• Increased osteoclast-mediated bone resorption, with subsequent compensatory increased new bone formation. 
• This results in a disorganized mosaic of woven and lamellar bone. 
• As the bone expands, it may cause deformities such as prominent frontal bossing of the skull. 
• Or it may cause pressure on vital structures such as nerve deafness. 
• The distorted architecture causes weak bone which is more subject to fracture. 
• The warmth and high output heart failure occur because the bone develops greater blood supply and more arteriovenous shunting occurs.
  
  

2. List some major complications of Paget’s disease of bone.

• Deformity, fracture, platybasia, headache, hearing abnormalities, occasional visual disturbances, bowed legs, fracture, pain, high output heart failure and osteogenic sarcoma.
  
  

3. What are the major reasons Paget’s disease of bone is treated? 

• To reduce pain, deformity, fracture or complications from any of these.
  
  

4. What are the advantages of alendronate as compared to calcitonin and etidronate for the treatment of Paget's disease?

• Calcitonin is administered by s.c. injection or nasal insuflation. 
• Calcitonin appears to have major receptor down regulation causing the so-called "escape phenomenon".
• Alendronate is more potent than calcitonin and etidronate and will cause normalization of alkaline phosphatase in about two thirds of patients. 
• Although alendronate has side effects, particularly the esophageal ulcer, there are many more persons who discontinue calcitonin because of its gastrointestinal and nasal side effects.
  
  

5. Discuss prevention of major side effects caused by alendronate.

• To increase it’s poor oral absorption, it is taken before food in the morning and without some liquids which adsorb it.
•  Food is deferred for thirty minutes after use. 
• To avoid esophagael ulcer caused by the low pH tablet sitting on the esophageal wall, the medication is taken with eight ounces of water in an upright position and patients are instructed not to lie down for thirty minutes.
•  Calcium supplements have been advised with high doses of alendronate for Paget’s disease to avoid hypocalcemia.