PAGET’S DISEASE

Definition 

• A metabolic disease characterized by excessive bone destruction and repair

Epidemiology

• A common disease: 5% of the population, 10% of population >80 yrs old

Etiology

• Postulated to be related to a slow progressing viral infection of osteoclasts, possibly paramyxovirus
• Strong familial incidence

Pathophysiology

• Initiated by increased osteoclastic activity leading to increased bone resorption; osteoblastic activity increases in response to produce new bone that is structurally abnormal and fragile

Differential Diagnosis

+ Primary bone lesions

• osteogenic sarcoma
• multiple myeloma
• fibrous dysplasia

+ Secondary bone lesions

• osteitis fibrosa cystica
• metastases

Clinical Features

• usually asymptomatic (routine x-ray finding or elevated ALP)
• severe bone pain (e.g. pelvis, femur, tibia) is often the presenting complaint
• skeletal deformities – bowed tibias, kyphosis, frequent fractures
• skull involvement – headaches, increased hat size, deafness
• increased warmth over involved bones due to increased vascularity
• high output congestive heart failure

Investigations

+ Laboratory

• serum ALP is usually very high (unless burnt out)
• normal or increased serum Ca2+
• normal serum POl–
• increased urinary hydroxyproline (indicates resorption)

+ Imaging

• evaluate the extent of disease with bone scan
• initial lesion may be destructive and radiolucent
• involved bones are expanded with cortical thickening and are denser than normal
• multiple fissure fractures in long bones

Complications

+ Local

• fractures
• osteoarthritis
• cranial nerve compression and palsies, e.g. deafness
• spinal cord compression
• osteosarcoma/sarcomatous change in 1-3%
• indicated by marked bone pain, new lytic lesions and sudden increased alkaline phosphatase

+ Systemic

• hypercalcemia and nephrolithiasis
• high output congestive heart failure due to increased vascularity

Treatment

• symptomatic therapy
• treat if ALP >3x normal
• bisphosphonates, e.g. alendronate 40 mg PO OD x 6 months OR risedronate 30 mg PO OD x 3 months OR zoledronic acid 5 mg IV per yr
• calcitonin 50-100 U/d SC
• adequate calcium and vitamin D intake to prevent development of secondary hyperparathyroidism