Bone Formation and Development

Skeletal System
Bone Formation
1
Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings
INTRODUCTION
 Bone is made up of several different tissues working

together: bone, cartilage, dense connective tissue,
epithelium, various blood forming tissues, adipose
tissue, and nervous tissue.
 Each individual bone is an organ; the bones, along
with their cartilages, make up the skeletal system.
2
The Skeletal System: Bone Tissue
 Dynamic and ever-changing throughout life

 Skeleton composed of many different tissues
 cartilage, bone tissue, epithelium, nerve, blood forming tissue, adipose,
and dense connective tissue
3
Functions of Bone
 Supporting & protecting soft tissues

 Attachment site for muscles making
movement possible
 Storage of the minerals, calcium &
phosphate -- mineral homeostasis
 Blood cell production occurs in red bone
marrow (hemopoiesis)
 Energy storage
4
in yellow bone marrow
Importance of Ionic Calcium in the Body
 Calcium is necessary for:

 Transmission of nerve impulses
 Muscle contraction
 Blood coagulation
 Secretion by glands and nerve cells
 Cell division

Anatomy of a Long Bone
 diaphysis = shaft
 epiphysis = one end of a
long bone
 metaphyses are the areas
between the epiphysis and
diaphysis and include the
epiphyseal plate in
growing bones.
 Articular cartilage over

joint surfaces acts as
friction reducer & shock
absorber
 Medullary cavity = marrow
cavity
6
Anatomy of a Long Bone
 Endosteum = lining of
marrow cavity
 Periosteum = tough
membrane covering bone
but not the cartilage
 fibrous layer = dense
irregular CT
 osteogenic layer = bone
cells & blood vessels
that nourish or help
with repairs

7
Histology of Bone
 A type of connective tissue as seen

by widely spaced cells separated by
matrix
 Matrix of 25% water, 25% collagen
fibers & 50% crystalized mineral
salts
 4 types of cells in bone tissue

8
HISTOLOGY OF BONE TISSUE
 Bone (osseous) tissue consists of widely separated cells
surrounded by large amounts of matrix.
 The matrix of bone contains inorganic salts, primarily
hydroxyapatite and some calcium carbonate, and
collagen fibers.
 These and a few other salts are deposited in a
framework of collagen fibers, a process called
calcification or mineralization.
 The process of calcification occurs only in the
presence of collagen fibers.
 Mineral salts confer hardness on bone while collagen
fibers give bone its great9 tensile strength.
Bone Cells
1. Osteogenic cells undergo cell division and develop

into osteoblasts.
2. Osteoblasts are bone-building cells.
3. Osteocytes are mature bone cells and the principal
cells of bone tissue.
4. Osteoclasts are derived from monocytes and serve
to break down bone tissue.
10
Cells of Bone
 Osteoprogenitor cells ---- undifferentiated cells

 can divide to replace themselves & can become osteoblasts
 found in inner layer of periosteum and endosteum
 Osteoblasts--form matrix & collagen fibers but can’t divide
 Osteocytes ---mature cells that no longer secrete matrix
 Osteoclasts---- huge cells from fused monocytes (WBC)
 function in bone resorption at surfaces such as endosteum
11
Osteoblasts Osteocytes Osteoclasts

12
Matrix of Bone
 Inorganic mineral salts provide bone’s hardness
 hydroxyapatite (calcium phosphate) & calcium carbonate
 Organic collagen fibers provide bone’s flexibility
 their tensile strength resists being stretched or torn
 remove minerals with acid & rubbery structure results
 Bone is not completely solid since it has small spaces for
vessels and red bone marrow
 spongy bone has many such spaces
 compact bone has very few
13
such spaces
Compact Bone
 Compact bone is arranged in units called osteons or

Haversian systems .
 Osteons contain blood vessels, lymphatic vessels,
nerves, and osteocytes along with the calcified
matrix.
 Osteons are aligned in the same direction along lines
of stress. These lines can slowly change as the
stresses on the bone changes.
14
Compact or
Dense Bone
 Looks like solid hard layer of bone

 Makes up the shaft of long bones and the external
layer of all bones
 Resists stresses produced by weight and movement
15
Histology of Compact Bone
 Osteon is concentric rings (lamellae) of calcified matrix
surrounding a vertically oriented blood vessel
 Osteocytes are found in spaces called lacunae
 Osteocytes communicate through canaliculi filled with
extracellular fluid that connect one cell to the next cell
 Interstitial lamellae represent older osteons that have been
partially removed during tissue remodeling

