Chapter 07

Lecture Outline
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 Introduction

In this chapter we will cover:

Bone tissue composition
How bone functions, develops, and
grows
How bone metabolism is regulated and
some of its disorders
 Introduction
Bones and teeth are the most durable
remains of a once-living body
Living skeleton is made of dynamic
tissues, full of cells, permeated with
nerves and blood vessels
Continually remodels itself and
interacts with other organ systems of
the body
Osteology is the study of bone
Tissues and Organs of the
Skeletal System

Expected Learning Outcomes

Name the tissues and organs that compose the
skeletal system.
State several functions of the skeletal system.
Distinguish between bones as a tissue and as
an organ.
Describe the four types of bones classified by
shape.
Describe the general features of a long bone
and a flat bone.
 Tissues and Organs of the
Skeletal System

Skeletal system—composed of
bones, cartilages, and ligaments
Cartilage—forerunner of most bones
Covers many joint surfaces of mature
bone
Ligaments—hold bones together at
joints
Tendons—attach muscle to bone
 Functions of the Skeleton
Support—limb bones and vertebrae support body;
jaw bones support teeth; some bones support
viscera
Protection—of brain, spinal cord, heart, lungs, and
more
Movement—limb movements, breathing, and other
movements depend on bone
Electrolyte balance—calcium and phosphate
levels
Acid–base balance—buffers blood against large pH
changes by altering phosphate and carbonate salt
levels
Blood formation—red bone marrow is the chief
producer of blood cells
 Bones and Osseous Tissue
Bone (osseous tissue)—connective
tissue with the matrix hardened by
calcium phosphate and other minerals

Mineralization or calcification—the
hardening process of bone

Individual bones (organs) consist of

bone tissue, bone marrow, cartilage,
adipose tissue, nervous tissue, and
fibrous connective tissue
 General Features of Bones
Flat bones
Thin, curved plates
Protect soft organs
Long bones
Longer than wide
Rigid levers acted upon by muscles; crucial for
movement
Short bones
Approximately equal in length and width
Glide across one another in multiple directions
Irregular bones
Elaborate shapes that do not fit into other
categories
 General Features of Bones
Compact bone—dense outer shell of bone
Spongy (cancellous) bone—loosely organized
bone tissue
Found in center of ends and center of shafts of long
bones and in middle of nearly all others
Covered by more durable compact bone
Skeleton three-fourths compact and one-
fourth spongy bone by weight
Long bone features
Diaphysis—shaft that provides leverage
Medullary cavity (marrow cavity)—space in the
diaphysis of a long bone that contains bone marrow
Epiphyses—enlarged ends of a long bone
Strengthen joint and anchor ligaments and tendons
 General Features of Bones

Articular cartilage—layer of hyaline cartilage that

covers joint surface; allows joint to move more freely
Nutrient foramina—minute holes in bone surface
that allows blood vessels to penetrate
Periosteum—external sheath covering most of bone
Outer fibrous layer of collagen
Some fibers continuous with tendons
Perforating fibers—penetrate into bone matrix
Inner osteogenic layer of bone-forming cells
Important to bone growth and healing of fractures
Endosteum—thin layer of reticular connective tissue
lining marrow cavity
Has cells that dissolve osseous tissue and others that
deposit it
 General Features of Bones

Epiphyseal plate (growth plate)—area of

hyaline cartilage that separates epiphyses and
diaphyses of children’s bones
Enables growth in length
Epiphyseal line—in adults, a bony scar that marks
where growth plate used to be
 General Features of Bones
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Arti
cula
Long bone
r

Epiphyses and
cart Epip
ilag hysis
e
Red
bon
e
Epiph
marr
diaphysis
yseal
ow
line
Marrow
cavity

Yellow bone Compact and

marrow

Perios
teum
spongy bone
Nutrient
Diap
Marrow cavity
foramen
hysis

Site of
endosteum
Articular
Compact
bone cartilage
Spongy
bone
Epiph
yseal
line Epip
Periosteum
hysis
Arti
cula
r (a) (b)
cart Livi Dri
ilag
e
ng Figure ed
 General Features of Bones
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction
or display.
Flat bone
Sandwich-like
construction
Two layers of
Su
tu compact bone
re
enclosing a middle
Outer
compact
bone

