PATHOLOGY OF THE
MSc. PTH - Clinical Pathology (UNZA), B.Sc. (UNZA)
Sunday, April 26, 2015 1
Congenital diseases of bone
Acquired diseases of bone development
Metabolic bone disease
Bone tumorsSunday, April 26, 2015 2
CONGENITAL DISEASES OF BONE
1. Osteogenesis Imperfecta
Osteogenesis imperfecta (OI) (brittle bone
disease) is a genetic disorder characterized by
hard and easily broken bones often from
little or no apparent cause.
It is due to a genetic defect in collagen type I
affecting the body’s ability to make strong
Sunday, April 26, 2015 3
Most common and mildest type of OI.
Bones fracture easily.
Normal or near-normal stature.
Loose joints and muscle weakness.
Sclera usually have a blue, purple, or gray tint.
Hearing loss possible, often beginning in early
20s or 30s.Sunday, April 26, 2015 4
Most severe form.
Numerous fractures and
severe bone deformity.
Small stature with
Sunday, April 26, 2015 5
Barrel-shaped rib cage.
Bone deformity, often
Brittle teeth possible.
Hearing loss possible.
Sunday, April 26, 2015 6
Achondroplasia means "without cartilage
It is a genetic condition characterized by a
short stature caused by a defect in
converting cartilage into bones (ossification)
particularly in the long bones.
It is the most common cause of dwarfism.
Sunday, April 26, 2015 7
It is caused by mutations in the fibroblast
growth factor receptor 3 (FGFR3) gene.
This gene provides instructions for making a
protein called FGFR3 protein which is involved
in the development and maintenance of bones.
This genetic change causes the receptor to be
very active, which leads to the disturbances in
the ossification of bones.
Achondroplasia is inherited in an autosomal
dominant pattern.Sunday, April 26, 2015 8
Clients have short stature
The average height of an adult
male is 131 cm adult females is 124
Have an average-size trunk,
Short arms and legs with particularly
short upper arms and thighs,
Limited range of motion at the
A big head (macrocephaly) with a
prominent forehead.Sunday, April 26, 2015 9
ACQUIRED DISEASES OF BONE DEVELOPMENT
A fracture is a broken bone. A bone may be
completely fractured or partially fractured in any
number of ways.
The most common causes of fractures are:
Trauma. A fall, a motor vehicle accident, or
trauma during a football game can all result in
Sunday, April 26, 2015 10
Osteoporosis. This disorder weakens bones
and makes them more likely to break
Overuse. Repetitive motion can tire muscles
and place more force on bone.
This can result in stress fractures. Stress
fractures are more common in athletes.
Sunday, April 26, 2015 11
Common types of fractures
Stable fracture. The broken
ends of the bone line up and
are barely out of place.
Open or compound fracture.
The skin is pierced by the bone
that breaks the skin at the time
of the fracture.
The bone may or may not be
visible in the wound.
Sunday, April 26, 2015 12
Common types …………..
This type of fracture has
a horizontal fracture line.
Oblique fracture. This
type of fracture has an
In this type of fracture,
the bone shatters into
three or more pieces.Sunday, April 26, 2015 13
Pain on the affected area
Un able to move the injured
Other common symptoms
Swelling and tenderness
around the injury area
Deformity — a limb may look
"out of place" or a part of the
bone may puncture through
the skinSunday, April 26, 2015 14
Osteonecrosis (ON) is a focal infarct of bone
that may be caused by specific etiologic factors
or may be idiopathic.
Causes/ Risk factors
No one is sure what causes the disease.
Risk factors include;
Long-term steroid treatment
Having diseases such as arthritis and cancerSunday, April 26, 2015 15
Mechanisms of non-traumatic ON include
embolization by blood clots or lipid droplets.
This leads to the death of osteocytes and bone
After the vascular insult, the repair processes
attempt to remove necrotic bone and marrow
and replace them with viable tissue.
If the infarct is small, this process may succeed.
Sunday, April 26, 2015 16
However, in some patients,
the process is not successful
and the infarct gradually
The overlying articular
surface becomes flattened
and irregular, causing
increased pain and
eventually leading to
osteoarthritis.Sunday, April 26, 2015 17
Symptoms and Signs
Patients may remain asymptomatic for weeks
to months after the vascular insult.
