DISEASES OF

BONES
Diseases Associated
with Abnormal Bone
Matrix
OSTEOGENESIS IMPERFECTA (TYPE I
COLLAGEN DISEASE):

A group of mainly autosomal dominant genetic disorders

resulting from defective synthesis of type I collagen due to
mutations in the gene for type I collagen .

Affected bones have thin bone cortices and trabeculae and

are markedly fragile and easily broken.

In addition to bone, other tissues rich in type I collagen are

also affected e.g. sclerae, teeth ears, joints and skin
OSTEOPOROSIS:

A condition in which the bone mass is

reduced below the level necessary
for normal bone function.
Pathogenesis: An excess of bone
resorption over bone formation due
to increased resorption, decreased
formation or both.
Causes:

1. Senility due to age-related decrease in

osteoblastic activity (senile osteoporosis).

2. Estrogen deficiency, mainly due to increased

osteoclastic activity (postmenopausal
osteoporosis).

3. Excessive production or administration of adrenal

cortical hormones, due to decreased osteoblastic
activity.

4. Local factors e.g poliomyelitis, paraplegia or

immobilization of fractured bones, due to
decreased mechanical stimulation of osteoblastic
activity.
Pathology:
Variable thinning of bone
cortices and trabeculae
with normal bone
mineralization.
Effects/Complications:

1. Bone pains

2. Reduced height or
even kyphosis, due
to vertebral collapse

3. Pathological fractures
following minor trauma,
mainly in neck of femur
and pelvic bones
Diseases due to osteoclastic
dysfunction
OSTEOPETROSIS:

A goup of genetic disorders resulting

from osteoclastic dysfunction leading
to diffuse bone sclerosis.

The sclerotic bones are, however,

fragile and easily fractured.
Pathology:

1. Defective bone remodeling with

persistence of woven bone

2. Marked thickening of bone cortices and

trabeculae with marked narrowing of
marrow spaces

3. Narrowing of neural foramina with

compression of exiting nerves
PAGET'S DISEASE OF BONE (OSTEITIS
DEFORMANS):

A rare disease that probably results from

osteoclastic dysfunction due to a slow
virus infection by a paramyxovirus.

The disease appears after the age of 40

years and may be familial.

It is usually generalized affecting the leg

bones, vertebrae and skull but may rarely
be localized affecting mainly the tibia.
Pathology:

1. Early in the disease, there is

increased osteoclastic bone
resorption with replacement of the
affected bones by poorly mineralized
osteoid and highly vascularized
fibrous tissue leading to bone
softening and deformity with
kyphosis and bowing of leg bones
(osteolytic phase).
2. Later on, bone resorption gradually
decreases and bone formation
progressively increases leading
eventually to thickening and
hardening of the deformed bones
and the skull (osteoblastic phase).
Microscopic examination of bone at
this stage shows thickened bone
trabeculae with a characteristic
mosaic (jigsaw puzzle) appearance.
Effects/Complications:

1. Bone deformity (see above)

2. Bone pains
3. Pathological fractures
4. Osteoarthritis due to abnormal stresses on the
joints by the bone deformity
5. Deafness due to compression of the 8th cranial
nerve by narrowed exit foramina in the skull
6. Spinal cord compression by thickened
vertebral bodies
7. Osteosarcoma in 1% of cases
8. High output cardiac failure due to increased
venous return from the abnormal bones
9. Increased serum alkaline phosphatase
 Disease associated with
Abnormal Bone Mineralization
RICKETS:

A bony disease of infants (6 months –

2 years) resulting from vitamin D
deficiency, most commonly due to
lack of exposure to ultraviolet rays of
the sun (which changes
subcutaneous sterols to vitamin D).
Bony manifestations:

These result from failure of

mineralization of bone with
accumulation of excessive osteoid on
the surface of bone trabeculae
leading to abnormally soft bones.
They include:
1. Thickening of frontal and parietal bones
of the skull (bossing)

2. Delayed closure of skull sutures and

fontanelles

3. Delayed eruption of teeth

4. Thinning of occipital bones (craniotabes)

5. Pigeon chest: The sternum is pushed
forwards with a longitudinal groove on
each side

6. Rickety rosary: The chest appears

"beaded" on each side due to enlargement
of the costochondral junctions

7. Harrison's sulcus: A transverse groove on

each side of the chest corresponding to
the insertion of the diaphragm in the rib
8. Deformity of the lumbar vertebrae
in the form of kyphosis, lordosis
or scoliosis
9. Narrow pelvic inlet: The sacral
promontory is pushed forwards
and the acetabula inwards.

