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Bones Continues…
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Stages of Intramembranous Ossification
Results in the formation of cranial bones of the skull
(frontal, perietal, occipital, and temporal bones) and the
clavicles.
All bones formed this way are flat bones
An ossification center appears in the fibrous connective
tissue membrane
Bone matrix is secreted within the fibrous membrane
Woven bone and periosteum form
Bone collar of compact bone forms, and red marrow
appears
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Stages of Intramembranous Ossification
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
Figure 6.7.1
Stages of Intramembranous Ossification
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Figure 6.7.2
Stages of Intramembranous Ossification
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Figure 6.7.3
Stages of Intramembranous Ossification
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Figure 6.7.4
Endochondral Ossification
Secondary
ossificaton
center
Deteriorating
cartilage
matrix
Hyaline
cartilage
Primary
ossification
center
Spongy
bone
formation
Epiphyseal
blood vessel
Medullary
cavity
Articular
cartilage
Spongy
bone
Epiphyseal
plate
cartilage
Bone collar
1 Formation of
bone collar
around hyaline
cartilage model.
Blood
vessel of
periosteal
bud
2 Cavitation of
the hyaline cartilage within the
cartilage model.
3 Invasion of
internal cavities
by the periosteal
bud and spongy
bone formation.
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4 Formation of the
medullary cavity as
ossification continues;
appearance of secondary ossification
centers in the epiphyses in preparation
for stage 5.
5 Ossification of the
epiphyses; when
completed, hyaline
cartilage remains only
in the epiphyseal plates
and articular cartilages.
Endochondral Ossification
Results in the formation of all of the rest of the
bones
Begins in the second month of development
Uses hyaline cartilage “bones” as models for bone
construction
Requires breakdown of hyaline cartilage prior to
ossification
Formation begins at the primary ossification center
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Endochondral Ossification
The perichondrium covering the hyaline cartilage
“bone” is infiltrated with blood vessels converting
it to vascularized periosteum.
This change in nutrition causes the underlying
mesenchymal cells to specialize into osteoblasts
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Stages of Endochondral Ossification
Formation of bone collar
Cavitation of the hyaline cartilage
Invasion of internal cavities by the periosteal bud,
and spongy bone formation
Formation of the medullary cavity; appearance of
secondary ossification centers in the epiphyses
Ossification of the epiphyses, with hyaline
cartilage remaining only in the epiphyseal plates
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
Stages of Endochondral Ossification
Secondary
ossificaton
center
Deteriorating
cartilage
matrix
Hyaline
cartilage
Primary
ossification
center
Spongy
bone
formation
Epiphyseal
blood vessel
Medullary
cavity
Articular
cartilage
Spongy
bone
Epiphyseal
plate
cartilage
Bone collar
1 Formation of
bone collar
around hyaline
cartilage model.
Blood
vessel of
periosteal
bud
2 Cavitation of
the hyaline cartilage within the
cartilage model.
Calcification of cartilage
3 Invasion of
internal cavities
by the periosteal
bud and spongy
bone formation.
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4 Formation of the
medullary cavity as
ossification continues;
appearance of secondary ossification
centers in the epiphyses in preparation
for stage 5.
5 Ossification of the
epiphyses; when
completed, hyaline
cartilage remains only
in the epiphyseal plates
and articular cartilages.
Figure 6.8
Postnatal Bone Growth
Growth in length of long bones
Cartilage on the side of the epiphyseal plate closest
to the epiphysis is relatively inactive
Cartilage abutting the shaft of the bone organizes
into a pattern that allows fast, efficient growth
Cells of the epiphyseal plate proximal to the resting
cartilage form three functionally different zones:
growth, transformation, and osteogenic (see slide
20)
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Details of Stages of Endochondral Ossification
1) Bone collar forms around the diaphysis of the
hyaline cartilage model
Osteoblasts of the converted periosteum secrete
osteoid against the hyaline cartilage diaphysis
encasing it in a bone collar
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Details of Stages of Endochondral Ossification
2) cartilage in the center of the diaphysis calcifies
and then cavitates
Chondrocytes w/I the shaft hypertrophy &
signal surrounding cartilage matrix to calcify.