16
Spongy Bone
 Spongy (cancellous) bone does not contain osteons.

It consists of trabeculae surrounding many red
marrow filled spaces.
 It forms most of the structure of short, flat, and
irregular bones, and the epiphyses of long bones.
 Spongy bone tissue is light and supports and protects
the red bone marrow.
17
The Trabeculae of Spongy Bone
 Latticework of thin plates of bone called trabeculae oriented along lines of

stress
 Spaces in between these struts are filled with red marrow where blood cells
develop
 Found in ends of long bones and inside flat bones such as the hipbones,
sternum, sides of skull, and ribs.
Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings No true Osteons. 18
Blood and Nerve Supply of Bone
 Periosteal arteries
 supply periosteum
 Nutrient arteries
 enter through nutrient
foramen
 supplies compact bone of
diaphysis & red marrow
 Metaphyseal & epiphyseal
aa.
 supply red marrow &
bone tissue of epiphyses
19
BONE FORMATION
 All embryonic connective tissue begins as
mesenchyme.
 Bone formation is termed osteogenesis or
ossification and begins when mesenchymal cells
provide the template for subsequent ossification.
 Two types of ossification occur.
 Intramembranous ossification is the formation of
bone directly from or within fibrous connective
tissue membranes.
 Endochondrial ossification is the formation of bone
from hyaline cartilage models.
20
Stages of Intramembranous Ossification
 Forms some flat bones of the skull, mandible, and clavicle.

 An ossification center appears in the fibrous connective tissue
membrane
 Bone matrix is secreted within the fibrous membrane
 The matrix surrounds the cell and then calcifies as the
osteoblast becomes an osteocyte.
 The calcifying matrix centers join to form bridges of
trabeculae that constitute spongy bone with red marrow
between.
 On the periphery the mesenchyme condenses and develops
into woven bone and the periosteum.

Figure 6.7.1
Figure 6.7.2
Figure 6.7.3
Figure 6.7.4
Endochondral Ossification
 Endochondrial ossification involves replacement of
cartilage by bone and forms most of the bones of the
body
 The first step in endochondrial ossification is the
development of the cartilage model.
 Begins in the second month of development
 Uses hyaline cartilage “bones” as models for bone
construction
 Requires breakdown of hyaline cartilage prior to
ossification
27
Endochondral Bone Formation
 Development of Cartilage model

 Mesenchymal cells form a cartilage
model of the bone during
development
 Growth of Cartilage model
 in length by chondrocyte cell division
and matrix formation ( interstitial
growth)
 in width by formation of new matrix
on the periphery by new
chondroblasts from the perichondrium
(appositional growth)

28
Stages of Endochondral Ossification
 Formation of bone collar

 Cavitation of the hyaline: cartilage cells in mid-
region burst and change pH triggering calcification
and chondrocyte death
 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
Stages of Endochondral Ossification cont.
 Development of Primary Ossification

Center
 perichondrium lays down
periosteal bone collar
 nutrient artery penetrates center of
cartilage model
 periosteal bud brings osteoblasts
and osteoclasts to center of
cartilage model
 osteoblasts deposit bone matrix
over calcified cartilage forming
spongy bone trabeculae
30
 © 2004 Pearson Education,form
Copyrightosteoclasts medullary
Inc., publishing cavity
as Benjamin Cummings
Stages of Endochondral Ossification Cont.
 Development of Secondary Ossification Center

 blood vessels enter the epiphyses around time of birth
 spongy bone is formed but no medullary cavity
 Formation of Articular Cartilage
 cartilage on ends of bone remains as articular cartilage.
31
Stages of Endochondral Ossification
Secondary Articular
ossification cartilage
center
Epiphyseal Spongy
Deteriorating blood vessel bone
Hyaline cartilage matrix
cartilage
Spongy Epiphyseal
bone plate
Primary
formation Medullary cartilage
ossification
center cavity
Bone Blood
collar vessel of
periostea
l bud
1 Formation
of bone 2 Cavitation
collar of the 3 Invasion of
around hyaline internal cavities 4 Formation of the
hyaline cartilage by the medullary cavity as 5 Ossification of the
cartilage within the periosteal bud ossification continues; epiphyses; when
model. cartilage and spongy appearance of completed, hyaline
model. bone formation. secondary ossification cartilage remains
centers in the only in the
epiphyses in epiphyseal plates
preparation for stage 5. and articular
cartilages
Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Figure 6.8
Postnatal Bone Growth- Timeline
 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