Pain then develops gradually with progressive
collapse of the joint
Pain increases and is worsened by motion and
weight bearing and is relieved by rest.Sunday, April 26, 2015 18
Osteomyelitis is an infection in a bone.
Most cases of osteomyelitis are caused by
Staphylococcus aureus (Pyogenic
Osteomyelitis) and Mycobacterium
tuberculosis (Tuberculous Osteomyelitis)
Micro – organisms can enter a bone in 3 ways;
Via the bloodstream. infection in other parts
of the body — for example pneumonia or a
urinary tract infection — can travel through
bloodstream to a bone.Sunday, April 26, 2015 19
From a nearby infection. Severe puncture
wounds can carry germs deep inside the body.
If such an injury becomes infected, the germs
can spread into a nearby bone.
Direct contamination. This may occur in cases
Direct contamination can also occur during
surgeries to replace joints or repair fractures.Sunday, April 26, 2015 20
Recent injury or orthopedic surgery
Poorly controlled diabetes
Peripheral arterial disease, often related to
Sickle cell disease
Sunday, April 26, 2015 21
Osteomyelitis tends to occlude local blood
vessels, which causes bone necrosis and
spread of infection to the bones.
Infection may inflate through the bone cortex
and spread under the periosteum, with
formation of subcutaneous abscesses that
may drain spontaneously through the skin.
Sunday, April 26, 2015 22
Signs and symptoms
Fever or chills
Irritability or lethargy in young
Localized bone pain
Swelling, warmth and redness
over the area of the infection
Sometimes osteomyelitis causes
no signs and symptoms or has
signs and symptoms that are
difficult to distinguish from
other problems.Sunday, April 26, 2015 23
Osteonecrosis - Bone death
Skin cancer. If osteomyelitis has resulted in an
open sore that is draining pus, the surrounding
skin is at higher risk of developing squamous
Sunday, April 26, 2015 24
METABOLIC BONE DISEASE
Osteoporosis AKA “porous bone” is a
disease characterized by increased sponginess
of the skeleton resulting from reduced bone
Sunday, April 26, 2015 25
Osteoporosis can be primary or secondary
disorder due to some other factor.
Primary disorder can further be classified as;
Type 1 or postmenopausal osteoporosis is
associated with decreased levels of estrogen
and has a greater effect on trabecular than
Type 2 or senile osteoporosis is a
consequence of aging and is often augmented
by inadequate calcium and vitamin D intake.Sunday, April 26, 2015 26
Bone is continually being formed and resorbed.
Osteoblasts and osteoclasts (cells that resorb
bone) are regulated by parathyroid hormone
(PTH), calcitonin, estrogen, vitamin D,
various cytokines, and other local factors such
Peak bone mass in men and women occurs by
the mid 20s.
Normally, bone formation and resorption is
closely balanced.Sunday, April 26, 2015 27
Blacks reach higher bone mass than whites
Men have higher bone mass than women.
After achieving peak for about 10 years, bone
loss occurs at a rate of about 0.3 to 0.5%/yr.
In menopause, bone loss is accelerated to about
3 to 5%/yr for about 5 to 7 yr and then the
rate of loss slows.
Osteoporosis occurs when bone loss exceeds
bone formation, resulting in a low bone mass.Sunday, April 26, 2015 28
Sunday, April 26, 2015 29
Race (Caucasians > African Americans)
Sex (F > M)
Slender body build
Calcium nutritional state - insufficient dietary
Sunday, April 26, 2015 30
Signs and Symptoms
Patients with osteoporosis
are asymptomatic unless a
fracture has occurred.
The trabecular plates
thinned, and lose their
to progressive micro
fractures.Sunday, April 26, 2015 31
2. Osteomalacia and Rickets
Osteomalacia refers to a softening of bones,
often caused by vitamin D deficiency in
Rickets is the softening and weakening of
bones in children, usually because of an
extreme and prolonged vitamin D deficiency.