Chondrocytes die due to lack of nutrients
(impermeability of calcified matrix)
Matrix deteriorates thus opening up cavities
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Details of Stages of Endochondral Ossification
3) Periosteal bud invades the internal cavities and spongy
bone forms
The forming cavities are invaded by a collection of
elements
Periosteal bud contains a nutrient artery and vein,
lymphatics, nerve fibers, red marrow elements,
osteoblasts, and osteoclasts
Osteoclasts erode the calcified cartilage matrix &
osteoblasts secrete osteoid around the remaining hyaline
cartilage forming bone-covered cartilage trabuculae (the
formation of spongy bone)
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Details of Stages of Endochondral Ossification
4) The diaphysis elongates and a medullary cavity
forms
Osteoclasts open up a medullary cavity by
breaking down the newly formed spongy bone
Cartilage is growing, bones being calcified and
eroded and then replaced by bony spicules on
the epiphyseal surfaces facing the medullary
cavity
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Details of Stages of Endochondral Ossification
5) The epiphysis ossify
Secondary ossification centers appear in one or
both epiphyses.
Steps 1-4 occur there except no medullary
cavity forms
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Details of Stages of Endochondral Ossification
Finally, hyaline cartilage remains at:
Epiphyseal surface (articular cartilage)
Epiphyseal plates (junction of the diaphysis and
the epiphysis)
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Functional Zones in Long Bone Growth
Growth zone – cartilage cells undergo mitosis,
pushing the epiphysis away from the diaphysis
Transformation zone – older cartilage cells
enlarge, the matrix becomes calcified, cartilage
cells die, and the matrix begins to deteriorate
Osteogenic zone – new bone formation occurs
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
Postnatal Bone Growth
Long bones lengthen by interstial growth of the
epiphyseal plates, and increase thickness by
appositional growth (cells in the perichondrium
secrete matrix against the external face of existing
cartilage)
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Long Bone Growth and Remodeling
Growth occurs at the epiphyseal plate (the cartilage
abutting the diaphysis) called the Growth Zone
Cartilage cells stack and divide quickly pushing the
epiphysis away from the diaphysis causing bone to
lengthen
The older chondrocytes die & deteriorate forming the
Calcification Zone
The resulting calcified spicules become part of the
Ossification Zone and are invaded by marrow elements
from the medullary cavity
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Growth in Length of Long Bone
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Figure 6.9
Long Bone Growth and Remodeling
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Figure 6.10
Long Bone Growth and Remodeling
Longitudinal growth is accompanied by
remodelling which includes appositional growth to
thicken bone
Includes bone formation & reabsorption
Bone growth stops around age 21 for males and 18
for females when the epiphysis & diaphysis fuse
(epiphyseal plate closure)
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Long Bone Growth and Remodeling
Growth in width (thickness) via appositional
growth
Osteoblasts beneath the periosteum secrete bone
matrix on the external bone surface as osteoclasts
on the endosteal surface of the dyaphysis remove
bone
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Hormonal Regulation of Bone Growth During
Youth
During infancy and childhood, epiphyseal plate
activity is stimulated by growth hormone (released
by the anterior pituitary)
During puberty, testosterone and estrogens:
Initially promote adolescent growth spurts
Cause masculinization and feminization of specific
parts of the skeleton
Later induce epiphyseal plate closure, ending
longitudinal bone growth
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Bone Deposition
Occurs where bone is injured or added strength is
needed
Requires a diet rich in protein, vitamins C, D, and
A, calcium, phosphorus, magnesium, and
manganese
Alkaline phosphatase is essential for
mineralization of bone
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Bone Deposition
Sites of new matrix deposition are revealed by the:
Osteoid seam – unmineralized band of bone matrix
Calcification front – abrupt transition zone between
the osteoid seam and the older mineralized bone
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Bone Resorption
Accomplished by osteoclasts (giant, multinucleated cells that
arise from the same stem cells that produce macrophages)
Resorption bays – grooves formed by osteoclasts as they break
down bone matrix
The osteoclast membrane seals off the bone that is to be broken
down
Resorption involves osteoclast secretion of:
Lysosomal enzymes that digest organic matrix
Hydrochloric acid that converts calcium salts into soluble
forms
The broken down products are endocytosed (transcytosed)