Spongy
layer of spongy bone
bone
(diploe) Both surfaces covered
with periosteum
Trabe
culae
Diploe—spongy middle
Inner
layer
compact
bone Absorbs shock
Figure Marrow spaces lined
7.2 with endosteum
Histology of Osseous Tissue
Expected Learning Outcomes
List and describe the cells, fibers, and ground
substance of bone tissue.
State the importance of each constituent of
bone tissue.
Compare the histology of the two types of
bone tissue.
Distinguish between the two types of bone
marrow.
 Bone Cells
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Osteogeni Osteo Osteo

c cell blast cyte

Rough Secre
endopla tory
smic vesicl
reticulu es
Nuc
m Mitochon
leus drion

(a) Osteocyte
development
Figure
7.3a

Bone is connective tissue that consists of cells,

fibers, and ground substance

Four principal types of bone cells

Osteogenic cells; osteoblasts; osteocytes;
osteoclasts
 Bone Cells
Osteogenic cells—stem cells found in endosteum and
inner layer of periosteum
Arise from embryonic mesenchymal cells
Multiply continuously and give rise to most other bone cell
types

Osteoblasts—bone-forming cells
Form single layer of cells under endosteum and periosteum
Nonmitotic
Synthesize soft organic matter of matrix which then hardens
by mineral deposition
Stress stimulates osteogenic cells to multiply rapidly and
increase the number of osteoblasts which reinforce bone
Secrete hormone osteocalcin
Stimulates insulin secretion of pancreas
Increases insulin sensitivity in adipocytes which limits the growth
of adipose tissue
 Bone Cells

Osteocytes—former osteoblasts that have become

trapped in the matrix they deposited
Lacunae—tiny cavities where osteocytes reside
Canaliculi—little channels that connect lacunae
Cytoplasmic processes of osteocytes reach into canaliculi and
contact processes of neighboring cells
Gap junctions allow for passage of nutrients, wastes, signals
Some osteocytes reabsorb bone matrix while others deposit it
Act as strain sensors—when stressed, produce biochemical
signals that regulate bone remodeling (shape and density
changes that are adaptive)
 Bone Cells
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Oste
ocyte
Osteo Oss
clast eou
Stem s
Perios Resor
cells tiss
teum ption
N bay
ue
uc
Osteo
lei
Fu clast
sio
n Ruf
Lysoso
fle
mes
d
bo
(b) Osteoclast rd
development er
Figure
7.3b

Osteoclasts—bone-dissolving cells found on bone

surface
Osteoclasts develop from same bone marrow stem cells
that give rise to blood cells (different origin from other
bone cells)
Very large cells formed from fusion of several stem cells
Have multiple nuclei in each cell
Ruffled border (large surface area) faces bone
Cells often reside in resorption bays (pits in bone
surface)
Dissolving bone is part of bone remodeling
 The Matrix

Matrix of osseous tissue is, by dry weight,

about one-third organic and two-thirds inorganic
matter

Organic matter—synthesized by osteoblasts

Collagen, carbohydrate–protein complexes, such as
glycosaminoglycans, proteoglycans, and glycoproteins

Inorganic matter
85% hydroxyapatite (crystallized calcium phosphate
salt)
10% calcium carbonate
Other minerals (fluoride, sodium, potassium,
magnesium)
 The Matrix

Bone is a composite material—a combination of

a ceramic and a polymer
Hydroxyapatite and other minerals are the ceramic and
collagen (protein) is the polymer
Ceramic portion allows the bone to support body weight
without sagging
Rickets is a disease caused by mineral deficiency and
resulting in soft, deformed bones
Polymer (protein) gives some flexibility
Osteogenesis imperfecta (brittle bone disease) results
from a defect in collagen deposition
Histology of Osseous Tissue

Figure
7.4a,c,d
 Compact bone
Histology of compact
bone reveals
osteons (haversian
systems)
Concentric lamellae
surround a central
(haversian) canal
running longitudinally
Perforating
(Volkmann) canals—
transverse or diagonal
passages
Circumferential
lamellae fill outer
region of dense bone
Interstitial lamellae
fill irregular regions
Figure between osteons
7.4b,c,d
 Spongy Bone

