More Ch. 6
6.5 – 6.10
Bone Growth, Composition
and Conditions
Ossification
• Skeleton begins to form in embryo at 6 week
• During all future development bone undergoes
increases in size and ossification
o Ossification = bone formation
o Calcification = deposition of calcium
o Endochondral ossification = bone replaces cartilage that was already
presesnt
o Intramembranous ossification = bone develops directly from connective
tissue
• Bone growth continues through adolescence, and
on average until about age 25
• Toes “done” by age 11; pelvis and wrists may still be
growing at 25. Lots of growth happens in relation to
puberty hormones
Endochondryal
Ossification
• Chondros = cartilage
• Endo = inside
• Most bones start as hyaline cartilage and are
“models of adult bone” size and shape
• Cartilage gradually replaced by bone
• Time line: “This is an essay; timeline and pictures that follow”
o
o
o
o
o
o
o
o
6 weeks proximal end of limb bone present but as hyaline cartilage
New cartilage on outer surface
Cells at center enlarge, blood vessels grow
Primary ossification starts and spread toward ends
Increases in length and in diameter
Centers of epiphyses calcify and become spongy bone
Cap of cartilage remains at articulation
Region of cartilage between epiphysis and diaphysis = lengthening bone
Figure 6-10 Endochondral Ossification (Step 1-7)
THIS IS AN
ESSAY
QUESTION
As the cartilage
enlarges,
chondrocytes near
the center of the
shaft increase
greatly in size. The
matrix is reduced to
a series of small
struts that soon
begin to calcify. The
enlarged
chondrocytes then
die and disintegrate,
leaving cavities
within the cartilage.
Blood vessels grow
around the edges of
the cartilage, and
the cells of the
perichondrium
convert to
osteoblasts. The
shaft of the
cartilage then
becomes
ensheathed in a
superficial layer of
bone.
Enlarging
chondrocytes within
calcifying matrix
Blood vessels
penetrate the cartilage
and invade the central
region. Fibroblasts
migrating with the
blood vessels
differentiate into
osteoblasts and begin
producing spongy
bone at a primary
ossification center.
Bone formation then
spreads along the
shaft toward both
ends.
Remodeling occurs
as growth continues,
creating a medullary
cavity. The osseous
tissue of the shaft
becomes thicker,
and the cartilage
near each epiphysis
is replaced by shafts
of bone. Further
growth involves
increases in length
and diameter.
Epiphysis
Medullary
cavity
Blood
vessel
Diaphysis
Medullary
cavity
Primary
ossification
center
Superficial
bone
Spongy
bone
Metaphysis
Bone
formation
Hyaline cartilage
Capillaries and
osteoblasts migrate
into the epiphyses,
creating secondary
ossification centers.
Hyaline cartilage
Soon the epiphyses are
filled with spongy bone.
An articular cartilage
remains exposed to the
joint cavity; over time it
will be reduced to a thin
superficial layer. At each
metaphysis, an epiphyseal
cartilage separates the
epiphysis from the
diaphysis.
Epiphysis
Articular cartilage
Metaphysis
Spongy
bone
This light micrograph shows the ossifying
surface of an epiphyseal cartilage. The pink
material is osteoid, deposited by osteoblasts in
the medullary cavity. On the shaft side of the
epiphyseal cartilage, osteoblasts are
continuously invading the cartilage and replacing
it with bone. On the epiphyseal side, new cartilage
is continuously being added. The osteoblasts are
therefore moving toward the epiphysis, which is
being pushed away by the expansion of the
epiphyseal cartilage. The osteoblasts won’t catch
up to the epiphysis, as long as both the
osteoblasts and the epiphysis “run away” from
the primary ossification center at the same rate.
Meanwhile, the bone grows longer and longer.