and released into the interstitial fluid and blood
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Osteoclasts
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Control of Remodeling
Two control loops regulate bone remodeling
Hormonal mechanism maintains calcium
homeostasis in the blood (negative feedback)
Mechanical and gravitational forces acting on the
skeleton
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Hormonal Mechanism
Rising blood Ca2+ levels trigger the thyroid to
release calcitonin
Calcitonin inhibits bone resorption and stimulates
calcium salt deposit in bone
Falling blood Ca2+ levels signal the parathyroid
glands to release parathyroid hormone (PTH)
PTH signals osteoclasts to degrade bone matrix
and release Ca2+ into the blood
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Hormonal Control of Blood Ca
Rising blood
Ca2+ levels
Imb
ala
nce
Calcium homeostasis of blood: 9–11 mg/100 ml
Imb
ala
nce
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
Figure 6.11
Hormonal Control of Blood Ca
Thyroid
gland
Rising blood
Ca2+ levels
Imb
ala
nce
Calcium homeostasis of blood: 9–11 mg/100 ml
Imb
ala
nce
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
Figure 6.11
Hormonal Control of Blood Ca
Calcitonin
secreted
Thyroid
gland
Rising blood
Ca2+ levels
Imb
ala
nce
Calcium homeostasis of blood: 9–11 mg/100 ml
Imb
ala
nce
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
Figure 6.11
Hormonal Control of Blood Ca
Calcitonin
secreted
Calcitonin
stimulates
calcium salt
deposit
in bone
Thyroid
gland
Rising blood
Ca2+ levels
Imb
ala
nce
Calcium homeostasis of blood: 9–11 mg/100 ml
Imb
ala
nce
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
Figure 6.11
Hormonal Control of Blood Ca
Calcitonin
secreted
Calcitonin
stimulates
calcium salt
deposit
in bone
Thyroid
gland
Rising blood
Ca2+ levels
Calcium homeostasis of blood: 9–11 mg/100 ml
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
Figure 6.11
Hormonal Control of Blood Ca
Imb
ala
nce
Calcium homeostasis of blood: 9–11 mg/100 ml
Imb
ala
nce
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
Falling blood
Ca2+ levels
Figure 6.11
Hormonal Control of Blood Ca
Imb
ala
nce
Calcium homeostasis of blood: 9–11 mg/100 ml
Imb
ala
nce
Falling blood
Ca2+ levels
Thyroid
gland
Parathyroid
glands
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
Parathyroid
glands release
parathyroid
hormone (PTH)
Figure 6.11
Hormonal Control of Blood Ca
Imb
ala
nce
Calcium homeostasis of blood: 9–11 mg/100 ml
Imb
ala
nce
Falling blood
Ca2+ levels
Thyroid
gland
Parathyroid
glands
Parathyroid
glands release
parathyroid
hormone (PTH)
PTH
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
Figure 6.11
Hormonal Control of Blood Ca
Imb
ala
nce
Calcium homeostasis of blood: 9–11 mg/100 ml
Imb
ala
nce
Falling blood
Ca2+ levels
Thyroid
gland
Osteoclasts
degrade bone
matrix and release
Ca2+ into blood
Parathyroid
glands
Parathyroid
glands release
parathyroid
hormone (PTH)
PTH
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
Figure 6.11
Hormonal Control of Blood Ca
Calcium homeostasis of blood: 9–11 mg/100 ml
Falling blood
Ca2+ levels
Thyroid
gland
Osteoclasts
degrade bone
matrix and release
Ca2+ into blood
Parathyroid
glands
Parathyroid
glands release
parathyroid
hormone (PTH)
PTH
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
Figure 6.11
Hormonal Control of Blood Ca
Calcitonin
secreted
Calcitonin
stimulates
calcium salt
deposit
in bone
Thyroid
gland
Rising blood
Ca2+ levels
Imb
ala
nc
e
Calcium homeostasis of blood: 9–11 mg/100 ml
Imb
ala
nc
e
Falling blood
Ca2+ levels
Thyroid
gland
Osteoclasts
degrade bone
matrix and release
Ca2+ into blood
Parathyroid
glands
PTH
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
Parathyroid
glands release
parathyroid
hormone (PTH)
Figure 6.11
Response to Mechanical Stress
Mechanical stress = pull of muscles and gravity
Keeps bone strong when stresses are acting
Loading bends bone, compressing one side and
stretching the other side
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Response to Mechanical Stress
Wolff’s law – a bone grows or remodels in
response to the forces or demands placed upon it
Observations supporting Wolff’s law include
Long bones are thickest midway along the shaft
(where bending stress is greatest)
Curved bones are thickest where they are most
likely to buckle
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Response to Mechanical Stress
Trabeculae of spongy bone form trusses / struts
along lines of stress / compression
Large, bony projections occur where heavy, active
muscles attach
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Bone Fractures (Breaks)
Bone fractures are classified by:
Position of the bone ends after fracture
Nondisplaced: retain normal postion
Displaced: out of normal position
Completeness of the break
Complete fracture: bone is broken thru
Incomplete fracture: bone is Not broken thru
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Bone Fractures (Breaks)
The orientation of the break to the long axis of the
bone
Linear: parallels the long axis