In females, this may lead to difficult

labor later on
10. Bowing of long bones (femur, tibia,
radius, ulna)

11. Swelling of wrists, ankles and

knees due to widening of the
epiphyseal plates
12. Microscopically there is:

a) Increased osteoid
on surfaces of poorly
mineralized bone
trabeculae

b) Irregular thickening of the epiphyseal

plates due to failure of osteoclastic
resorption of cartilage (consequent to
failure of mineralization of the carilage
matrix)
Extra-skeletal manifestations:

1. Pot belly due to flabbiness of abdominal muscles

2. Enlargement of spleen and lymph nodes

3. Anemia

4. Low serum calcium and phosphorus

Complications and causes of death:

1. Gastroeneteritis

2. Bronchopneumonia
OSTEOMALACIA:

A bony disease of adults resulting from

deficiency of vitamin D and calcium.

It usually occurs in females following

repeated pregnancies and

is characterized by deformities of long bones

and vertebrae and narrow pelvic inlet,
consequent to bone softening.
OSTEITIS FIBROSA CYSTICA (von
RECKLINGHAUSEN'S DISEASE OF BONE):

A bony disease resulting from excessive

secretion of parathyroid hormone by
hyperplasia or adenoma of the parathyroid
glands.

Parathyroid hormone leads mobilization of

calcium and phosphate from bone and
increased resorption of calcium from the
bowel.
Pathology:

Generalized bone decalcification and resorption

associated with:

1. Increased osteoclasts

2. Focal replacement of
bone by fibrous tissue
that commonly undergoes
cystic degeneration

3. Tumor-like masses composed of fibrous tissue,

abundant hemosiderin and numerous
osteoclasts (brown tumors)
Effects/Complications:

1. Bone pains

2. Bone swellings

3. Pathological fractures

4. Hypercalcemia, hypophosphatemia and

increased serum alkaline phosphatase

5. Renal calculi
RENAL OSTEODYSTROPHY:

Bony changes seen in patients with

chronic renal failure particularly
those receiving dialysis.
Pathogenesis:

1. Mobilization of calcium from bone due to

secondary hyperparathyroidism consequent to
phosphate retention resulting from decreased
glomerular filtration

2. Inadequate production of active vitamin D

metabolites by the failing kidneys

3. Deposition of aluminum in bone, derived from:

a) Dialysis solutions prepared from water with a
high aluminum content
b) Aluminum-containing oral phosphate binders
Pathology: The following changes may be seen
separately or in variable combinations:

1. Osteitis fibrosa cystica in 80 – 90% of patients

2. Rickets/osteomalacia in 20 – 40% of patients

3. Increased bone density (osteosclerosis) due to

excessive formation of woven bone in 30% of
patients

4. Amyloid deposition in bone and periarticular

tissues in some patients
Bone Infections
(Osteomyelitis)
ACUTE SUPPURATIVE OSTEOMYELITIS:

Acute suppurative inflammation of bone and

its soft tissues, namely, periosteum,
Haversian canals and bone marrow

Causative organisms:

1. Staph. aureus: The commonest

2. Other organisms: Streptococci, E. coli, H.

influenzae, Proteus, Pneumococci, typhoid
bacilli
Predisposing factors:

1. Trauma: This leads to a hematoma

which provides a good medium for
bacterial growth

2. Age and sex: Male children and

adolescents are most commonly
affected
Routes (modes) of infection:

1. Blood borne infection from a septic focus

elsewhere in the body e.g skin boil,
tonsillitis. This is the commonest mode of
infection leading to "acute
hematogenous osteomyelitis"

2. Local spread of infection from a nearby

focus of suppuration e.g dental abscess,
suppurative otitis media

3. Direct infection of bone through a

compound (open) fracture
Bones affected:

1. In acute hematogenous osteomyelitis, the

metaphyses of long bones are the
commonest site of affection.