Epiphyseal
cartilage matrix
Cartilage cells undergoing
division and secreting
additional cartilage matrix
Periosteum
Compact
bone
Epiphyseal
cartilage
Diaphysis
Secondary
ossification
center
LM  250
Medullary cavity Osteoblasts Osteoid
Figure 6-10 Endochondral Ossification (Step 1-4)
As the cartilage
enlarges,
chondrocytes near
the center of the
shaft increase
greatly in size. The
matrix is reduced to
a series of small
struts that soon
begin to calcify. The
enlarged
chondrocytes then
die and disintegrate,
leaving cavities
within the cartilage.
Blood vessels grow
around the edges of
the cartilage, and
the cells of the
perichondrium
convert to
osteoblasts. The
shaft of the
cartilage then
becomes
ensheathed in a
superficial layer of
bone.
Enlarging
chondrocytes within
calcifying matrix
Blood vessels
penetrate the cartilage
and invade the central
region. Fibroblasts
migrating with the
blood vessels
differentiate into
osteoblasts and begin
producing spongy
bone at a primary
ossification center.
Bone formation then
spreads along the
shaft toward both
ends.
Epiphysis
Medullary
cavity
Blood
vessel
Diaphysis
Primary
ossification
center
Bone
formation
Medullary
cavity
Superficial
bone
Spongy
bone
Hyaline cartilage
Remodeling occurs
as growth continues,
creating a medullary
cavity. The osseous
tissue of the shaft
becomes thicker,
and the cartilage
near each epiphysis
is replaced by shafts
of bone. Further
growth involves
increases in length
and diameter.
Metaphysis
Figure 6-10 Endochondral Ossification (Steps 5-7)
Capillaries and
osteoblasts migrate
into the epiphyses,
creating secondary
ossification centers.
Hyaline cartilage
Soon the epiphyses are
filled with spongy bone.
An articular cartilage
remains exposed to the
joint cavity; over time it
will be reduced to a thin
superficial layer. At each
metaphysis, an epiphyseal
cartilage separates the
epiphysis from the
diaphysis.
Epiphysis
This light micrograph shows the ossifying
surface of an epiphyseal cartilage. The pink
material is osteoid, deposited by osteoblasts in
the medullary cavity. On the shaft side of the
epiphyseal cartilage, osteoblasts are
continuously invading the cartilage and replacing
it with bone. On the epiphyseal side, new cartilage
is continuously being added. The osteoblasts are
therefore moving toward the epiphysis, which is
being pushed away by the expansion of the
epiphyseal cartilage. The osteoblasts won’t catch
up to the epiphysis, as long as both the
osteoblasts and the epiphysis “run away” from
the primary ossification center at the same rate.
Meanwhile, the bone grows longer and longer.
Articular cartilage
Metaphysis
Spongy
bone
Epiphyseal
cartilage matrix
Cartilage cells undergoing
division and secreting
additional cartilage matrix
Periosteum
Compact
bone
Epiphyseal
cartilage
Diaphysis
Secondary
ossification
center
LM  250
Medullary cavity
Osteoblasts
Osteoid
APPOSITIONAL GROWTH =
Superficial layers of bone forms early in endochondral ossification
New growth in the bones diameter results in layers –
New lamella added in concentric rings around outside while inner layers
are recycled
An x-ray of growing epiphyseal
cartilages (arrows)
Epiphyseal lines in an
adult (arrows)
Intramembranous
Ossification
• Osteoblasts differentiate
o
o
o
o
o
o
o
Fibrous connective tissue ( mesenchymal cells)
Matrix is created
Crystallization of calcium salts
Very active process requiring lots of nutrients
Osteoblasts ossification  spicules form
Initially only spongy bone
Remodeling can lead to compact bone
• Creates dermal bones
o Flat bones of skull, mandible (lower jaw), and clavicle (collar bone)
Blood and nerve
supply to bones
• Bone maintenance and grow require blood supply
• Osseous tissue is highly vascular
o Nutrient artery and vein: supply diaphysis, usually only one of each ( femur
