BONE 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 / OSTEOGENESIS
Two types of bone formation
Intramembranous bone formation
Intracartilaginous bone formation or
(Endochondral bone formation)

Types refer to “environment” where development

occurs
Types 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 Osteocytes
Bone forming role ceases except
lacunar capsule
OSTEOCLASTS
Giant cells of bone development
Large mulitnucleated cells up to 100 μ
several to dozens of nuclei
Pale to acidophilic, foamy cytoplasm
Found where bone matrix is being
resorbed
In regions of calcified cartilage they
are called chondroclasts
Occupy shallow pits (Howship’s lacunae)
Fringe 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 Participants
Primitive 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
advances
Tissue differentiation  primitive
marrow and osteoblasts
Periosteum
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
Cartilage growth

Replacement by bone
Area of resportion
Endosteum
Peripheral layer of marrow tissue is osteogenic
endosteal lamellae
Surface of endosteum is also osteogenic
Site of extensive resorption of bone
Cartilage
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
 OSTEOGENESIS
Spicular 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 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 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 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 FORMATION
ENDOCHONDRAL 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 center
1st 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
TOWARD PRIMARY OSSIFICATION CENTER

1. Quiescent (Reserve) Zone

Primitive hyaline cartilage
Slight, slow growth
Extensive at first – progressively smaller
2. Proliferative 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. Maturation 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. Calcification Zone
Deeply basophilic, calcified matrix
Zone is narrow
Cells at peak of life cycle
5. Regressive Zone
Cartilage cells dying
Matrix between cells dissolving (open up
lacunae)
Thicker plates of cartilage not eroded
significantly
Vascular primary marrow extends into new
spaces
6. Ossification Zone
Osteoblasts migrate to calcified cartilage
Rapid deposition of bone
Adds to spongy bone already present

7. Osseus Zone
Zone of endochondral bone from ossification
region to primary center
8. 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
1 4
2 7
6 8
3
5
 SECONDARY 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
 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