2. In non-hematogenous osteomyelitis, any

bony site can be affected.
Pathology of acute hematogenous
osteomyelitis:

1. A localized suppurative inflammation (abscess)

develops in the metaphysis from which infection
rapidly spreads to the bone marrow cavity and
along the Haversian canals to the
periosteum.
2. Infection of the periosteum is rapidly followed by
accumulation of pus underneath the periosteum
i.e. formation of a subperiosteal abscess.

3. Thrombosis then occurs in the penetrating

arteries leading to ischemic necrosis of a
variable portion of the bone which becomes
gradually separated from the surrounding viable
bone by osteoclastic activity. The necrotic bone is
called "sequestrum".
4. As the infection becomes less acute, new
bone is formed by the irritated
osteoblasts, particularly subperosteally.
The subperiosteal new bone forms a shell
around the sequestrum, known as
"involucrum". The involucrum is often
interrupted by irregular openings known
as "cloacae" through which pus is
discharged and may dissect its way to
open through the skin by multiple sinuses.
N.B. Infection does not usually spread to
nearby joints because:

a) The epiphyseal cartilage provides a

mechanical barrier against spread of
infection from the metaphysis.

b) The periosteum is firmly attached to the

margin of the epiphyseal cartilage
preventing spread of infection from the
subperiosteal abscess.
Complcations:

1. Acute toxemia

2. Septicemia which may lead to acute bacterial

endocarditis

3. Pyemia due to septic thrombophlebitis

4. Pathological fracture

5. Chronicity

6. Sympathetic effusion in nearby joints

7. Suppurative arthritis due to local spread of

infection to joints where the metaphysis is partly
intra-articular e.g hip and shoulder joints
NONSPECIFIC CHRONIC OSTEOMYELYTIS:

This follows acute suppurative osteomyelitis and is

characterized by thickened deformed bones with
cloacae and skin sinuses discharging pus.

Complications:

1. Pathological fracture

2. Secondary amyloidosis

3. Squamous cell carcinoma developing in a skin

sinus
BRODIE'S ABSCESS:

A localized chronic osteomyelitis that

occurs most commonly in the upper
tibial metaphysis. It appears as a
small cavity filled with pus or serous
fluid and surrouned by reactive
sclerotic bone.
TUBERCULOUS OSTEOMYELITIS:

This is always secondary and usually results

from hematogenous dissemination of
infection from a tuberculous focus in the
lungs, lymph nodes or urinary tract.

The tuberculous reaction leads to caseation

and bone destruction with only little or NO
new bone formation. Any bone can be
affected but the commonest sites are the
vertebrae.
Tuberculosis of the Spine (Pott's
Disease):

This develops most commonly in the lower dorsal

(thoracic) and upper lumbar vertebrae.
Infection usually starts in a single vertebral
body leading to caseation and bone
destruction, then spreads:

a) through the inter-vertebral discs to involve other

vertebral bodies, and

b) to the nearby soft tissues leading to localized

accumulations of caseous material known as
cold abscesses.
Complications:

1. Deformity of the spine due to vertebral collapse, in the

form of kyphosis, lordosis or scoliosis

2. Paraplegia due to compression of the spinal cord by

caseous material and necrotic bone fragments derived from
the diseased vertebral bodies

3. Cold abscess in:

a) Retropharyngeal space or posterior triangle of the neck
(cervical vertebrae)
b) Intercostal space along a rib (thoracic vertebrae)
c) Psoas sheath (psoas abscess), inguinal region or even
popleteal fossa (lumbar vertebrae)

4. Miliary tuberculosis

5. Secondary amyloidosis
Bone Tumors and Tumor-like
Conditions
BONE FORMING TUMORS:

These include:
1. Osteoma
2. Osteoid osteoma
3. Benign osteoblastoma
4. Osteosarcoma .
Osteoma:

A benign tumor composed of woven or lamellar

bone.

It develops most commonly in cranial and facial

bones.

It appears grossly as a hemisphecal hard mass that

bulges underneath the periosteum or endosteum.
It is usually solitary but multiple osteomas occur
in Gardner's syndrome (an autosomal dominant
disorder characterized by multiple osteomas,
intestinal adenomatous polyps, epidermal cysts
and fibromatosis).
Osteosarcoma (osteogenic sarcoma):

A malignant mesenchymal tumor in which

the neoplastic cells form osteoid or
calcified bone matrix.