has more)
o Enter through foramina – branch into smaller canals
o Metaphyseal vessels – supply blood to cartilage that is or will be replaced
by bone
o Periosteal vessels – blood to periosteum and superficial osteons – branch
during ossification
o All are very interconnected
• Lymph – connect blood and lymph through osteons
• Nerves – travel along nutrient artery ( injuries to
bones are very painful)
Remodeling
• Bone matrix constantly being recycled and
renewed
• Used for both maintenance and changes to bone
shape and structure
• Youth – recycle about 1/5 of calcium salts per year;
more likely in areas of spongy bone
• Heavy metals are dangerous because they can be
incorporated into bone – stay in circulatory system
for many years. (Chernobyl Nuclear reactor leak;
1986 Ukraine, only other level 7 leak is Fukushuma
Daiichi in 2011)
Impact of Exercise
on bones
• “stresses” on mineral crystals cause bone growth
• Increases in muscle mass increase both weight and
tension on bones = growth
• Ridges and bumps on bone relate to pull of
tendons, diameter of bone relates to mass –
• non-athletes have more fragile bones (osteoporosis
and arthritis)
• A broken leg with no stress, can lose 1/3 mass while
using crutches
• ? Bedridden and paralyzed
Impact of Hormones
on bones
•
•
•
•
•
•
Calcitrol:
o
o
made by kidneys
increases absorption of Ca and PO4 in digestive tract
o
o
Made by pituitary
Stimulates osteoblast and synthesis of matrix
o
o
Thyroid
Also stimulates osteoblasts and synthesis of matrix
o
o
o
Ovaries and testes
Stimulates osteoblasts
Estrogen closes epiphysis earlier than androgens
o
o
o
Parathyroid glands
Stimulates osteoclasts and osteoblasts
Increases Ca level in body fluids
o
o
o
o
Thyroid gland
Inhibits osteoclasts
Reduces Ca in body fluids
Triggers kidneys to lose calcium
Growth hormone
Thyroxine
Estrogen/ androgens
Parathyroid hormone
Calcitonin
NOT a
memorize slide
Impact of Nutrition
on bones
• Dietary sources of calcium and phosphate are
required for healthy bone growth and maintenance
• Also required are: magnesium, fluoride, iron and
manganese
• Vitamin C is needed for enzymatic reaction that
makes cartilage
• Vitamin D is required for calcitrol to cause intestinal
absorption of Ca and PO4
• Vitamins A, K and B12 are also needed for normal
bone growth
Nutrition and Calcium
• Bones are a mineral reservoir
o 1-2 Kg of calcium ( 2.2 – 4.4 lbs) in body
o 99% is in the bones
• Calcium levels are important for many functions:
o Permeability of plasma membranes
o Firing of nerve impulses
o Contraction of muscle fibers
o Widely varying ion concentrations can result in seizures or death
o “electrolytes”
Figure 6-16a Factors That Alter the Concentration of Calcium Ions in Body Fluids
Factors That Increase Blood Calcium Levels
These responses are
triggered when plasma
calcium ion concentrations
fall below 8.5 mg/dL.
Low Calcium Ion Levels in Plasma
(below 8.5 mg/dL)
Parathyroid Gland Response
Low calcium plasma levels cause
the parathyroid glands to secrete
parathyroid hormone (PTH).
PTH
Bone Response
Osteoclasts stimulated to
release stored calcium ions
from bone
Osteoclast
Intestinal Response
Kidney Response
Rate of
intestinal
absorption
increases
Kidneys retain
calcium ions
more
Bone
Calcium released
calcitriol
Calcium absorbed quickly
↑Ca2+
levels in
bloodstream
Calcium conserved
Decreased calcium
loss in urine
Figure 6-16b Factors That Alter the Concentration of Calcium Ions in Body Fluids
Factors That Decrease Blood Calcium Levels
These responses are
triggered when plasma
calcium ion concentrations
rise above 11 mg/dL.
HIgh Calcium Ion Levels in Plasma
(above 11 mg/dL)
Thyroid Gland Response
Parafollicular cells (C cells) in the
thryoid gland secrete calcitonin.