Transverse: perpendicular to the long axis
Penetration of the skin
Compound (open) fracture: yes
Simple (closed) fracture: no
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Common Types of Fractures
Comminuted – bone fragments into three or more
pieces; common in the elderly
Spiral – ragged break when bone is excessively
twisted; common sports injury
Depressed – broken bone portion pressed inward;
typical skull fracture
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Common Types of Fractures
Compression – bone is crushed; common in porous
bones
Epiphyseal – epiphysis separates from diaphysis
along epiphyseal line; occurs where cartilage cells
are dying
Greenstick – incomplete fracture where one side of
the bone breaks and the other side bends; common
in children
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Common Types of Fractures
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Table 6.2.1
Common Types of Fractures
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Table 6.2.2
Common Types of Fractures
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Table 6.2.3
Stages in the Healing of a Bone Fracture
Fractures are treated by
Reduction: the realignment of the broken ends
Immobilization via cast or traction
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Stages in the Healing of a Bone Fracture
Hematoma formation
Torn blood vessels
hemorrhage
A mass of clotted
blood (hematoma)
forms at the fracture
site
Site becomes swollen,
painful, and inflamed
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Figure 6.13.1
Stages in the Healing of a Bone Fracture
Fibrocartilaginous callus
forms
Granulation tissue (soft
callus) forms a few days
after the fracture
Capillaries grow into the
tissue and phagocytic
cells begin cleaning
debris
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
Figure 6.13.2
Stages in the Healing of a Bone Fracture
The fibrocartilaginous callus forms when:
Osteoblasts and fibroblasts migrate to the fracture and begin
reconstructing the bone
Fibroblasts secrete collagen fibers that connect broken bone
ends
Some fibroblasts differentiate into chondroblasts and
secrete cartilage matrix
Osteoblasts begin forming spongy bone
Osteoblasts furthest from capillaries secrete an externally
bulging cartilaginous matrix that later calcifies
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Stages in the Healing of a Bone Fracture
Bony callus formation
New bone trabeculae
appear in the
fibrocartilaginous callus
Fibrocartilaginous callus
converts into a bony (hard)
callus
Bone callus begins 3-4
weeks after injury, and
continues until firm union
is formed 2-3 months later
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Figure 6.13.3
Stages in the Healing of a Bone Fracture
Bone remodeling
Excess material on the
bone shaft exterior and
in the medullary canal
is removed
Compact bone is laid
down to reconstruct
shaft walls
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Figure 6.13.4
Homeostatic Imbalances of Bone
Osteomalacia
Bones are inadequately mineralized (Ca++ salts not
deposited) causing softened, weakened bones
Main symptom is pain when weight is put on the
affected bone
Caused by insufficient calcium in the diet, or by
vitamin D deficiency
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Homeostatic Imbalances
Rickets
Bones of children are inadequately mineralized causing
softened, weakened bones
Because the epiphyseal plates can not be calcified, they
continue to widen and the ends of long bones become
visibly enlarged and abnormally long
Bowed legs and deformities of the pelvis, skull, and rib
cage are common
Caused by insufficient calcium in the diet, or by vitamin D
deficiency
Sunlight spurs body to make vitamin D
Milk w/ vitamin D and sunlight cure the disorders
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Homeostatic Imbalances
Osteoporosis
Group of diseases in which bone reabsorption
outpaces bone deposit
Spongy bone of the spine and the neck of the femur
are most vulnerable
Occurs most often in postmenopausal women
Bones become very fragile
Matrix composition is the same, but bone mass is
reduced and bones become porous and light
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Osteoporosis: Treatment
Calcium and vitamin D supplements
Increased weight-bearing exercise
Hormone (estrogen) replacement therapy (HRT)
slows bone loss by restraining osteoclast activity
and promoting new bone deposit (but HRT comes
at a price…health risk: stroke, heart disease, breast
cancer)
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Paget’s Disease
Characterized by excessive and haphazard bone
formation and breakdown
Pagetic bone with an excessively high ratio of
spongy bone to compact bone is formed
Osteoclast activity wanes, but osteoblast activity
continues to work forming irregular bone
thickening and filling in marrow cavity
Pagetic bone, along with reduced mineralization,
causes spotty weakening of bone usually at the
spine, pelvis, femur, and skull
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