Spongy bone consists of:

Lattice of bone covered with endosteum
Slivers of bone called spicules
Thin plates of bone called trabeculae
Spaces filled with red bone marrow

Few osteons and no central canals

All osteocytes close to bone marrow

Provides strength with minimal weight

Trabeculae develop along bone’s lines of stress
Spongy Bone Structure in Relation to
Mechanical Stress

Figure
7.5
 Bone Marrow
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Bone marrow—soft tissue

occupying marrow cavities of long
bones and small spaces of spongy
bone
Red marrow (myeloid tissue)
Contains hemopoietic tissue—
produces blood cells
In nearly every bone in a child
In adults, found in skull, vertebrae,
ribs, sternum, part of pelvic girdle,
and proximal heads of humerus and
femur
Yellow marrow found in adults
Fatty marrow that does not produce
blood
Can transform back to red marrow in
Figure the event of chronic anemia
7.6
 Bone Development

Expected Learning Outcomes

Describe two mechanisms of bone
formation.
Explain how mature bone continues to
grow and remodel itself.
 Bone Development

Ossification or osteogenesis—the
formation of bone

In the human fetus and infant, bone

develops by two methods
Intramembranous ossification
Endochondral ossification
Intramembranous Ossification

Figure 7.7

Produces flat bones of skull and clavicle in

fetus
Intramembranous Ossification

Figure
7.8
Note the periosteum and osteoblasts
 Endochondral Ossification
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Artic
Spongy
ular
bone
carti
lage Epiphy
seal
line
Perichon
drium
Hyal Secondar
Epiphy Periost
ine y eum
marrow seal
carti
1 Early cartilage cavity plate
lage Epiph Nutr
model Second ient Marrow
ysis
ary Metap fora cavity
ossific hysis men
Compact
ation
Bl bone
Enlargin center
g oo
d Diaph
chondro
Bony ve
Pri ysis
cytes
collar
Primar ss
mar
y el
y
ossific mar Metap
ation row Second hysis
Periost Carti
center cavi ary
eum lage
ty ossific
Formation of Vascular ation
Bone at birth, Bone of Adult bone
2 3 4 5 6
primary invasion, with center child, with with a
ossification formation of enlarged epiphyseal single
center, primary primary plate at marrow
bony collar, marrow cavity, marrow cavity distal end cavity and
and and and closed
periosteum appearance of appearance of epiphyseal
secondary secondary Figure plate
ossification marrow
center cavity in one 7.9
 Endochondral Ossification

During infancy and childhood, the

epiphyses fill with spongy bone

Cartilage limited to the articular cartilage

covering each joint surface, and to the
epiphyseal plate
A thin wall of cartilage separating the primary
and secondary marrow cavities
Epiphyseal plate persists through childhood and
adolescence
Serves as a growth zone for bone elongation
 Endochondral Ossification

By late teens to early 20s, all remaining

cartilage in the epiphyseal plate is
generally consumed
Gap between epiphyses and diaphysis closes
Primary and secondary marrow cavities unite into
a single cavity
Bone can no longer grow in length
The Fetal Skeleton at 12 Weeks

Figure
Bone Growth and Remodeling
Ossification continues throughout life
with the growth and remodeling of bones

Bones grow in two directions

Length
Width
X-Ray of Child’s Hand Epiphyseal Plates

Figure
7.11
 Bone Elongation
Epiphyseal plate—cartilage transitions to bone
Functions as growth zone where bone elongates
Has typical hyaline cartilage in the middle with
transition zones on each side where cartilage is
replaced by bone
Metaphysis is zone of transition facing the marrow
cavity
This is interstitial growth—growth from within
Bone elongation is a result of cartilage growth within
the epiphyseal plate
Epiphyses close when cartilage is gone—epiphyseal
line of spongy bone marks site of former epiphyseal
plate
Lengthwise growth is finished
Occurs at different ages in different bones
Zones of the Metaphysis

Figure
7.12
 Dwarfism

Achondroplastic
dwarfism
Long bones stop growing
in childhood
Normal torso, short limbs
Failure of cartilage growth
in metaphysis
Spontaneous mutation
produces mutant
dominant allele