It is the commonest primary malignant bone

tumor.

It occurs most commonly between the ages

of 10 and 25 years, particularly in males.
Cases occurring after the age of 40 years
are usually preceded by Paget's disease of
bone or bone irradiation.
Gross appearance:

The commonest site of osteosarcoma is

metaphysis of long bones, particularly
around the knee joint, although any bone
can be affected.

It appears grossly as a fusiform mass that

destroys and replaces the bone and often
elevates and infiltrates the periosteum. It
may also infiltrate the surrounding skeletal
muscle. The consistency and color vary
according to the microscopic (histologic)
type of the tumor:
1. In the osteoblastic (osteosclerotic) type

in which the neoplastic cells form excessive bone

matrix, the consistency is firm to hard and the
color is grayish.

The neoplastic bone often forms spicules that run

perpendicular to the long axis of the bone giving
a characteristic "sun ray appearance" in X-ray
films.

Another characteristic X-ray finding is the

"Codman's triangle" resulting from the
deposition of reactive subperiosteal bone in the
angle between the bone and the elevated
periosteum.
2. In the osteolytic type

in which there is only little or

practically no new bone formation,
the consistency is soft and the cut
surface is pinkish-grayi with areas of
necrosis and hemorrhage.
3. In the telangiectatic type

which is highly vascular, the

consistency is soft and the color is
purplish-red.
Microscopic appearance:

Osteosarcoma consists of:

1. Malignant osteoblasts which may be polygonal,

spindly or multinucleated and show variable
nuclear pleomorphism and mitotic activity
depending on the grade of the tumor

2. A stroma containing variable amounts of osteoid,

calcified bone matrix, cartilage, fibrous tissue
and blood vessels depending on the histologic
type of the tumor
Spread:

1. Direct (local) spread to periosteum,

surrounding muscles and marrow cavity

2. Blood (hematogenous) spread to lungs

and other organs. This occurs early

3. Lymphatic spread. This is rare and late

CARTILAGE FORMING TUMORS:

These include:
1. Osteochondroma (exostosis)
2. Chondroma
3. Benign chondroblastoma
4. Condromyxoid fibroma
5. Chondrosarcoma
Osteochondroma (exostosis):
A benign developmental tumor-like lesion consisting
of bone and hyaline cartilage.

It arises most commonly from the metaphysis of

long bones near the epiphyseal plate

and appears grossly as a bony mass covered by a

cap of cartilage and attached to the bone by a
pedicle. It is usually solitary but multiple
exostosis are inherited as an autosomal dominant
disease. It may rarely undergo malignant
transformation into a chondosarcoma,
particularly when multiple.
Chondroma:

A benign tumor composed of hyaline

cartilage.

It occurs most commonly in the short

tubular bones of the hands and feet.

It is usually solitary but multiple

chondromas occur in Ollier's disease. It
may rarely undergo malignant
transformation into a chondrosarcoma,
particularly when multiple.
Chondrosarcoma:

A malignant cartilaginous tumor.

It occurs most commonly in adults

between the ages of 30 and 60
years, particularly in males.

It usually arises do novo but may

rarely arise from a pre-existing
exostosis or chondroma.
Gross appearance:

The commonest sites of chondrosarcoma are the

pelvic bones, ribs, shoulder girdle and proximal
femur or humerus.

It appears grossly as a firm to hard, lobulated,

translucent, bluish-gray mass that destroys and
replaces the bone. Focal calcification is common
and constitutes and important radiological sign.
There may be also myxomatous degeneration
and necrosis.
The mass may be located within the medullary
cavity (central or intramedullary
chondrosarcoma) or on the surface of the bone
(peripheral or juxtacortical chondosarcoma).
Microscopic appearance:

Chondrosarcoma consists of malignant cartilage

cells and a cartilaginous matrix.

Low grade chondrosarcomas may be so well

diffrentiated and, hence, difficult to distinguish
from benign chondromas. In such cases, clinical
and radiological features may be more important
for differentiation than microscopic examination.

