGENESIS OF BONE
1. INTRAMEMBRANOUS BONE
FORMATION/OSSIFICATION
2. ENDOCHONDRAL ONE
FORMATION/OSSIFICATION

HISTOGENESIS OF BONE

BONE FORMATION (OSSIFICATION)

DURING EMBRYONIC DEVELOPMENT & REPAIR OF

FRACTURE BONE

FIRS BORNE FORMED, PRIMARY BONE (IN GROW), AND LATER

RESORBED AND REPLACED BY SCONDARY BONE. (MATURE
BONE)

SECONDARY BONE CONTINUES TO BE RESORBED THROUGHOUT

LIFE, ALTHOUGH AT SLOWER RATE. (REMODELING)

PROCESS INTRAMEMBRANOUS
OSSIFICATION (PLATE BONE)
WITHIN MESSECHYMAL TISSUE
(PRIMARY OSSIFICATION
CENTER)
1.

MESSENCHYMAL CELLS FORM AGRGREAGATION

DIFFERENTITE INTO OSTEOBLASTS BONE MATRIX
(OSTEOID)

2.

OSTEOBLASTS POPULATION ON SURFACE

BONE GROW IN LINEAR EXTENSIONS (SPICULES).
A NETWORK OF TRABECULAE

3.

CALCIFICATION QUICKLY FOLLOWS OSTEOID

FORMATION, OSTEOBLAST TRAPPED IN BONE
MATRICES, OSTEOCYTES, IN LACUNA AND A
SYSTEM OF CANALICULI.

4.

MULTIPLE OSSIFICATION CENTERS , ENLARGE

FUSION OF SPICULES IN THE TRABECULAR NETWORK
(CHARATERISTC OF SPONGY BONE).

5.

REMODELING, PRODUCES SPONGY BONE,

MARROW CAVITIES AND COMPACT BONE
CHARASTERITIC OF MATURE BONE.,

ADDITION OF TRABECULAE
INCREASE THE SIZE

LARGE BONE, (OCCIPATLE), HAVE

SEVERAL OSSIFICATION CENTER,
FUSE TO FORM SINGLE BONE.

REMAIN REGIONS OF MESSENCHYMAL

TISSUE UNCALCIFIED
DIFFERENTIATED INTO THE
PERIOSTEUM AND ENDOSTEUM OF
DEVELOPING BONE.

ENDOCHONDRAL BONE FORMATION

N LONG AND SHORT BONES

REQUIRES THE PRESENCE OF CARTILAGE TEMPLATE (HYALINE)

SEVERAL PHASE PROCESS

1.

FORMATION & GROWTH OF HYALIN CARTILAGE MODEL,

2.

PRIMARY OSSIFICATION CENTER

3.

SECONDARY OSSIFICATION CENTER

4.

BONE GROWTH IN LENGTH AND GROWTH IN WIDTH

5.

REMODELING

PROCESS OF ENDOCHONDRAL FORMATION/OSSIFICATION

A. HYALINE CARTILAGE MODEL GROWS (INTERSTITIEL &
APOSITIONAL)
B. CARTILAGE AT MIDRIFF (DIAPHYSIS) IS INVADED BY
VASCULAR
C. IN THE CENTER OF DIAPHYSIES, CHONDROCYTES
HYPERTHROPY, MATRIX BEGIN TO CALCIFIED
DEFICIT NUTRIENTS DIE, LEAVING CAVITIES,
WITHIN THE CALCIFIED CARTILAGE MATR
D. PERICHONDRIUM TRANSFORM INTO PERIOSTEUM
(OSTEOGENIC LAYER).
OSTEOCLAST INVADE, ETCH BONE TO PERMiT
PERIOSTEAL BUD TO FORM, CAPILLARIES,
OSTEOPROGENITOR CELLS PERIOSTEUM MIGRATE
INTO , OSTEOBLASTS REPLACE PRODUCES SPONGY
BONE. BECOMES PRIMARY OSSIFICATION CENTER
IN DIAPHYSES.
A SUBPERIOSTEAL THIN BONY COLLAR ARROUND THE
SHAFT OF CARTILAGE MODEL. ,
E. EPIPHYSES BECOME FILLED WITH SPONGY BONE. A
THIN CAP OF CARTILAGE REMAINS (ARTICULAR
CARTILAGE), METHAPHYSEAL PLATE SPARATES THE
EPIPHYSES FROM DIAPHYSIS.
F.

