BONE DEVELOPMENTBONE DEVELOPMENT

Evolution of bone

Experiments with calcified cartilage

Bone povided rigid support

New features introduced with advent of bone

1. Canalicular system

means of diffusive communication

boundaries: open to tissue spaces

enabled metabolism in osseus tissue

2. Internal vascularity

Canalicular system effective only up to 0.2mm from tissue fluid

Vascular supply in matrix = solution

Vessels in Haversian canals and Volkmann’s canals

Interaction of canalicular system and vascularity bone can live indefinitely

3. Appositional growth – new type

Interstitial growth not possible

Thickness same plan as cartilage

Elongation new type of appositional growth

Epiphyseal plate (disk) – grows from outer edge, inner edge replaced by bone

4. Reconstruction

Local destruction with bone reformed

After birth new matrix deposited in layers

During reconstructions Haversian systems formed (some sites)

Parallel lamellae (periosteal and endosteal) laid down last

HISTOGENESIS OF BONE / OSTEOGENESISHISTOGENESIS OF BONE / OSTEOGENESIS

Two types of bone formationTwo types of bone formation

Intramembranous bone formationIntramembranous bone formation

Intracartilaginous bone formation or Intracartilaginous bone formation or (Endochondral bone formation)(Endochondral bone formation)

Types refer to “environment” where development Types refer to “environment” where development occursoccurs

Types of formation are generally similarTypes of formation are generally similar

Generalities:

Specialized cells of bone development

Osteoblast

From mesenchymal cells

medium sized cells

Associate in continuous layer along edge of forming bone

Cuboidal shape deeply basophilic with special granules in cytoplasm for ground substance

“Paler” cells depleted

Collagenous fibers of matrix are osteocollagenous fibers

Cytoplasm contains alkaline phosphatase (deposition of matrix)

Osteoblasts – delicate processes – along fibers and surface of forming bone

Process forshadow canaliculi

Become trapped in matrix

Become OsteocytesOsteocytes

Bone forming role ceases except lacunar capsule

OSTEOCLASTS

Giant cells of bone developmentGiant cells of bone development

Large Large mulitnucleatedmulitnucleated cells up to 100 cells up to 100 μμ

several to dozens of nucleiseveral to dozens of nuclei

Pale to acidophilic, foamy cytoplasmPale to acidophilic, foamy cytoplasm

Found where bone matrix is being Found where bone matrix is being resorbedresorbed

In regions of calcified cartilage they In regions of calcified cartilage they are called are called chondroclasts

Occupy shallow pits (Occupy shallow pits (Howship’s lacunaeHowship’s lacunae))

Fringe by matrix (striate border?)= ruffled borderFringe by matrix (striate border?)= ruffled border

Role of Osteoclast in matrix absorption

Phosphatase enzymes released by cell

Hydroxyapatite seen in osteoclasts

Osteoclasts phagocytic

Osteoclasts release enzymes to dissolve bone matrix

Matrix remnants in cytoplasm

Parathyroid hormone promotes resorption

Calcitonin from thyroid parafollicular cells inhibits

Parathormone and calcitonin = counterbalance

Osteoclast origin

Mononuclear hemopoietic progenitor cells

CFU-GM neutrophilic granulocytes and monocytes

CFU-M monocytes

(CFU = Colony Forming Unit)

CFU-GM and CFU-M related to macrophages

Product of cell fusions rather than nuclear divisions

Tissue ParticipantsTissue Participants

Primitive MarrowPrimitive Marrow

Vascular mesenchyme provides osteoblasts and blood vessels

Formation of spongy bone

Perichondrium of cartilage bone vascular bud into bone model

Perichondrium becomes periosteum

Cartilage breaks down as bud Cartilage breaks down as bud advancesadvances

Tissue differentiation Tissue differentiation primitive primitive marrow and osteoblastsmarrow and osteoblasts

PeriosteumPeriosteum

Inner layer of primitive periosteum

Acquires osteogenic ability

Sheet of osteoblasts from on inner surface

Deposition of bone matrix

Early bone is “spongy”

Later bone deposited is compact

Reabsorption along surface of periosteum-bone contact

Area of resportion

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EndosteumEndosteum

Peripheral layer of marrow tissue is osteogenic

endosteal lamellae

Surface of endosteum is also osteogenic

Site of extensive resorption of bone

CartilageCartilage

Temporary fetal skeleton

Develops rapidly can keep up with rapid fetal growth (bone cannot)

