Paget Disease of Bone

Key Features

Essentials of Diagnosis

• Often asymptomatic

• Bone pain may be first symptom

• Kyphosis, bowed tibias, large head, deafness

• Frequent fractures

• Serum calcium and phosphate normal; elevated alkaline phosphatase and urinary hydroxyproline

• Dense, expanded bones on radiograph

General Considerations

• Common condition manifested by one or more bony lesions having high bone turnover and disorganized osteoid formation

• Involved bones

  • Have increased osteoclast activity, causing lytic lesions in bone that may progress at about 1 cm/yr

  • Increased osteoblastic activity follows, producing a high rate of disorganized bone formation

  • Become vascular, weak, and deformed

  • Eventually, there appears to be a final burned-out phase with markedly reduced bone cell activity and abnormal bones that may be enlarged with skeletal deformity

• Most often discovered incidentally during radiographic imaging or evaluation of serum alkaline phosphatase elevation

• Cause is unknown; about 20% of cases are familial and transmitted as an autosomal dominant trait with incomplete penetrance

Demographics

• Most common in the United Kingdom and in areas of European migration

• Rare in Africa, India, Asia, and Scandinavia

• In the United States, Paget disease is usually diagnosed in patients over age 40 years

• Affects about 1% of whites over age 55 years; prevalence increasing with age

Clinical Findings

Symptoms and Signs

• Often mild and asymptomatic; only 27% symptomatic at diagnosis

• Involves multiple bones (polyostotic) in 72% and only a single bone (monostotic) in 28%, occurring most commonly in the pelvis, vertebrae, femur, humerus, and skull

• Pain is usual first symptom

  • Usually described as aching and deep

  • Often worse at night

• Bones become soft, leading to bowed tibias, kyphosis, and frequent fractures with slight trauma

• If skull is involved, patient may report headaches, increased hat size, and deafness

• Increased vascularity over involved bones causes increased warmth

• Sarcomatous change suggested by marked increase in bone pain

Differential Diagnosis

• Bone tumor, eg, osteosarcoma

• Plasma cell myeloma (formerly multiple myeloma)

• Metastatic cancer

• Fibrous dysplasia

• Osteitis fibrosa cystica

• Fibrogenesis imperfecta ossium

• Myelofibrosis

• Intramedullary osteosclerosis

• Erdheim-Chester disease

• Langerhans cell histiocytosis

• Sickle cell disease

Diagnosis

Laboratory Tests

• Serum alkaline phosphatase markedly elevated

• Other markers of bone turnover are also usually elevated, particularly

  • Serum procollagen type-I N-terminal propeptide (PINP)

  • Urine N-telopeptide of type 1I collagen cross-links (NTx)

• Serum calcium may be elevated, particularly if patient is at bed rest

• A serum 25-OH vitamin D should be obtained to screen for vitamin D deficiency, which

  • Can present with an increased serum alkaline phosphatase and bone pain

  • Should be corrected before prescribing a bisphosphonate

• Sarcomatous change is suggested by sudden rise in serum alkaline phosphatase

Imaging ...