Endocrinology Made Simple : Paget”s Disease

Paget”s Disease:

Definition

Paget disease is a  disorder of bone remodelling characterized by excessive bone resorption followed by an increase in bone formation.

Etiology:

Some studies suggest a genetic linkage for Paget disease located on chromosome arm 18q.

Although the etiology of Paget disease is unknown, both genetic and environmental contributors have been suggested. Ethnic and geographic clustering of Paget disease is well described.

Pathophysiology:

There is  osteoclastic overactivity followed by compensatory osteoblastic activity leads to a structurally disorganized mosaic of bone (woven bone), which is mechanically weaker, larger, less compact, more vascular, and more susceptible to fracture than normal adult lamellar bone.

Clinical Features:

Approximately 70-90% of persons with Paget disease are asymptomatic; however, a minority of affected individuals experience various symptoms, including the following:

 Bone pain (the most common symptom)

 Secondary osteoarthritis (when Paget disease occurs around a joint)

 Bony deformity (most commonly bowing of an extremity)

 Excessive warmth (due to hypervascularity)

 Neurologic complications (caused by the compression of neural tissues)

Sites of involvement:

Paget disease may involve a single bone but is more frequently multifocal. It has a predilection for the axial skeleton (ie, spine, pelvis, femur, sacrum, and skull, in descending order of frequency), but any bone may be affected.

After onset, Paget disease does not spread from bone to bone, but it may become progressively worse at pre-existing sites.

Indications for Treatment :

Intolerable pain

Involvement of weight bearing joints

Neurological involvement

Hypercalcemia

Hypercalcinuria

Congestive Cardiac Failure

Management Guidelines:

Several bisphosphonates : Alendronate,Risedronate and Pamidronate are approved for treatment of Pagets”s Disease.

Six months of treatment with oral alendronate and two months of treatment with oral risedronate lead to sustained remission in a large number of patients.

Intravenous pamidronate canbe used for patients with contraindications to use of oral bisphosphonates.

A 2014 Endocrine Society Clinical Practice Guideline on Paget disease recommends the following : 

Plain radiographs of the pertinent regions of the skeleton in patients with suspected Paget disease

A radionucleotide bone scan to determine the extent of the disease if the diagnosis is confirmed

Measurement of serum total alkaline phosphatase or, when warranted, a more specific marker of bone

formation or bone resorption to assess the response to treatment or evolution of the disease in untreated patients 

Consider treatment with a bisphosphonate for most patients with active Paget disease who are at risk for future complications

Consider a single 5-mg dose of intravenous zoledronate as the treatment of choice in patients who have no contraindication

Consider measurement of a specific marker of bone formation and bone resorption in patients with monostotic disease who have a normal serum total alkaline phosphatase

Consider serial radionuclide bone scans to determine the response to treatment if the markers are normal

Bisphosphonate treatment may be effective in preventing or slowing the progress of hearing loss and osteoarthritis in joints adjacent to Paget disease and may reverse paraplegia associated with spinal Paget disease

Consider treatment with a bisphosphonate before surgery on pagetic bone