Sunday, April 26, 2015 32
Vitamin D promotes the absorption of
calcium and phosphorus from the
Deficiency of vitamin D makes it difficult to
maintain proper calcium and phosphorus
levels in bones, which can cause soft bones .
Soft bones are more likely to bow and
fracture than are harder and healthy bones.Sunday, April 26, 2015 33
Sign and symptoms
The most common signs
and symptoms are bowled
Sunday, April 26, 2015 34
3. Paget’s disease of the bone
Paget's disease is a localized disorder of bone
transformation that typically begins with
excessive bone resorption followed by an
increase in bone formation.
This results in deformity of the affected bones.
The disease occurs worldwide, but is more
common in Europe, Australia, and New
Zealand.Sunday, April 26, 2015 35
Aetiology and Pathogenesis
The cause is unknown.
However, both genetic and environmental
factors (Paramyxovirus) have been implicated.
Paramyxovirus is thought to induce the
secretion of IL-6 from fibroblasts and
IL-6 recruits and activates osteoclasts.
Three phases of Paget disease have been
described: lytic, mixed lytic and blastic, and
sclerotic.Sunday, April 26, 2015 36
Aetiology and Pathogenesis……….
1. Paget disease begins with the lytic phase, in
which normal bone is resorbed by osteoclasts.
2. The second phase, the mixed phase, is
characterized by rapid increases in bone
formation from numerous osteoblasts.
3. In the final phase of Paget disease, the
sclerotic phase, bone formation dominates
and the bone that is formed has a disorganized
pattern (woven bone) and is weaker than
normal adult bone.Sunday, April 26, 2015 37
Age - People older than 40.
Sex - Men are more commonly affected.
Race – whites are more affected.
Family history - close relative with Paget's
disease of bones.
Sunday, April 26, 2015 38
Signs and symptoms
Depend on the part of your body
Pelvis - hip pain.
Skull - An overgrowth of bone in
the skull can cause hearing loss or
Spine - nerve roots can become
compressed. This can cause pain,
tingling and numbness in an arm or
Leg - As the bones weaken, they
may bendSunday, April 26, 2015 39
Fractures - Bones break more easily.
Osteoarthritis - Distorted bones can increase the
amount of stress on nearby joints, which can cause
Heart failure - Paget's disease may force the heart to
work harder to pump blood to the affected areas.
In people with pre-existing heart disease, this
increased workload can lead to heart failure.
Hearing loss - caused by narrowing of the auditory
foramen or direct involvement of the bones of the
Bone cancer. Bone cancer occurs in less than 1
percent of people with Paget's disease.Sunday, April 26, 2015 40
Benign bone tumors
Osteochondroma is the most common benign
tumor of bone.
This bone growth is covered by a cap of
cartilage projecting from the surface of a bone.
It occurs most frequently in men younger than
25 years of age.
Sunday, April 26, 2015 41
MALIGNANT BONE TUMORS
This is the most common primary malignant
tumor of bone.
The peak incidence is in males 10 to 20 years of
The tumor occurs most frequently in the
metaphysis of long bones.
Sunday, April 26, 2015 42
1. Paget disease of bone, fibrous dysplasia,
2. Ionizing radiation
3. Bone infarcts
4. Familial retinoblastoma presumably due to
loss of the Rb suppressor gene locus on
chromosome 13.Sunday, April 26, 2015 43
Pain and swelling and occasionally pathologic
A two- to three-fold increase of serum
Lifting of the periosteum by the expanding
tumor, which creates a characteristic radiologic
appearance known as the Codman triangle.
Early hematogenous spread to the lungs,
liver, and brain
Sunday, April 26, 2015 44
Grossly, osteosarcomas are gray-white
tumors, often exhibiting hemorrhage
and cystic degeneration.Sunday, April 26, 2015 45
This is a malignant cartilaginous tumor.
The peak incidence is in men 30 to 60 years of
The neoplasm may arise as a primary tumor or
from transformation of preexisting cartilaginous
Characteristic sites of origin include the pelvis,
spine, or scapula; the proximal humerus or
proximal femur or tibia near the knee.
Sunday, April 26, 2015 46
Sunday, April 26, 2015 47