CENTER OF DIAPHYSES NOW BEGIN TO CALCIFIED,

CAPILLARES AND OSTEOBLAST MIGRATE TO THESE AREA
CREATING SECUNDARY OSSIFICATION CENTER.

Endochondral bone formation (14).

The upper half; cartilage (C) containing

chondrocytes mature, hypertrophy, and
calcify at the interface (matrix);

The lower half : calcified cartilage/bone

complex (arrows) is being resorbed and
bone (b) is being formed. P, periosteum.

Endochondral bone formation (270).

The trabeculae of calcified cartilage (CC)
are covered by a thin layer of bone (darker
red) with osteocytes embedded in it
(arrows) and with osteoblasts (Ob) lying
next to the bone

ONE GROWTH IN LENGTH

THE CONTINUED LENGTHENING OF BON

DEPENDS ON THE EPIPHYSEAL PLATE.

EPIPHYSEOUS FILLED WITH SPONGY BONE,

THIN HYALIN CARTILAGE REMAIN
ARTICULAR SURFACE (ARTICULAR
CARTILAGE).

EPIPHYSEAL PLATE : CHONDROCYTES

PROLIFERATE, THE PROCESS OF
ENDOCHONDRAL BONE FORMATION.
(PROLIFERATION AT EPIPHYSEAL
ASPECT, REPLACEMENT BY BONE AT
THE DIAPHYSEAL SIDE (TAKES PLACE).

THE EPIPHYSEAL PLATE SPARATE THE

BONE OF THE EPIPHYSES FROM DIAPHYSIS.
GROWTH IN THE LENGTH

EPIPHYSEAL PLATE IS DIVIDED INTO 5 ZONE

1). ZONE OF RESERVE CARTILAGO:
CHONDRCYTES RANDOMLY DISTRIBUTED,
MITOCALLY ACTIVE.
2). ZONE OF PROLIFERATION: CHONDROCYTES
RAPIDLY PROLIFERATING, FORM ROWS OF
ISOGENOUS CELLS THAT PARALLEL DIRECTION
OF BONE GROWTH.
3). ZONE OF MATURATION & HYPERTROPHY :
CHONDROCYTES HYPERTROPHY,
ACCUMULATE GLYCOGEN , LACUNA >,
MATRIX BETWEEN LACUNAE NARROW.
4). ZONA OF CALCIFICATION : LACUNAE
BECOME CONFLUENT, HYPERTROPHIED
CHONDROCYTES DIE, MATRIX CALCIFIED.
5). ZONE OF OSSIFICATION:
OSTOEPROGENITOR CELLS INVADE THE AREA,
DIFFERENTIATE INTO OSTEOBLASTS,
MATRIX CALCIFIED (ON THE SURFACE OF
CALCIFIELD CARTILAGE). FOLLOW
RESORPT THE CALCIFIED CARTILAGE/CALCIFIED
BONE COMPLEX.

BONE GROWTH IN WIDTH

BY APPOSITIONAL GROWTH REPLACED BY BONE (BONE

LENGTHENING BY PROLIFERATION AND INTERSTITIAL
GROWTH OF CARTILAGO,.

OSTEOPROGENITOR CELLS (PERIOSTEUM) INTO

OSTEOBLAST SUBPERIOSTEAL BONE SURFACE.

CINTINUOUSLY THROUGHT THE TOTAL PERIODE OF BONE

GROWTH AND DEVELOPMENT,

DURING BONE GROWTH AND DEVELOPMENT, RESORPTION

IS AS IMPORTANS AS DEPOSISITION. FORMATION OF BONE ON
THE OUTSIDE, MUST BE ACCOMPANIED BY OSTEOCLASTIC
ACTIVITY INTERNALLY THE MARROW SPACE BE ENLARGED.

REPAIR OF BONE FRACTURE

REPAIR OF BONE FRACTURE

FRACTURE DAMAGE OF TISSUE

BREAK OF VASCULLAR
BLEEDING CLOTING BLOOD

BONE CELLS WILL DIE (NO

NUTRITION) AND AREA WILL BECOME
IRRITATED.

4 STEPS TO REPAIR OF BONE FRACTURE

4 STEPS TO REPAIR OF BONE

FRACTURE
1.

HEMATOMA -BLOOD VESSEL,

BONE CELL WITH NO NUTRITION
WILL DIE AND AREA WILL BECOME
IRRITATED..

2. FIBROCARTILAGINOUS CALLUS
(SOFT CALLUS) FORMATION.
INVADE FIBROBLAST AND
HYPERVASCULARITATION
FORM GRANULATION
DEVELOPING BLOOD VESSELS,
AND FIBROCARTILAGE FORMS
3.

