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

Senility due to age-related decrease in .1

osteoblastic activity (.)senile osteoporosis

Estrogen deficiency, mainly due to increased .2

osteoclastic activity (postmenopausal
.(osteoporosis

Excessive production or administration of adrenal .3

cortical hormones, due to decreased osteoblastic
.activity

Local factors e.g poliomyelitis, paraplegia or .4

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

Bone pains .1

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

Pathological fractures .3
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

Defective bone remodeling with .1

persistence of woven bone

Marked thickening of bone cortices and .2

trabeculae with marked narrowing of
marrow spaces

Narrowing of neural foramina with .3

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

Early in the disease, there is .1

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
Later on, bone resorption gradually .2
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

(Bone deformity (see above .1

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

Delayed closure of skull sutures and .2

fontanelles

Delayed eruption of teeth .3

(Thinning of occipital bones (craniotabes .4

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

Rickety rosary: The chest appears .6

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

Harrison's sulcus: A transverse groove on .7

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

In females, this may lead to difficult

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

Swelling of wrists, ankles and .11

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

Pot belly due to flabbiness of abdominal muscles .1

Enlargement of spleen and lymph nodes .2

Anemia .3

Low serum calcium and phosphorus .4

:Complications and causes of death

Gastroeneteritis .1

Bronchopneumonia .2
: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

Increased osteoclasts .1

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

Tumor-like masses composed of fibrous tissue, .3

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

Bone pains .1

Bone swellings .2

Pathological fractures .3

Hypercalcemia, hypophosphatemia and .4

increased serum alkaline phosphatase

Renal calculi .5
:RENAL OSTEODYSTROPHY

Bony changes seen in patients with

chronic renal failure particularly
.those receiving dialysis
:Pathogenesis

Mobilization of calcium from bone due to .1

secondary hyperparathyroidism consequent to
phosphate retention resulting from decreased
glomerular filtration

Inadequate production of active vitamin D .2

metabolites by the failing kidneys

:Deposition of aluminum in bone, derived from .3

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

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

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

Increased bone density (osteosclerosis) due to .3

excessive formation of woven bone in 30% of
patients

Amyloid deposition in bone and periarticular .4

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

.1Staph. aureus: The commonest

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

influenzae, Proteus, Pneumococci, typhoid
bacilli
:Predisposing factors

Trauma: This leads to a hematoma .1

which provides a good medium for
bacterial growth

Age and sex: Male children and .2

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

Blood borne infection from a septic focus .1

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

Local spread of infection from a nearby .2

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

Direct infection of bone through a .3

compound (open) fracture
:Bones affected

In acute .1hematogenous osteomyelitis, the

metaphyses of long bones are the
.commonest site of affection

In .2non-hematogenous osteomyelitis,any
bony site. can be affected
Pathology of acute hematogenous
:osteomyelitis

A localized suppurative inflammation (abscess) .1

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

Thrombosis then occurs in the penetrating .3

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
As the infection becomes less acute, new .4
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 multiplesinuses
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

Acute toxemia .1

Septicemia which may lead to acute bacterial .2

endocarditis

Pyemia due to septic thrombophlebitis .3

Pathological fracture .4

Chronicity .5

Sympathetic effusion in nearby joints .6

Suppurative arthritis due to local spread of .7

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

Pathological fracture .1

Secondary amyloidosis .2

Squamous cell carcinoma developing in a skin .3

sinus
:BRODIE'S ABSCESS

A localized chronic osteomyelitis that

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

This isalways secondary and usually results

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

The tuberculous reaction leads to caseation

andbone 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 thelower dorsal

)thoracic) and upper lumbar vertebrae.
Infection usually starts in asingle 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

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

form of kyphosis, lordosis or scoliosis

Paraplegia due to compression of the spinal cord by .2

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

:Cold abscess in .3
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

Miliary tuberculosis .4

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

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

A benign tumor composed of woven or lamellar

.bone

Itdevelops most commonly in cranial and facial

.bones

It appearsgrossly 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 thecommonest primary malignant bone

.tumor

It occurs most commonly between the ages

of10 and 25 years, particularly in males.
Cases occurringafter the age of 40 years
are usually preceded by Paget's disease of
.bone or bone irradiation
:Gross appearance

Thecommonest site of osteosarcoma is

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

Itappears 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
In the .1osteoblastic )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
In the .2osteolytic 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
In the .3telangiectatic type

which is highly vascular, the

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

:Osteosarcoma consists of

.1Malignant osteoblasts which may be polygonal,

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

.2A stroma containing variable amounts of osteoid,

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

Direct (local) spread to periosteum, .1

surrounding muscles and marrow cavity

Blood (hematogenous) spread to lungs .2

and other organs. This occurs early

Lymphatic spread. This is rare and late .3

:CARTILAGE FORMING TUMORS

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

Itarises most commonly from themetaphysis of

long bones near the epiphyseal plate

and appearsgrossly 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 achondosarcoma,
.particularly when multiple
:Chondroma

A benign tumor composed of hyaline

.cartilage

Itoccurs most commonly in theshort

.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 achondrosarcoma,
.particularly when multiple
:Chondrosarcoma

.A malignant cartilaginous tumor

It occurs most commonly inadults

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

Thecommonest sites of chondrosarcoma are the

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

Itappears grossly as a firm to hard, lobulated,

translucent, bluish-gray mass that destroys and
replaces the bone.Focal calcification is common
and constitutes and importantradiological 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 ofmalignant cartilage

. cells anda 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

.Local to surrounding tissue .1

Blood spread to lungs and other .2

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

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

A benigntumor-like lesion ofunknown etiology that

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

It occursmost commonly in children and usually

.affects the ribs, jaw, femur and tibia

Microscopically, it consists of fibrous tissue

interspersed bythin, branching or curved
trabeculae ofwoven bone thatlack osteoblastic
rimming. It may rarely change to a malignant
.fibrous histiocytoma
:MISCELLANEOUS TUMORS

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

Ahighly malignant tumor ofneuroectodermal

.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 of10

and 25 years

. and usually affects thediaphyses 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

Local to surrounding tissues .1

Hematogenous to lung and other .2

organs includingother 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 probablyarises

from the fibroblast or monocyte rather
than the osteoclast

It occurs most commonly between20-40

years of age
:Gross appearance

The commonestsites are theepipyhses 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

Itappears grossly as a soft grayish mass

,that replaces & expands the epiphysis
surrounded by a thin shell of cortical bone
that gives a sensation ofegg-shell
cracklingon 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

Numerous .1osteoclasts appearing as

large cells with many nuclei

Plump, .2oval or spindly cells

:Behavior

(Most cases are benign (grade I tumors .1

Some cases are locally malignant and frequently .2

(recur after removal (grade II

Rare cases are frankly malignant and may .3

metastasize to the lungs. These shownuclear
pleomorphism andfrequent mitosis in the
oval/spindly cells and adecreased number of
osteoclasts( (grade III
:METASTATIC TUMORS

Commoner than primary tumors

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

Carcinomas, particularly thyroid, breast, .1

lung, stomach, kidney, suprarenal and
prostatic carcinomas

Various sarcomas .2

Childhood tumors e.g. neuroblastoma, .3

Wilms’ tumor, rhabdomyosarcoma and
Ewing’s sarcoma

Choriocarcinoma and malignant .4

melanoma
:Effects

Bone destruction leading to .1bone pains

and tenderness , pathological fracture
and hypercalcemia

Reactive new bone formation: This is .2rare

and is typically seen in metastatic
carcinoma of the prostate

Anemia due to bone marrow replacement .3