Gives rise to unique epiphyseal plates

Growth in length of bone

Cartilage proliferates

Cartilage destroyed

Bone deposited on remnants of bone

OSTEOGENESISOSTEOGENESIS

Spicular boneSpicular bone – arise at multiple sites

Osteoblasts start matrix formation

1st matrix is osteocollagenous fibers and amorphous ground substance

= provisional matrix (soft) is osteoid tissue

Next step – deposition of calcium salts

With calcium salts = definitive matrix

Finally osteoblasts cover the spicule

Added matrix under osteoblast increases spicule thickness

Laggard osteoblasts become trapped in matrix

Replaced from mesenchyme

Deposition of matrix around osteoblast creates lacunae around cell body and canaliculi around cell processes

Tip of spicule: osteoblasts and osteocollageous fibers produce brush-like arrangement

Spongy boneSpongy bone – union of spicules produces spongy bone

Continued deposition (matrix) makes trabeculae thicker and entire mass more compact

Early bone not formed in layers, fibers in random interlacing directions

Lamellar boneLamellar bone

After birth – fetal bone replaced

Fetal bone irregularly interwoven, unlayered

Repeated erosions and replacement not enough

Definitive (adult) bone is lamellated (= lamellar bone)

Includes Spongy and Compact bone

INTRAMEMBRANOUS BONE FORMATIONINTRAMEMBRANOUS BONE FORMATION

Product = membrane bones

Means: the bone formed in mesenchyme

Mesenchyme = cellular and fibrillary plate (membrane)

Pure membrane bones: flat bones of cranial vault; irregular bones of face

Mixed membrane/Carilage bones: occipital, temporal, sphenoid

Early development (membrane bones)

Sheet of primitive C.T. (old mesenchyme)

One or more start points (ossification centers)

8th week of fetal life

centers are richly vascular; actively proliferative

Spicules begin in center

elongate

radiate out from center

wheel-like pattern

branching/anastomosis of spicules

thickness subordinate to spreading growth

Birth: most meet along margins

Surrounded by periosteum

Inner surface osteoblasts thicken bony mass

Thickening trabeculae reduce interspaces

Space filled with marrow and vessels

Later development

At birth – cranial bones simple bony plates (entirely spongy)

Periosteum now lays down parallel lamellae

Table forming (compact bone)

Thinning of trabeculae opens interior (diploe)

Enlarging brain – calvarium remodeled to fit

Calvarium gains more gentle curvature

appositional growth largely outer surface

resorpiton largely inner surface

Haversian systems form in compact bone

INTRACARILAGINOUS BONE FORMATIONINTRACARILAGINOUS BONE FORMATION

ENDOCHONDRAL BONE FORMATIONENDOCHONDRAL BONE FORMATION

Most bones of the skeleton

Preceded by cartilaginous model

Eroded and replaced by bone

Ossification occurs in the eroding mass

Long bones simplest picture of endochondral formation

Primary center in shaft (diaphysis)

Secondary center in each end (epiphysis)

Primary centers – second fetal month

latest forming primary centers (wrist, ankle) in childhood

Secondary centers – a few present before birth

Majority appear in childhood or adolescence

The Beginnings: Early History of Cartilaginous model

Condensed mass of mesenchyme

Forms precartilage

Later becomes hyaline cartilage

Periphery: fibrous sheath, the perichondrium

Primary center1st indications changes in cartilage cells

internally, midway shaft (diaphyseal center)

cells enlarge, intervening matrix thins

Enlarged cells secrete alkaline phosphatase

Calcium salts deposited in matrix

= calcified cartilage

Cells soon die

Walled off from nutrients

Without these cells, matrix becomes unstable

Matrix begins to dissolve

Irregular cavities formed

Periosteal bone collar

Inner, cellular layer perichondrium now active

Some cells become osteoblasts

Form osteogenic layer

Thin (cylindrical) collar of bone matrix forms around cartilage

Encloses middle 1/3 of cartilage model

Perichondrium is now Periosteum

Bone collar forms in intramembranous manner

= Periosteal bone

= splint – compensates for loss of strength

IRRUPTIVE PERIOSTEAL BUDS

Vascular C.T. from periosteum forms a bud

Pushes through breaks in bone collar

This mass is the irruptive periosteal bud

Encounters altered cartilage of primary center

Paritions between cartilage cells dissolves

Cartilage cells die

Lacunar spaces open up

Tissue of bud proliferates rapidly in center of shaft

Some cells become osteoblasts; invading mass is primary marrow

EARLY ENDOCHONDRAL BONE

Osteoblasts line up on remnants of calcified cartilage (scaffolding)

