Paget's

Disease &
Osteopetrosis
:By
Mohammed Badr Alddin Mohammed
Master Degree by Courses
Program
University of Khartoum
Batch (1)

What is Paget's Disease

Paget's disease is a chronic disease that leads

to enlarged and misshapen bones. The bone's
remodeling is disturbed and not synchronized.
This causes the bone to be enlarged, not as
dense, and brittle. The disease becomes more
.common with age

What Causes Paget's

It is not entirely known what causes Paget's

disease. However, certain genes have been
associated with it such as the
Sequestrosome 1 gene on chromosome 5. Also,
viral infection may be necessary to trigger the
.disease in people who have inherited the gene

Symptoms

Most of the time there are no symptoms and it is

often found on x rays taken for another reason.
Paget's disease can cause bone-pain, deformity,
fractures and arthritis. The pain is located in the
affected bone.The most common bones affected
are the spine, femur, pelvis, skull, clavicle, and
.humerus

Symptoms Continued

Other symptoms depend on which bones are

affected. Enlarged bones can pinch nerves and
cause tingling and numbness. If the disease
affects the hips or knees it can cause arthritis,
limping, and pain or stiffness of the knee or hip. If
it affects the legs, they can become bowed. If the
skull is affected it can cause headaches, and loss
of hearing and vision. If the disease is wide
spread, congestive heart failure can occur
.because of the high workload for the heart

Diagnosis and Prognosis

Paget's disease is diagnosed based on x ray appearance
as well as possible bone scans, MRI scans, or CT scans.
Also blood tests are used because an enzyme that comes
from bone, alkaline phosphatase, is usually elevated in
people who have Paget's disease because of the abnormal
.remodeling

The prognosis is generally good. The symptoms progress

slowly and the disease doesn't spread to healthy bones like
.cancer. However, there is no cure

Treatment
Since there is no cure, the goal of the treatment
is to control the disease's activity and the
complications. When there are no symptoms or
elevated levels of alkaline phosphatase, then
treatment isn't necessary. Bone pain can require
NSAIDs. Deformity can require supports.
Surgery may be necessary for damaged joints,
fractures, severely deformed bones, or when
nerves are being pinched by enlarged bone.
Medications such as bisphosphonates or
.injectable calcitonin may be used

Osteopetro
sis

Osteopetrosis, literally "stone bone", also

known as marble bone disease and
Albers-Schonberg disease is an
extremely rare inherited disorder whereby
the bones harden, becoming denser, in
contrast to more prevalent conditions like
osteoporosis, in which the bones become
less dense and more brittle, or
osteomalacia, in which the bones soften.
Osteopetrosis can cause bones to dissolve
and break

Pathogenesis
Normal bone growth is achieved by a balance between bone
formation by osteoblasts and bone resorption (breakdown of
bone matrix) by osteoclasts. In osteopetrosis, the number of
osteoclasts may be reduced, normal, or increased. Most
importantly, osteoclast dysfunction mediates the
.pathogenesis of this disease
The exact mechanism is unknown. However, deficiency of
carbonic anhydrase in osteoclasts is noted. The absence of
this enzyme causes defective hydrogen ion pumping by
osteoclasts and this in turn causes defective bone resorption
by osteoclasts, as an acidic environment is needed for
dissociation of calcium hydroxyapatite from bone matrix.
Hence, bone resorption fails while its formation persists.
.Excessive bone is formed

Symptoms
Despite this excess bone formation, people

with osteopetrosis tend to have bones that are

more brittle than normal. Mild osteopetrosis
may cause no symptoms, and present no
problems. However, serious forms can result in
stunted growth, deformity, increased likelihood
of fractures, also patients suffer anemia,
recurrent infections and hepatosplenomegaly
due to bone expansion leading to bone marrow
narrowing and extramedullary hematopoiesis.
It can also result in blindness, facial paralysis,
and deafness, due to the increased pressure
put on the nerves by the extra bone.

Differential diagnosis
The differential diagnoses include other

disorders which can cause diffuse

osteosclerosis, such as hypervitaminosis D, and
hypoparathyroidism, Paget's disease, diffuse
bone metastasis of breast or prostate cancer
(which tend to be osteoblastic while most
metastases are osteolytic), intoxication with
fluoride, lead or beryllium, and hematological
disorders such as myelofibrosis,
sickle cell disease and leukemia.

Treatment
The only durable cure for osteopetrosis types

affecting the osteoclasts (most types) is bone

marrow transplant.[5]
If complications occur in children, patients can
be treated with vitamin D. Gamma interferon
has also been shown to be effective, and it can
be associated to vitamin D. Erythropoetin has
been used to treat any associated anemia.
Corticosteroids may alleviate both the anemia
and stimulate bone resorption. Fractures and
osteomyelitis can be treated as usual.

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