BONE CALLUS (HARD CALLUS)

FORMATION, ABOUT 1 WEEK
NEW BONE BEGIN TO REPAIR (A
BONY CALLUS) 3 MONTHS BONY
CALLUS REPLACE THE
FIBROCARTILAGE

4.

BONE REMODELING,

INITIAL EVENTS INVOLVED IN FRACTURE HEALING

OF LONG BONE.
PERIOSTEUM IS TORN OPPOSITE THE SPOT OF
IMPACTAND, IN MANY INSTANCE, IS INTACT ON
OTHER SIDE
AN ACCUMULATION OF HEMATOMA BENEATH
THE PERIOSTEUM AND BETWEEN THE FRACTURE
END
NECROTIC MARROW AND DEAD BONE CLOSE
TO THE FRACTURE LNE

EARLY REPAIR. THERE IS ORGANIZATION OF

HEMATOMA, EARLY PRIMARY NEW BONE
FORMATION IN SUBPERIOSTEAL REGION, AND
CARTILAGE FORMATION IN OTHER AREAS.

AT LATER STAGE IN THEREPAIR, EARLY IMMATURE

FIBER BONE IS BRIDGING THE FRACTURE GAP
PERSISTENT CARTILAGE IS SEEN AT POINTS MOST
DISTANT FROM INGROWING CAPILLARY BUSD
IN MANY INSTANCES, THESE ARE SUROUNDED BY
YOUNG NEW BONE.

CLINICAL CORRELATIONS

IF FRAGMENTS OF BONE ARE LOST, OR DAMAGED SO SEVERELY

THAT THEY HAVE TO BE REMOVE, "bony union" IS NOT POSIBLE

PROCESS BONE REPAIR CANNOT ACCUR (BONY CALLUS DOES

NOT FORM).

IN THIS CASES, A BORNE GRAFT IS REQUIRED

AUTOGRAFTS MOST SUCCESFUL BECOUSE RECIPIENT IS DONOR.

HOMOGRAFTS DONOR FROM DOFFERENT INDIVIDUAL, MAY BE

REJECTED (IMMUNOLOGICAL RESPONS)

HETEROGRAFTS, GRAFTS FROM DIFFERENT SPECIES, LEAST

SUCCESSFUL, ALTHOUGH CALFT BONE LOSES SOME OF ITS
ANTIGENICITY WORTHY BONE GRAFT WHEN NECESSARY.

BONE DESEASES

BONE DISEASES
Due to inadequate osteoid
e.g.,

Vitamin C

Scurvy

Due to inadequate mineralization

e.g., Ca++, PO4, Vitamin D
Due to excessive resorption
e.g., osteoporosis
Endocrinopathies

rickets
osteomalacia

CLINICAL CORRELATIONS
ACROMEGALY.

ADULT WHO PRODUCE AN EXCESS OF SOMATOTROPIN,

ABNORMAL INCREASE IN BONE DEPOSITION (WITHOUT
NORMAL BONE RESORPTION).

THICKENING OF THE BONES, ESPECIALLY OF FACE,

CLOSURE OF THE EPIPHYSEAL PLATE IS NORMALLY RATHER

STABLE AND CONSTANT ( >> SEXUAL MATURATION).

PRECOCIOUS SEXUAL MATURATION STUNT

SKELETAL DEVELOPMENT EPIPHYSEAL PLATE CLOSE
TOO EARLY.

SEXUAL MATURATION IS RETARDED, SKELETAL

GROWTH CONTINUES BEYOND NORMAL LIMITS
EPIPHYSEAL PLATE NOT CLOSE.

CLINICAL CORRELATIONS
OSTEOPOROSIS

DECREASING OF BONE MASS

CHRONICALLY IMMOBILIZED, >> WOMEN OLDER 40,

ESPECIALLY POSTMENOPAUSAL WOMEN, MORE SERIOUS AFTER

MENOPAUSE, (ESTROGEN SECRETION DROPS). OFTEN

BINDING ESTROGEN TO SPECIFIC RECEPTOR ON

OSTEOBLASTS ACTIVES TO MANUFACTURE AND
SECRETE BONE MATRIX.

DIMINISHED ESTROGEN, OSTEOCLASTIC ACTIVITY IS

GREATER THAN BON DEPOSITION, REDUCTING BONE MASS

ESTROGEN REPLACEMENT (+). BUT INCREASE THE RISK .

