Paget's disease

Paget's disease of bone (syn. morbus Paget, osteitis deformans, osteodystrophia deformans) is a disease characterized by bone remodeling defect with localized excessive bone resorption, compensated by increased neoplasia of structurally incomplete bone. The newly formed bone is chaotically disorganized, thus it is referred as "felt bone". The disorganized bones are more prone to fracture.

The disease affects either: Axial skeleton is typically affected: spine, pelvis, femur, sacrum, skull.
 * 1) single bone – monostotic form (15 %),
 * 2) multiple bones – polyostotic form.

Epidemiology
Paget's disease is common in Europe (United Kingdom), North America, Australia, New Zealand. It is rather uncommon in Asia and Africa.

Symptoms of Paget's disease starts to occur in 5-6th decade of life for both men and women (gender ratio men:women = 3:2)

Etiology
The underlying causes are yet to be known, though the involvement of genetic factors and viral infections (environmental factors) is suggested.

Pathogenesis

 * 1) Osteoclastic phase: characterized by increased activity of abnormal osteoclasts (with several times more nuclei than normal osteoclasts)
 * 2) Mixed phase: increased osteolysis leads to increased osteogenesis.
 * 3) Sclerotic phase: osteogenesis dominates

Symptoms
70–80 % of patients are asymptomatic.

In symptomatic cases:


 * Bone pain (ostalgia, osteodynia) and pain in adjacent joints. The pain is localized and dull, usually occurs at night,
 * Deformity of bones, skulls, enlargement and deformities of vertebrae,
 * Headache,
 * Increased head circumference (patients cannot fit a hat they usually wear),
 * Compression of nerves in inner ear by narrowed auditory foramen (hearing loss)
 * Numerous arteriovenous connections in the area of newly formed bone, which leads to an increased blood flow, causing increased temperature above the affected area when palpated.
 * bone fractures

Differential Diagnosis

 * Osteomalacia,
 * Osteoporosis,
 * Osteoarthritis,
 * Bone metastases,
 * Primary bone tumor,
 * Hyperparathyroidism.

Diagnostics
Patient's history: In 14% of the cases, the disease is seen in family.

Imaging techniques: X-ray (osteolytic and sclerotic lesions), CT, radioisotope bone scan

Laboratory diagnostics (markers of bone remodelling):
 * Markers of bone resorption: deoxypyridinoline, N-telopeptide and C-telopeptide collagen I (INTP, ICTP),
 * Markers of osteogenesis: ALP (bone isoenzymes)
 * Serum values of calcium, phosphorus, and PTH: can be within a normal range

Complications

 * Bone: fractures,deformities, bone sarcoma
 * Nervous system: compression of anterior and posterior spinal nerve roots, deafness
 * Increased bone perfusion can lead to hypercirculation, which can cause a heart failure in some severe cases.

Treatment

 * Biophosphonates (alendronate, pamidronate, zoledronate, etc.),
 * Analogues of calcitonin,
 * Non-steroidal anti-inflammatory agents (NSPZL),
 * Supplementation of vitamin D and calcium,


 * Surgical therapy of bone deformities, and/or fractures,
 * Regular check-ups.

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