Calcitonin
Bone Response
Osteoclasts inhibited while
osteoblasts continue to lock
calcium ions in bone matrix
Intestinal Response
Kidney Response
Rate of intestinal
absorption
decreases
Kidneys allow
calcium loss
less
Bone
calcitriol
Calcium absorbed slowly
Calcium excreted
Calcium stored
↓Ca2+
levels in
bloodstream
Increased calcium
loss in urine
Fractures
• Crack or break in bone
• Often from stress in unusual direction
• Need blood supply and portions of endosteum and
periosteum in order to survive
• Repair:
o
o
o
o
Spongy bone forms
External callus of cartilage stabilizes bone
Cartilage is replaced by bone
Remodeling removes dead bone or extra layers
• Fracture types:
o Transverse, displaced, compression, spiral, epiphyseal, communicated
(shatter), greenstick
Figure 6-17 Types of Fractures and Steps in Repair
Epiphyseal fracture
Displaced fracture
Transverse fracture
Compression
fracture
TYPES OF
FRACTURES
Fractures are named according
to their external appearance,
their location, and the nature of
the crack or break in the bone.
Important types of fractures are
illustrated here by
representative x-rays. The
broadest general categories are
closed fractures and open
fractures. Closed, or simple,
fractures are completely
internal. They can be seen only
on x-rays, because they do not
involve a break in the skin.
Open, or compound, fractures
project through the skin. These
fractures, which are obvious on
inspection, are more dangerous
than closed fractures, due to the
possibility of infection or
uncontrolled bleeding. Many
fractures fall into more than one
category, because the terms
overlap.
Transverse fractures,
such as this fracture of
the ulna, break a bone
shaft across its long
axis.
Displaced fractures
produce new and
abnormal bone
arrangements;
nondisplaced fractures
retain the normal
alignment of the bones
or fragments.
REPAIR OF A
Compression fractures
occur in vertebrae
subjected to extreme
stresses, such as
those produced by the
forces that arise when
you land on your seat
in a fall.
Spiral fractures,
such as this fracture
of the tibia, are
produced by twisting
stresses that spread
along the length of
the bone.
FRACTURE
Epiphyseal fractures, such as this
fracture of the femur, tend to
occur where the bone matrix is
undergoing calcification and
chondrocytes are dying. A clean
transverse fracture along this line
generally heals well. Unless
carefully treated, fractures
between the epiphysis and the
epiphyseal cartilage can permanently stop growth at this site.
Comminuted fractures,
such as this fracture of
the femur, shatter the
affected area into a
multitude of bony
fragments.
In a greenstick fracture,
such as this fracture of
the radius, only one side
of the shaft is broken, and
the other is bent. This
type of fracture generally
occurs in children, whose
Long bones have yet to
ossify fully.
Fracture
hematoma
External
callus
Dead
bone
Bone
fragments
Immediately after the
fracture, extensive
bleeding occurs. Over a
period of several hours, a
large blood clot, or fracture
hematoma, develops.
Spongy bone of
external callus
Periosteum
An internal callus forms as a
network of spongy bone
unites the inner edges, and an
external callus of cartilage and bone
stabilizes the outer edges.
Internal
callus
External
callus
The cartilage of the external
callus has been replaced by
bone, and struts of spongy bone now
united the broken ends. Fragments of
dead bone and the areas of bone
closest to the break have been
removed and replaced.
A swelling initially
marks the location of
the fracture. Over time, this
region will be remodeled,
and little evidence of the
fracture will remain.
A Colles fracture, a
break in the distal
portion of the radius,
is typically the result
of reaching out to
cushion a fall.
A Pott’s fracture
occurs at the ankle
and affects both
bones of the leg.
Diseases and Disorders
• Osteopenia = inadequate ossification
o Aging ; begins between 30 and 40
o Lose 3% per decade
o Vertebrae and jaw lose mass faster - spinal issues and loss of teeth
• Osteoporosis – enough bone is lost to compromise
normal function
o Also related to decreasing estrogen and androgens
o More of an issue in women because of menopause
• Cancers