EARLY DIAGNOSTIC

NUTRITIONAL EFFECTS (IN NORMAL GROWTH)

NORMAL BONE GROWTH IS SENSITIVE AND DEPENDENT ON

SEVERAL FACTORS.
PROTEIN, MINERAL, AND VITAMINS, THE AMNOACIDS ESSENTIAL
FOR COLLAGEN SYNTHESSIS (BY OSTEOBLASTS).
CALCIUM AND PHOSPHORUS CALCIFIED MATRIX
VIT. D, CALCIUM ABSORBTION FROM INTESTINE (RICKETSIA IN
CHILDREN)
VIT. A & C, NECESSARY FOR PROPER SKELETAL
DEVELOPMENT(SCURVY)

OSTEOMALACIA= ADULT RICKETS

PROLONGED DEFICIENCY VITAMIN D.

NEWLY FORMED BONE IN PROCESS OF REMODELING DOES NOT
CALCIFIED.
MAY BECOME SEVERE DURING PREGNANCY BECAUSE THE FETUS
REQUIRES CALCIUM, WHICH MUST BE SUPPLIED BY THE MOTHER.

SCURVY.

DEFICIENCY OF VITAMIN C.
DEFICIENT COLLAGEN PRODUCTION, REDUCTION IN FORMATION
OF BONE MATRIX AND BONE DEVELOPMENT.
HEALING IS DELAYED

RICKETS
DISEASE IN INFANTS AND CHILDREN, DEFICIENT IN VIT D. THE
INTESTINEAL MUCOSA CANNOT ABSORB CALCIUM
DISTURBANCES IN OSSIFICATION OF THE EPIPHYSEAL TO POORLY
CALCIFIED BONE MATRIX.
DEFORMED BONE PARTICULARLY IN THE LEGS, BECAUSE THE BONE
CANNOT BEAR THEIR WEIGHT.

JOINT

BONE ARTICULATE ,

1) SYNARTHROSES. ONLY MINIMUM MOVEMENT,

2, DIARTHROSES FREE TO ARRTICULAE , WIDE RANGE

OF MOTION

SYNARTHROSIS JOINT: 3 TYPES, (TISSUE MAKING UP

THE UNION)

1) SYNOSTOSIS, JOINT UNITING TISSUE IS BONE

(e.g., SKULL BONE IN ADULT),

2) SYNCHONDROSIS, JOINT UNITING TISSUE IS

HYLANIN CARTILAGE (e.g., JOINT OF FIRST RIB
STERNUM),

3) SYNDESMOSIS, BONES ARE JOINED BY DENCE

CONNECTIVE TISSUE (e.g., PUBIC SYMPHYSIS).
LONG BONE, DIARTHROSIS (MOST JOINTS OF
EXTREMITIES).

ARTICULAR SURFACE, HYALIN CARTILAGE

(ARTICULAR GARTILAGE).

LIGAMNETS MAINTEN THE CONTACT BETWEEN BONES.

JOINT CAPSULE : 1). OUTHER FIBROUS LAYER

CONNECTIVE TISSUE CONTINOUS WITH PERIOSTEUM, 2)
INNER CELLULAR SYNOVIAL LAYER,(SYNOVIAL
MEMBRANE), COVER ALL NONARTICULAR SURFACE.

TYPE CELLS

IN SYNOVIAL LAYER :

1). TYPE A CELLS ARE MACROPHAGES PHAGOCYTIC CELLS

RESPONSIBLE FOR REMOVING DEBRIS FROM JOINT SPACE.

2). TYPE B CELLS RESEMBLE FIBROBLAST, TO SECRETE THE

SYNOVIAL FLUID.

SYNOVIAL FLUID

HIGH CONCENTRATION OF HYALURONIC ACID AND GLYCOPROTEIN

LUBRICIN COMBINE WITH FILTRATE OF PLASMA.

TO SUPPLYING NUTRIENS AND OXYGEN TO CHONDROCYTES OF

ARTICULAR CARTILAGE, TO LUBRICANT FOR JOINT (HIGH CONTEN
HYALURONIC ACID AND LUBRICIN).

MACROPHAGE IN SYNOVIAL FLUID ACT TO PHAGOCYTOSES DEBRIS

IN JOINT SPACE.

DOKTER ADALAH PILIHANKU

PROSES ADALAH IKHTIAR DAN
PENGKODISIANKU
RIDHO ALLAH DOAKU

SUKSES UNTUK MU,

AMIIIIN.