Pituitary dwarfism
Lack of growth hormone
Normal proportions with
short stature
Figure
7.13
Bone Widening and Thickening

Appositional growth—occurs at bone

surface
Continual growth in diameter and thickness
Intramembranous ossification
Osteoblasts of inner periosteum deposit osteoid
tissue
Become trapped as tissue calcifies
Lay down matrix in layers parallel to surface
Forms circumferential lamellae
Osteoclasts of endosteum enlarge marrow
cavity
 Bone Remodeling

Bone remodeling (absorption and

deposition) occurs throughout life—10% of
skeleton per year
Repairs microfractures, releases minerals into
blood, reshapes bones in response to use and
disuse
Wolff’s law of bone: architecture of bone
determined by mechanical stresses placed on it
Remodeling is a collaborative and precise action of
osteoblasts and osteoclasts
Bony processes grow larger in response to
mechanical stress
Physiology of Osseous Tissue
Expected Learning Outcome
Describe the processes by which minerals are
added to and removed from bone tissue.
Describe the role of the bones in regulating
blood calcium and phosphate levels.
Name several hormones that regulate bone
physiology and describe their effects.
Physiology of Osseous Tissue

A mature bone remains a metabolically

active organ
Involved in its own maintenance of growth and
remodeling
Exerts a profound influence over the rest of the
body by exchanging minerals with tissue fluid
Disturbance of calcium homeostasis in skeleton
disrupts function of other organ systems
Especially nervous and muscular
Mineral Deposition and Resorption
Mineral deposition (mineralization)—
process in which calcium, phosphate, and
other ions are taken from blood and deposited
in bone
Osteoblasts produce collagen fibers that spiral
the length of the osteon
Fibers become encrusted with minerals
Hydroxyapatite crystals form at solubility product
—critical level of calcium times phosphate
concentration
First few crystals act as seed crystals that attract
more calcium and phosphate from solution
Abnormal calcification (ectopic ossification)—
formation of a calculus (calcified mass) in an
otherwise soft organ such as a lung, brain, eye,
muscle, tendon, or artery (arteriosclerosis)
 Mineral Deposition and
Resorption

Mineral resorption—process of dissolving bone

and releasing minerals into blood
Performed by osteoclasts at ruffled border
Hydrogen pumps in membranes secrete hydrogen
into space between osteoclast and bone surface
Chloride ions follow by electrical attraction
Hydrochloric acid (pH 4) dissolves bone minerals
Acid phosphatase enzyme digests collagen
Orthodontic appliances (braces) reposition
teeth through resorption and deposit
Tooth moves because osteoclasts dissolve bone ahead
of tooth; osteoblasts deposit bone behind the tooth
 Calcium Homeostasis
Calcium and phosphate are used for
much more than bone structure
Phosphate is a component of DNA,
RNA, ATP, phospholipids, and pH
buffers
Calcium needed in neuron
communication, muscle contraction,
blood clotting, and exocytosis
Minerals are deposited in the skeleton
and withdrawn when they are needed
for other purposes
 Calcium Homeostasis
Total of about 1,100 g of calcium in
adult body with 99% of it in bones
Most exists as part of hydroxyapatite, but a little is
in a form that is easily exchanged with the blood
About 18% of skeletal calcium is exchanged with
blood each year

Normal calcium concentration in blood

plasma is 9.2 to 10.4 mg/dL
45% as Ca2+ that can diffuse across capillary walls
and affect other tissues
Rest in reserve, bound to plasma proteins
 Calcium Homeostasis

Hypocalcemia—deficient calcium in blood

Changes membrane potentials and causes overly
excitable nervous system and tetany (muscle
spasms)
Laryngospasm can cause suffocation
Caused by vitamin D deficiency, diarrhea, thyroid
tumors, underactive parathyroid glands
Pregnancy and lactation increase risk of
hypocalcemia
Hypercalcemia—excessive calcium levels
Makes ion channels less responsive and thus nerve
and muscle are less excitable
Can cause emotional disturbance, muscle weakness, sluggish
reflexes, cardiac arrest
Hypercalcemia rarely occurs
 Calcitriol