Long Bone Growth and Remodeling
Appositional Growth of Bone
Central canal of osteon
Periosteal ridge
Artery Periosteum Penetrating canal
1 Osteoblasts beneath 2 As the bony ridges 3 The periosteum 4 As the osteoblasts

the periosteum enlarge and meet, lining the tunnel is beneath the endosteum
secrete bone matrix, the groove transformed into an form new lamellae, a new
forming ridges that containing the endosteum and the osteon is created.
follow the course of blood vessel osteoblasts just Meanwhile new
periosteal blood becomes a tunnel. deep to the tunnel circumferential lamellae
vessels. endosteum secrete are elaborated beneath
bone matrix, the periosteum and the
narrowing the canal. process is repeated,
continuing to enlarge
bone diameter.
Factors Affecting Bone Growth
 Nutrition
 adequate levels of minerals and vitamins
 calcium and phosphorus for bone growth
 vitamin C for collagen formation
 vitamins K and B12 for protein synthesis
 Sufficient levels of specific hormones
 during childhood need insulinlike growth factor
 promotes cell division at epiphyseal plate
 need hGH (growth), thyroid (T3 &T4) and insulin
 sex steroids at puberty
 At puberty the sex hormones, estrogen and testosterone, stimulate sudden
growth and modifications of the skeleton to create the male and female
forms. 36
Factors that affect Bone Growth
 EXERCISE: Within limits, bone has the ability to alter its

strength in response to mechanical stress by increasing deposition
of mineral salts and production of collagen fibers.
 Removal of mechanical stress leads to weakening of bone
through demineralization (loss of bone minerals) and collagen
reduction.
 reduced activity while in a cast
 astronauts in weightless environment
 bedridden person
 Weight-bearing activities, such as walking or moderate
weightlifting, help build and retain bone mass.
37
Bone Remodeling
 Remodeling units – adjacent osteoblasts and

osteoclasts deposit and resorb bone at periosteal and
endosteal surfaces

Bone Remodeling
 Remodeling is the ongoing replacement of old bone

tissue by new bone tissue.
 Old bone is constantly destroyed by osteoclasts,
whereas new bone is constructed by osteoblasts.
 In orthodontics teeth are moved by braces. This
places stress on bone in the sockets causing
osteoclasts and osteoblasts to remodel the sockets
so that the teeth can be properly aligned
 Several hormones and calcitriol control bone
growth and bone remodeling
39
Bone Remodeling
 Ongoing since osteoclasts carve out small tunnels and

osteoblasts rebuild osteons.
 osteoclasts form leak-proof seal around cell edges
 secrete enzymes and acids beneath themselves
 release calcium and phosphorus into interstitial fluid
 osteoblasts take over bone rebuilding
 Continual redistribution of bone matrix along lines of
mechanical stress
 distal femur is fully remodeled every 4 months
40
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
 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
Bone Resorption
 Accomplished by osteoclasts
 Resorption bays – grooves formed by osteoclasts as
they break down bone matrix
 Resorption involves osteoclast secretion of:
 Lysosomal enzymes that digest organic matrix
 Acids that convert calcium salts into soluble forms
 Dissolved matrix is transcytosed across the
osteoclast’s cell where it is secreted into the
interstitial fluid and then into the blood
Hormonal Regulation of Bone Growth During
Youth
 During infancy and childhood, epiphyseal plate

activity is stimulated by growth hormone
 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
Control of Remodeling
 Two control loops regulate bone remodeling

 Hormonal mechanism maintains calcium
homeostasis in the blood
 Mechanical and gravitational forces acting on the
skeleton

Hormonal Mechanism
 Rising blood Ca2+ levels trigger the thyroid to

release calcitonin
 Calcitonin stimulates calcium salt deposit in bone
 Falling blood Ca2+ levels signal the parathyroid
glands to release PTH
 PTH signals osteoclasts to degrade bone matrix and
release Ca2+ into the blood

