PAGET’S DISEASE (OSTEITIS

DEFORMANS)
Paget’s disease is characterized by increased bone turnover and enlargement and
thickening of the bone.
 but the internal architecture is abnormal and the bone is unusually brittle.
The condition has a curious ethnic and geographical distribution, being relatively
common :
 North America,
 Britain,
 western Europe
 Australia
 but rare in Asia,
 Africa and the
 Middle East.

There is a tendency to familial aggregation. The cause is unknown, although the

discovery of inclusion bodies in the osteoclasts has suggested a viral infection
Treatment
Most patients with Paget’s disease never have any symptoms and
require no treatment.

But

Sometimes pain is due to an associated arthritis rather than bone

disease, and this may respond to non-steroidal anti-inflammatory
therapy.
The indications for specific treatment are:
◦ (1) persistent bone pain;
◦ (2) repeated fractures;
◦ (3) neurological complications;
◦ (4) high-output cardiac failure;
◦ (5) hypercalcaemia due to immobilization; and
◦ (6) for some months before and after major bone surgery where there is a
risk of excessive haemorrhage.
Drugs that suppress bone turnover, notably calcitonin and
bisphosphonates, are most effective when the disease is active and
bone turnover is high.
Calcitonin is the most widely used.
It reduces  bone resorption by decreasing both the activity and the number
of osteoclasts; serum alkaline phosphatase and urinary hydroxyproline levels
are lowered.

Salmon calcitonin is more effective than the porcine variety;

subcutaneous injections of 50–100 MRC units are given daily until pain
is relieved and the alkaline phosphatase levels are reduced and
stabilized.
Maintenance injections once or twice weekly may have to be continued
indefinitely, but some authorities advocate stopping the drug and
resuming treatment if symptoms recur.
Bisphosphonates
Bind to hydroxyapatite crystals, inhibiting their rate of growth and
dissolution.
It is claimed that the reduction in bone turnover following their use is
associated with the formation of lamellar rather than woven bone and
that, even after treatment is stopped, there may be prolonged
remission of disease
Etidronate can be given orally (always on an empty stomach) but
dosage should be kept low (e.g. 5 mg/kg per day for up to 6 months)
and vitamin D and calcium should also be given lest impaired bone
mineralization results in osteomalacia.
The newer bisphosphonates (e.g. alendronate or pamidronate) do not
have this disadvantage, so they should be used as the treatment of
choice; they produce remissions even with short courses of 1 or 2
weeks.
Surgery
The main indication for operation is a pathological fracture, which (in a
long bone) usually requires internal fixation.
When the fracture is treated the opportunity should be taken to
straighten the bone. Other indications for surgery are painful
osteoarthritis (total joint replacement), nerve entrapment
(decompression) and severe spinal stenosis (decompression).
Beware – blood loss is likely to be excessive in these cases
ENDOCRINE DISORDERS
The endocrine system plays an important part in skeletal growth and
maturation, as well
The anterior lobe of the pituitary gland directly affects growth; it also
controls the activities of the thyroid, the gonads and the adrenal cortex,
each of which has its own influence on bone; and the pituitary itself is
subject to feedback stimuli from the other glands.as the maintenance of
bone turnover.
The various mechanisms are, in fact, part of an interactive system in
which balance is more important than individual active growth
hormone stimulates cell proliferation and growth at the physes.
Gonadal hormone promotes growth plate maturation and fusion. While
pituitary activity is in the ascendant, the bones elongate; after sexual
maturation, the rise in gonadal hormone activity simultaneously ‘feeds
back’ on the pituitary and also directly closes down further physeal
growth.
Cara minum biposphonates
Intravenous:
Zometa (zolendronic acid) 4mg-5ml/15minutes every 1 year, every 3-4
weeks oral supplement 500mg and multiple vitamin containing 400 IU
vitamin D are recommended.
 check kidney function( ureum, kreatinin, creatinine clearance)
Drink 2 glasses of water (200ml) few hour before injection, it keep from
getting dehydrated.
Side effect: may last 3-14 days.
Nausea,vomiting, diarrhea, constipation, hypotension , kidney
problems, necrotic jaw
IV regimen — Intravenous (IV) bisphosphonates (zoledronic
acid and ibandronate) provide an alternative option for patients who
cannot tolerate oral bisphosphonates or who have difficulty with dosing
requirements, including an inability to sit upright for 30 to 60
minutes and/or to swallow a pill. Zoledronic acid is administered yearly
and must be infused over a period of at least 30 minutes, whereas
ibandronate is administered every three months as a 15- to 30-second
IV injection.
Prior to receiving IV bisphosphonates, patients should be assessed for
hypocalcemia, vitamin D deficiency, and renal impairment by measuring
serum calcium, creatinine, and 25(OH)D
Oral regimen — Bisphosphonates are poorly absorbed orally (less than
1 percent of the dose) and must be taken on an empty stomach for
maximal absorption. The following regimen is recommended to
maximize absorption and minimize the risk of esophageal adverse
effects
●Bisphosphonates should not be given to patients with active upper GI
disease.
●Bisphosphonates should be discontinued in patients who develop any
symptoms of esophagitis.
●Bisphosphonates should be taken alone on an empty stomach first
thing in the morning with at least 240 mL (8 oz) of water. After
administration, the patient should not have food, drink, medications, or
supplements for at least one half-hour (alendronate, risedronate) or
one hour (ibandronate).
The regimen for enteric-coated, delayed-release risedronate is different
from that of other bisphosphonates. The enteric-coated, delayed-
release formulation is taken immediately after breakfast with 4 oz of
water. (See 'Formulations' below.)
●Patients should remain upright (sitting or standing) for at least 30
minutes after administration to minimize the risk of reflux.
Compliance is also important for optimal fracture reduction
Prior to receiving IV bisphosphonates, patients should be assessed for
hypocalcemia, vitamin D deficiency, and renal impairment by measuring
serum calcium, creatinine, and 25(OH)D
Timing of dose — Administration of bisphosphonates first thing in the
morning, prior to breakfast, appears to be important for bioavailability
and subsequent suppression of bone turnover. This was illustrated in a
randomized trial of nursing home residents who were assigned
to risedronate or placebo between meals (after a two-hour fast) for 12
weeks, rather than before breakfast or the first liquid of the day [10].
Markers of bone turnover were not suppressed as they typically would
be with before-breakfast administration, suggesting that this alternative
schedule may not provide the desired effects on BMD
Calcium/vitamin D — Vitamin D insufficiency and inadequate calcium
intake are common in patients with osteoporosis. In the majority of
bisphosphonate trials described below, calcium and vitamin D
supplements were also administered. Therefore, patients receiving
bisphosphonates should take supplemental calcium and vitamin D.
However, calcium supplements can interfere with the absorption of
bisphosphonates, and they should not be taken for at least one hour
after taking oral bisphosphonates.
Risendronate / alendronate 30 mg : 1 weeks
Risendronate / alendronate 150 mg : 1 month