Calcitriol—most active form of vitamin D

Produced by actions of skin, liver, and kidneys
Epidermal keratinocytes use UV radiation to convert
7-dehydrocholesterol to previtamin D3; warm
sun on skin converts this to vitamin D3
Liver adds hydroxyl group converting that to calcidiol
Kidney adds hydroxyl group converting that to
calcitriol
 Calcitriol

Calcitriol is a hormone that raises blood

calcium level
Mainly, it increases calcium absorption by small
intestine
It also increases calcium resorption from the
skeleton
Stimulates osteoblasts to release RANKL, a chemical
that stimulates production of more osteoclasts
It weakly promotes kidney reabsorption of
calcium ions, so less lost in urine
Calcitriol Synthesis and Action
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

7-
dehydrochole
Ultrasterol
viole
H t
O light

Vitamin
D3
(cholecalc
iferol)
C
H
2

H
Bone
O
reso
Cal rptio
cidi nRed
ol uce
O d
C H excr
H etio
2
Cal n
citri of
H O ol Absor
O Ca 2+
H ption
C of
H Ca2+
2
and
H phos
O phate
O
H

Figure
7.14
 Calcitriol
Calcitriol is also necessary for bone
deposition—helping provide adequate
calcium and phosphate
Inadequate calcitriol results in abnormal
softness of bones in children (rickets) and in
adults (osteomalacia)
 Calcium Homeostasis
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Calcium Intake and B B

Excretion l o
o n
o e
Dietary d
requirement
1,000
mg/day
Depositi
Absorpt on by
Digestive ion by osteobla
tract digestiv sts
Calcito
eCal
tract Ca2+ nin
citri Hydroxya
(9.2–10.4 (weak
ol patite
mg/dL) effect)
Ca10(PO4)
6(OH)2
Kid
ney Calcium
s Filtra carbonate
Resorpt CaCO3
tion ion by
by
kidne Cal
osteocl
ys citri
asts
Reabso ol
rption PTH
by
Calcitri
kidneys
ol
(weak
effect)
PTH

Fecal
loss
Urinar
y loss Figure
350 650
mg/d
ay
mg/da
y
7.15

Calcitriol, calcitonin, and PTH maintain

normal blood calcium concentration
 Calcitonin
Calcitonin—secreted by C cells (clear cells)
of thyroid gland when blood calcium levels
rise too high
Lowers blood calcium concentration in
two ways:
Inhibits osteoclasts thereby reducing bone
resorption
Stimulates osteoblasts to deposit calcium into bone
Important in children, weak effect in
adults
Osteoclasts more active in children due to faster
remodeling
May inhibit bone loss in pregnant and
lactating women
 Parathyroid Hormone
Parathyroid hormone (PTH)—secreted by
parathyroid glands on posterior surface of
thyroid
PTH released when calcium levels low in
blood
PTH raises calcium blood level by four
mechanisms
Stimulates osteoblasts to secrete RANKL, thereby
increasing osteoclast population and bone resorption
Promotes calcium reabsorption by kidneys, so less lost
in urine
Promotes the final step of calcitriol synthesis in the
kidneys, enhancing calcium-raising effect of calcitriol
Inhibits collagen synthesis by osteoblasts, inhibiting
bone deposition
 Calcium Homeostasis
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Blood Blood
Ca2+ Ca2+
excess return
s to
normal

Calcit
onin
secret
ion

Reduc
Less
ed
bone
osteoc
resorp
last
tion
activit
y

Increa
More
sed
bone
osteob
deposi
last
tion
(a) Correction for activit Figure
y
Calcium Homeostasis
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Blood Blood
Ca2+ Ca2+
deficie return
ncy s to
norma
Parath l
yroid
hormo
ne
secreti Increa
More
on sed
bone
osteo
resorp
clast
tion
activit
y
Reduc
Less
ed
bone
osteo
deposi
blast
tion
activit
y
More Preventio
urinary n of
phosph hydroxya
ate patite
excretio formation
n
Less Conserv
urinary ation
calcium of
(b) Correction for
excretio
n
Figure calcium
 Phosphate Homeostasis
Average adult has 500 to 800 g
phosphorus with 85% to 90% of it in the
bones
Normal plasma concentration is 3.5 to 4.0
mg/dL
Occurs in two main forms
HPO42− and H2PO4− (monohydrogen and
dihydrogen phosphate ions)
Phosphate levels are not regulated as
tightly as calcium levels
Calcitriol raises phosphate levels by
promoting its absorption by small intestine
PTH lowers blood phosphate levels by
promoting its urinary excretion
Other Factors Affecting Bone

