Pathology
Paget’s disease (PD) or
osteitis deformans is a bone remodeling disease that affects
primarily persons over the age of forty. It is most commonly
diagnosed in the sixth decade but can affect any age group
(juvenile/infantile PD). Prevalence increases with age. In fact it
is the second most common bone disorder after osteoporosis in the
geriatric population. PD affects approximately 3% of the US
population of English decent and older than 55 years of age. Men are
affected slightly more than women. The disease appears to be much
less prevalent in persons of African and Asian descent. In Great
Britain an incidence as high as 9% has been sited. Varying incidence
rates between geographic areas suggests that there may be
environmental factors contributing to the etiology of the disease,
however, the etiology still remains unknown. With respect to the
etiology, viral nuclear inclusions (both canine distemper and
paramyxovirus, measles in particular) have been detected in
osteoclasts suggesting that there may be a viral origin. There is
some data to suggest that there may also be a genetic component to
the etiology.
The disease can be divided into three phases of increasing clinical
and radiographic severity: 1) initial resorptive/osteolytic phase,
2) mid-phase, mixed, osteoblastic/osteoclastic hyperplasia and 3)
late sclerotic phase. The most common sites that are affected
include the pelvis, spine, femur and skull. Moreover, the tibia,
humerus, scapula and clavicle are not as commonly involved. The
disease can be polystotic or monostotic.
The initial phase is
characterized by increased osteoclastic activity that produces a
radiologic picture of advancing, metaphyseal to diaphyseal V-shaped
cutting zone in long bones on plain X-ray. In addition, the skull
can express a skullcap shaped area of resorption that is
pathognomonic for PD (osteoporosis circumscripta). These areas of
increased bone remodeling can be detected with up to 30% increased
sensitivity by scintigraphy versus plain film. The differentiation
between blastic metastasis and PD is difficult. This distinction can
be elucidated using pinhole scintigraphy to visualize uptake
distribution (PD has evenly distributed cortical uptake). Moreover,
scintigraphy is very effective at detecting all affected bones and
thus evaluating extent of disease. Clinically the initial phase has
an insidious onset including pain and possibly fractures. In 90% of
cases the initial phase is asymptomatic with incidental diagnosis.
The second/mixed phase
consists mostly of increased osteoblastic activity in response to
initial phase osteoclast activity. The majority of patients present
in this stage of the disease. The resorptive process does not stop
but continues in pulses that are then countered by osteoblastic
repair. Overall osteoblastic activity eventually pervades. This type
of activity produces a framework of bone that is considerably weaker
than disease-free remodeled bone. In plain X-ray the four features
of cutting cones proximally, coarsening of trabeculae along stress
lines, widening of bone and cortical thickening predominate. The
lesions in the skull begin to take on a "cotton-wool" appearance.
Laboratory findings include elevated serum alkaline phosphatase and
elevation of urinary hydroxyproline.
The late phase is
characterized by diminished osteoclast and osteoblast activity.
Radiographically there are blastic to mixed blastic-lytic lesions
that are encapsulated by new bone growth. Clinically the patients in
this late phase have severe disease. Morbidity is at its highest
encompassing fractures (banana), high output cardiac failure,
deafness and blindness due to cranial nerve compression and
malformation of the inner ear bones, acceleration of degenerative
joint disease and development of crystal deposition disease. Also
mandibular deformation, spinal kyphosis, and long bone bowing are
prevalent. 1% of all individuals inflicted with PD and 10% of
patients in late stage of PD go on to malignant transformation with
extremely high mortality.
Prognosis
The outlook is generally good, particularly if treatment is
given before major changes in the affected bones have occurred. Any
bone or bones can be affected, but Paget's disease occurs most
frequently in the spine, skull, pelvis, thighs, and lower legs. In
general, symptoms progress slowly, and the disease does not spread
to normal bones. Treatment can control Paget's disease and lessen
symptoms but is not a cure. Osteogenic sarcoma, a form of bone
cancer, is an extremely rare complication that occurs in less than
one percent of all patients.
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Treatment:
The treatment is generaly syptomaticSurgery may
be recommended for
Fractures -- Surgery may allow fractures to heal in
better position.
Severe degenerative arthritis -- If disability is
severe and medication and physical therapy are no longer helpful,
joint replacement of the hips and knees may be considered.
Bone deformity -- Cutting and realignment of
Pagetic bone (osteotomy) may help painful weight-bearing joints,
especially the knees.
Complications resulting from enlargement of the
skull or spine may injure the nervous system. However, most
neurologic symptoms, even those that are moderately severe, can be
treated with medication and do not require neurosurgery.
Drug therapy
The goal of treatment is to control Paget's disease activity for as
long a period of time as possible.
Bisphosphonates. Five bisphosphonates are currently
available. As a rule, bisphosphonate tablets should be taken with
6-8 oz of tap water on an empty stomach. None of these drugs should
be used by people with severe kidney disease.
Didronel® (etidronate disodium) -- Tablet; approved
regimen is 200-400 mg once daily for 6 months; the higher dose (400
mg) is more commonly used; no food, beverages, or medications for 2
hours before and after taking; course should not exceed 6 months,
but repeat courses can be given after rest periods, preferably of
3-6 months duration.
Aredia® (pamidronate disodium) -- Intravenous;
approved regimen 30 mg infusion over 4 hours on 3 consecutive days;
more commonly used regimen 60 mg over 2-4 hours for 2 or more
consecutive or non-consecutive days.
Fosamax® (alendronate sodium) -- Tablet; 40 mg once
daily for 6 months; patients should wait at least 30 minutes after
taking before eating any food, drinking anything other than tap
water, taking any medication, or lying down (patient may sit).
Skelid® (tiludronate disodium) -- Tablet; 400 mg
(two 200 mg tablets) once daily for 3 months; may be taken any time
of day, as long as there is a period of 2 hours before and after
resuming food, beverages, and medications.
Actonel® (risedronate sodium) -- Tablet; 30 mg once
daily for 2 months; patients should wait at least 30 minutes after
taking before eating any food, drinking anything other than tap
water, taking any medication, or lying down (patient may sit).
Calcitonin
Miacalcin® is administered by injection; 50 to 100 units
daily or 3 times per week for 6-18 months.
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