Encrust calcified cartilage with thin layer of bone

Remnants were an irregular meshwork

Thus, early bone is spongy

Osseus mass formed is primary ossification center

GROWTH IN LENGTH

Advance of Ossification from Primary Center

Carilaginous models elongates by interstitial growth

Endochondral ossification spreads toward ends

Events similar to formation of primary ossification center

Series of transverse zones

Each zone changes character as ossification advances on it

Cells forming zones 1, 2, 3 soon comprise 2, 3, 4 and later 3, 4, 5

THE ZONES (FROM ENDS OF CARTILAGE THE ZONES (FROM ENDS OF CARTILAGE TOWARD PRIMARY OSSIFICATION CENTERTOWARD PRIMARY OSSIFICATION CENTER

1.1. Quiescent (Reserve) ZoneQuiescent (Reserve) Zone

Primitive hyaline cartilage

Slight, slow growth

Extensive at first – progressively smaller

2.2. Proliferative ZoneProliferative Zone

Active mitotic zone

Cells divide, daughter cells divide, etc.

Forms rows of cells

Rows parallel with long axis of cartilage

Rows add cells at distal (free) end

Cells in rows are crowded, flattened, separated by very little matrix

More matrix between rows

Arrangement adds length not breath to cartilage mass

3.3. Maturation ZoneMaturation Zone

Mitosis ceases

Cells and lacunae enlarge (cuboidal shape)

Increases length even more

This growth is interstitial

Maturing cells produce more phosphatase and glycogen

4.4. Calcification ZoneCalcification Zone

Deeply basophilic, calcified matrix

Zone is narrow

Cells at peak of life cycle

5.5. Regressive ZoneRegressive ZoneCartilage cells dyingMatrix between cells dissolving (open up

lacunae)Thicker plates of cartilage not eroded

significantlyVascular primary marrow extends into new

spaces

6. Ossification Zone6. Ossification Zone

Osteoblasts migrate to calcified cartilage

Rapid deposition of bone

Adds to spongy bone already present

7. Osseus Zone7. Osseus Zone

Zone of endochondral bone from ossification region to primary center

8. Resorptive Zone8. Resorptive Zone

Advance of ossification toward cartilage offset

Compensatory resorption of bone

Resorption at oldest (proximal) end of bony mass

Keeps mass of spongy bone nearly constant

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SECONDARY CENTERS OF OSSIFICATIONSECONDARY CENTERS OF OSSIFICATION

After birth – in remaining cartilage

At each end of long bones

Sequence of events like those in the shaft

Proliferating cartilage cells form irregular clusters – not rows

Vascular osteogenic tissue

Tunnels form shaft

Osteoblasts from this mass lay down bone on calcified cartilage in epiphysis

Ossification spreads in all directions

Cartilage left on articular surface

Cartilage remains as plate/disk between primary and secondary centers of ossification

Growth is from the proximal surface (shaft side) not the distal surface

Growth in Thickness (Diameter)

Deposition of new periosteal bone

= appositional growth (intramembranous formation)

cannot continue indefinitely

the bone would be too tick-walled and heavy

marrow cavity also must increase in size

bone added to outside (controlled)

smaller amount resorbed inside

Gross Remodeling

Bone a plastic tissue

Adapts external shape and internal architecture

Meets new requirements

Stesses: accidents, disease, use, & disuse

Fetal period also undergoes changes to meet demands

Thick ends thin shaft

Unlike a sculptor working in clay

INTERNAL REOGANIZATION

Gross changes and environment internal reoganization

Alterations are experiments

Alternate waves of construction & destruction

Over-deposits and over-resorptions gradually corrected

After birth – periosteal bone – compact, lamellae

Haversian systems establish

Origins:

earlier systems from longitudinal tunnels (advancing epiphyseal disk)

Earliest systems are “Primitive Haversian Systems”

Later:

cylindrical canals dissolved from compact bone of shaft

Other from longitudinal grooves beneath periosteum

Early & late systems develop the same

Tunnel lined with osteoblasts

At least one blood vessel in space

Successive layers of bone formed from outside inward

Spacious tunnel progressively reduced

Slender canal around vessel remains

VARIATIONS IN OTHER TYPES OF BONES

Short/Irregular bones

Short bones

Center of ossification

Spongy bone spreads – all directions

Periphery – thin layer cartilage remains

Proliferative zone

Internal growth done external shell replaced by bone

Irrelgular bones

May have several ossification centers

Growth spreads from these centers

Vertebrae good example

Body has single center – like short bone

Each vertebral arch has a center

growth spreads out

also spreads into processes

Three secondary centers and disks

Scapula (a flat bone) 2 primary centers and 7 secondary centers