PATHOLOGY OF THE MUSCULOSKELETAL SYSTEM

BY

CHAPIMA F.MSc. PTH - Clinical Pathology (UNZA), B.Sc. (UNZA)

Sunday, April 26, 2015 1

Lecture outline

Bones

Congenital diseases of bone

Acquired diseases of bone development

Fractures

Osteonecrosis

Osteomyelitis

Metabolic bone disease

Bone tumorsSunday, April 26, 2015 2

CONGENITAL DISEASES OF BONE

1. Osteogenesis Imperfecta

Definition

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

bones.Sunday, April 26, 2015 3

Clinical features

Type I

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.

Triangular face.

Hearing loss possible, often beginning in early

20s or 30s.Sunday, April 26, 2015 4

Clinical features…………..

Type II

Most severe form.

Numerous fractures and

severe bone deformity.

Small stature with

underdeveloped lungs.

Sunday, April 26, 2015 5

Clinical features…………..

Type III

Short stature.

Barrel-shaped rib cage.

Bone deformity, oftensevere.

Brittle teeth possible.

Hearing loss possible.

Sunday, April 26, 2015 6

2. Achondroplasia

Achondroplasia means "without cartilage

formation,“.

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

Causes

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

Clinical features

Clients have short stature

The average height of an adult

male is 131 cm adult females is 124

cm.

Have an average-size trunk,

Short arms and legs with particularly

short upper arms and thighs,

Limited range of motion at the

elbows

A big head (macrocephaly) with a

prominent forehead.Sunday, April 26, 2015 9

ACQUIRED DISEASES OF BONE DEVELOPMENT

1. Fractures

A fracture is a broken bone. A bone may be

completely fractured or partially fractured in any

number of ways.

Cause

The most common causes of fractures are:

Trauma. A fall, a motor vehicle accident, or

trauma during a football game can all result in

fractures.Sunday, April 26, 2015 10

Cause…………..

Osteoporosis. This disorder weakens bones

and makes them more likely to break

(pathological fractures).

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 …………..

Transverse fracture.

This type of fracture has

a horizontal fracture line.

Oblique fracture. This

type of fracture has an

angled pattern.

Comminuted fracture.

In this type of fracture,

the bone shatters into

three or more pieces.Sunday, April 26, 2015 13

Symptoms

Pain on the affected area

Un able to move the injuredlimb.

Other common symptomsinclude:

Swelling and tendernessaround the injury area

Bruising

Deformity — a limb may look"out of place" or a part of thebone may puncture throughthe skinSunday, April 26, 2015 14

2. Osteonecrosis

Osteonecrosis (ON) is a focal infarct of bonethat may be caused by specific etiologic factorsor may be idiopathic.

Causes/ Risk factors

No one is sure what causes the disease.

Risk factors include;

Long-term steroid treatment

Alcohol abuse

Joint injuries

Having diseases such as arthritis and cancerSunday, April 26, 2015 15

Pathophysiology

Mechanisms of non-traumatic ON include

embolization by blood clots or lipid droplets.

This leads to the death of osteocytes and bone

marrow.

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

Pathophysiology…………..

However, in some patients,

the process is not successful

and the infarct gradually

collapses.

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

3. Osteomyelitis

Osteomyelitis is an infection in a bone.

Causes

Most cases of osteomyelitis are caused byStaphylococcus aureus (PyogenicOsteomyelitis) and Mycobacteriumtuberculosis (Tuberculous Osteomyelitis)

Micro – organisms can enter a bone in 3 ways;

Via the bloodstream. infection in other partsof the body — for example pneumonia or aurinary tract infection — can travel throughbloodstream to a bone.Sunday, April 26, 2015 19

Causes…………..

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

of fractures.

Direct contamination can also occur during

surgeries to replace joints or repair fractures.Sunday, April 26, 2015 20

Risk factors

Recent injury or orthopedic surgery

Poorly controlled diabetes

Peripheral arterial disease, often related to

smoking

Sickle cell disease

Chemotherapy

Sunday, April 26, 2015 21

Pathophysiology

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 youngchildren

Localized bone pain

Swelling, warmth and rednessover the area of the infection

Sometimes osteomyelitis causesno signs and symptoms or hassigns and symptoms that aredifficult to distinguish fromother problems.Sunday, April 26, 2015 23

Complications

Osteonecrosis - Bone death

Septic arthritis

Impaired growth

Skin cancer. If osteomyelitis has resulted in an

open sore that is draining pus, the surrounding

skin is at higher risk of developing squamous

cell cancer.