At least 20 or more hormones,

vitamins, and growth factors affect
osseous tissue

Bone growth especially rapid in

puberty and adolescence
Surges of growth hormone, estrogen, and
testosterone occur and promote ossification
These hormones stimulate multiplication of
osteogenic cells, matrix deposition by
osteoblasts, and chondrocyte multiplication and
hypertrophy in metaphyses
Other Factors Affecting Bone
(Continued)
Girls grow faster than boys and reach full
height earlier
Estrogen has stronger effect than testosterone
on bone growth
Males grow for a longer time and also taller

Anabolic steroids cause growth to stop

Epiphyseal plate “closes” prematurely
Results in abnormally short adult stature
 Bone Disorders
Expected Learning Outcomes
Name and describe several bone diseases.
Name and describe the types of fractures.
Explain how a fracture is repaired.
Discuss some clinical treatments for fractures
and other skeletal disorders.
 Bone Disorders
Orthopedics—branch of medicine dealing
with prevention and correction of injuries
and disorders of bones, joints, and
muscles
Name implies its origin as field treating
skeletal deformities in children
Includes the design of artificial joints
and limbs and the treatment of
athletic injuries
 Fractures and Their Repair
Stress fracture—break caused by abnormal
trauma to a bone (example: in a fall)
Pathological fracture—break in a bone
weakened by disease (such as bone cancer or
osteoporosis)
Usually caused by a stress that would not break a
healthy bone
Fractures classified by structural characteristics
Direction of fracture line
Break in the skin
Multiple pieces
Example: comminuted—three or more pieces
Types of Bone Fractures

Figure
7.17
Healing of Fractures

Figure
7.18
 The Treatment of Fractures

Closed reduction—procedure in which bone

fragments are manipulated into their normal
positions without surgery

Open reduction—involves surgical exposure

of the bone and the use of plates, screws, or
pins to realign the fragments

Cast—normally used to stabilize and

immobilize healing bone
 The Treatment of Fractures

Fractures of the femur in children often treated

with traction
Aligns bone fragments by overriding force of the
strong thigh muscles

Hip fractures in older adults are usually

pinned and early walking is encouraged
Fractures taking more than 2 months to heal may
be treated with electrical stimulation which
suppresses effects of parathyroid hormone
Open Reduction of an Ankle Fracture

Figure
7.19
 Other Bone Disorders
Osteoporosis—the most common bone
disease
Severe loss of bone density

Bones lose mass and become brittle due

to loss of organic matrix and minerals
Affects spongy bone the most since it is the most
metabolically active
Subject to pathological fractures of hip, wrist, and
vertebral column
Kyphosis (widow’s hump)—deformity of spine
due to vertebral bone loss
Complications of loss of mobility are pneumonia
and thrombosis
 Osteoporosis
Estrogen maintains bone density in both
sexes; inhibits resorption by osteoclasts

Postmenopausal white women at greatest

risk
Ovaries cease to secrete estrogen
White women begin to lose bone mass as early as age
35
By age 70, average loss is 30% of bone mass
Risk factors: race, age, gender, smoking, diabetes
mellitus, diets poor which are poor in: calcium, protein,
vitamins C and D

Osteoporosis also seen in young female

athletes with low body fat causing them to
stop ovulating and decrease estrogen
secretion
 Osteoporosis
(Continued)
Treatments
Estrogen replacement therapy (ERT) slows
bone resorption, but increases risk of breast
cancer, stroke, and heart disease
Drugs Fosamax, Actonel destroy osteoclasts
PTH slows bone loss if given as daily injection
Forteo (PTH derivative) increases density by 10% in
1 year
May promote bone cancer so use is limited to 2 years
Best treatment is prevention: exercise and a
good bone-building diet between ages 25 and 40
Osteoporosis

Figure 7.20
a,b