High grade chondrosarcomas, on the other

hand, show marked nuclear pleomorphism,
multinucleate tumor giant cells and frequent
mitosis and may be difficult to differentiate from
other high grade sarcomas.
Immunohistochemistry may help in such cases.
Spread:

1. Local to surrounding tissue.

2. Blood spread to lungs and other

organs, mainly in high grade
tumors
FIBROUS AND FIBRO-OSSEOUS
TUMORS:

These include:
1. Fibrous cortical defect and non-ossifying
fibroma
2. Fibrous dysplasia
3. Fibrosarcoma
4. Malignant fibrous histiocytoma
Fibrous dysplasia:

A benign tumor-like lesion of unknown etiology that

may involve a single bone (monostotic type) or
multiple bones (polyostotic type).

It occurs most commonly in children and usually

affects the ribs, jaw, femur and tibia.

Microscopically, it consists of fibrous tissue

interspersed by thin, branching or curved
trabeculae of woven bone that lack osteoblastic
rimming. It may rarely change to a malignant
fibrous histiocytoma.
MISCELLANEOUS TUMORS:

These include:
1. Ewing’s sarcoma
2. Osteoclastoma
3. Multiple myeloma
4. Non-Hodgkin’s lymphoma
Ewing' s sarcoma:

A highly malignant tumor of neuroectodermal

origin.

Virtually all of these tumors have a reciprocal

translocation between chromosomes 11 and 22
[t(11;22)].

It occurs most commonly between the ages of 10

and 25 years

and usually affects the diaphyses of long bones.

Gross appearance:

A soft grayish mass that infiltrates and

replaces the bone, surrounded by
parallel layers of reactive
subperiosteal bone that gives a
characteristic "onion skin"
appearance in X-ray films.
Microscopic appearance:

Sheets of uniform small round cells

with hyperchromatic nuclei and
scanty cytoplasm containing
glycogen.
Clinical features:

Bone swelling and pain, sometimes

accompanied by fever, leucocytosis
and increased ESR, a picture that
may resemble osteomyelitis.
Spread:

1. Local to surrounding tissues

2. Hematogenous to lung and other

organs including other bones
Osteoclastoma (Giant Cell Tumor of
Bone):

A bone tumor characterized by presence of

numerous osteoclastic giant cells

Its origin is not settled but it probably arises

from the fibroblast or monocyte rather
than the osteoclast

It occurs most commonly between 20-40

years of age
Gross appearance:

The commonest sites are the epipyhses of

long bones, particularly the lower end of
the femur, the upper end of the tibia, the
upper end of the humerus and the lower
end of the radius

It appears grossly as a soft grayish mass

that replaces & expands the epiphysis,
surrounded by a thin shell of cortical bone
that gives a sensation of egg-shell
crackling on palpation
X-ray Appearance:

A characteristic “soap bubble”

appearance due to persistence of
variable amounts of thin bone
trabeculae within the tumor
Microscopic appearance:

Consists of

1. Numerous osteoclasts appearing as

large cells with many nuclei

2. Plump, oval or spindly cells

Behavior:

1. Most cases are benign (grade I tumors)

2. Some cases are locally malignant and frequently

recur after removal (grade II)

3. Rare cases are frankly malignant and may

metastasize to the lungs. These show nuclear
pleomorphism and frequent mitosis in the
oval/spindly cells and a decreased number of
osteoclasts (grade III)
METASTATIC TUMORS:

Commoner than primary tumors

and occur most commonly in sites
rich in red bone marrow e.g.
vertebrae, ribs and proximal
humerus and femur.
Results most commonly from
hematogenous dissemination of:

1. Carcinomas, particularly thyroid, breast,

lung, stomach, kidney, suprarenal and
prostatic carcinomas

2. Various sarcomas

3. Childhood tumors e.g. neuroblastoma,

Wilms’ tumor, rhabdomyosarcoma and
Ewing’s sarcoma

4. Choriocarcinoma and malignant

melanoma
Effects:

1. Bone destruction leading to bone pains

and tenderness, pathological fracture
and hypercalcemia

2. Reactive new bone formation: This is rare

and is typically seen in metastatic
carcinoma of the prostate

3. Anemia due to bone marrow replacement