Hormonal Mechanism
Hormonal Mechanism
 Parathyroid hormone (PTH) is secreted if

Ca+2 levels falls
 PTH gene is turned on & more PTH is
secreted from gland
 osteoclast activity increased, kidney
retains Ca+2 and produces calcitriol
 Calcitonin hormone is secreted from
parafollicular cells in thyroid if Ca+2 blood
levels get too high
 inhibits osteoclast activity
 increases bone formation by osteoblasts

47
Calcium Homeostasis & Bone Tissue
 Skeleton is a reservoir of Calcium & Phosphate
 Calcium ions involved with many body systems
 nerve & muscle cell function
 blood clotting
 enzyme function in many biochemical reactions
 Small changes in blood levels of Ca+2 can be deadly
(plasma level maintained 9-11mg/100mL)
 cardiac arrest if too high
 respiratory arrest if too48low
Development of Bone Tissue
 Both types of bone formation begin with

mesenchymal cells
 Mesenchymal cells transform into

chondroblasts which form cartilage
OR
 Mesenchymal cells become osteoblasts

which form bone
Mesenchymal Cells

49
Developmental Aspects of Bones
 Mesoderm gives rise to embryonic mesenchymal

cells, which produce membranes and cartilages that
form the embryonic skeleton
 The embryonic skeleton ossifies in a predictable
timetable that allows fetal age to be easily
determined from sonograms
 At birth, most long bones are well ossified (except
for their epiphyses)

Developmental Aspects of Bone Tissue
5th Week =limb bud appears as mesoderm

covered with ectoderm
6th Week = constriction produces hand or
foot plate
and skeleton now totally cartilaginous
7th Week = endochondral ossification
begins
8th Week = upper & lower limbs
appropriately named

51
AGING AND BONE TISSUE
 By age 25, nearly all bones are completely ossified

 A single gene that codes for vitamin D docking
determines both the tendency to accumulate bone
mass early in life, and the risk for osteoporosis later
in life

AGING AND BONE TISSUE
 In old age, bone resorption predominates
 Of two principal effects of aging on bone, the first is the loss of
calcium and other minerals from bone matrix (demineralization),
which may result in osteoporosis.
 very rapid in women 40-45 as estrogens levels decrease
 in males, begins after age 60
 The second principal effect of aging on the skeletal system is a
decreased rate of protein synthesis
 decrease in collagen production which gives bone its tensile
strength
 decrease in growth hormone
 bone becomes brittle & susceptible
53 to fracture

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Skeletal System

 Bone is made up of several different tissues working

 Dynamic and ever-changing throughout life

 Supporting & protecting soft tissues

 Calcium is necessary for:

Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings

 Articular cartilage over

Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings

 A type of connective tissue as seen

Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings

1. Osteogenic cells undergo cell division and develop

 Osteoprogenitor cells ---- undifferentiated cells

Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings

 Compact bone is arranged in units called osteons or

 Looks like solid hard layer of bone

Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings

 Spongy (cancellous) bone does not contain osteons.

 Latticework of thin plates of bone called trabeculae oriented along lines of

 Forms some flat bones of the skull, mandible, and clavicle.

Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings

 Development of Cartilage model

Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings

 Formation of bone collar

 Development of Primary Ossification

 Development of Secondary Ossification Center

 Growth in length of long bones

Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings

Artery Periosteum Penetrating canal

1 Osteoblasts beneath 2 As the bony ridges 3 The periosteum 4 As the osteoblasts

 EXERCISE: Within limits, bone has the ability to alter its

 Remodeling units – adjacent osteoblasts and

Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings

 Remodeling is the ongoing replacement of old bone

 Ongoing since osteoclasts carve out small tunnels and

 Occurs where bone is injured or added strength is

 During infancy and childhood, epiphyseal plate

 Two control loops regulate bone remodeling

Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings

 Rising blood Ca2+ levels trigger the thyroid to

Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings

 Parathyroid hormone (PTH) is secreted if

Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings

 Both types of bone formation begin with

 Mesenchymal cells transform into

 Mesenchymal cells become osteoblasts

Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings

 Mesoderm gives rise to embryonic mesenchymal

Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings

5th Week =limb bud appears as mesoderm

Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings

 By age 25, nearly all bones are completely ossified

Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings

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