Sunday, April 26, 2015 24

METABOLIC BONE DISEASE

1. Osteoporosis

Osteoporosis AKA “porous bone” is a

disease characterized by increased sponginess

of the skeleton resulting from reduced bone

mass.

Sunday, April 26, 2015 25

Classifications

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

cortical bone.

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

Pathophysiology

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

as prostaglandins.

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

Pathophysiology………..

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

Pathophysiology………..

Sunday, April 26, 2015 29

Risk Factors

Race (Caucasians > African Americans)

Sex (F > M)

Physical inactivity

Slender body build

Early menopause

Increasing age

Calcium nutritional state - insufficient dietary

intake.

Sunday, April 26, 2015 30

Signs and Symptoms

Patients with osteoporosis

are asymptomatic unless a

fracture has occurred.

Gross morphology

The trabecular plates

become perforated,

thinned, and lose their

interconnections, leading

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

adults.

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

Pathophysiology

Vitamin D promotes the absorption of

calcium and phosphorus from the

gastrointestinal tract.

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

legs.

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

macrophages

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

Risk factors

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

that's affected;

Pelvis - hip pain.

Skull - An overgrowth of bone in

the skull can cause hearing loss or

headaches.

Spine - nerve roots can become

compressed. This can cause pain,

tingling and numbness in an arm or

leg.

Leg - As the bones weaken, they

may bendSunday, April 26, 2015 39

Complications

Fractures - Bones break more easily.

Osteoarthritis - Distorted bones can increase theamount of stress on nearby joints, which can causeosteoarthritis.

Heart failure - Paget's disease may force the heart towork harder to pump blood to the affected areas.

In people with pre-existing heart disease, thisincreased workload can lead to heart failure.

Hearing loss - caused by narrowing of the auditoryforamen or direct involvement of the bones of themiddle ear.

Bone cancer. Bone cancer occurs in less than 1percent of people with Paget's disease.Sunday, April 26, 2015 40

BONE TUMORS

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

1. Osteosarcoma

This is the most common primary malignant

tumor of bone.

The peak incidence is in males 10 to 20 years of

age.

The tumor occurs most frequently in the

metaphysis of long bones.Sunday, April 26, 2015 42

Predisposing factors

1. Paget disease of bone, fibrous dysplasia,

chondroma, osteochondroma

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

Clinical characteristics

Pain and swelling and occasionally pathologic

fracture

A two- to three-fold increase of serum

alkaline phosphatase

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 brainSunday, April 26, 2015 44

Gross morphology

Grossly, osteosarcomas are gray-white tumors, often exhibiting hemorrhageand cystic degeneration. Sunday, April 26, 2015 45

Chondrosarcoma

This is a malignant cartilaginous tumor.

The peak incidence is in men 30 to 60 years of

age.

The neoplasm may arise as a primary tumor or

from transformation of preexisting cartilaginous

tumors

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

Chondrosarcoma ……………..

Sunday, April 26, 2015 47

REFERENCES AND CREDITS

Robbins, S.L, Kumar, V and Abbas, K (2010). Pathologic Basis of

Disease (8th Edition). W.B Saunders Company, Philadelphia.

Robbins SL and Kumar V (2007). Basic Pathology (8th Edition).WB

Saunders Co. London.

Harsh Mohan, (2010). Textbook of Pathology (6th Edition). Jaypee

brothers medical publishers (p) ltd, India

Riede and Werner, Color Atlas of Pathology © 2004 Thieme

Rubin E, Rubin R, Strayer D.S. (2012) Rubin`s Pathology:

Clinicopathologic Foundations of Medicine (6th Edition), Lippincott

Williams & Wilkins, a Wolters Kluwer business. Philadelphia, PA.

Sunday, April 26, 2015 48