Paget's disease of bone

Paget's disease of bone
Name	Paget's disease of bone
Synonyms	Osteitis deformans
Caption	A skull radiograph showing characteristic changes of Paget's disease.
Field	Rheumatology, Endocrinology, Orthopedic surgery
Symptoms	Often none; bone pain, deformity, fractures, hearing loss
Complications	Osteoarthritis, Osteosarcoma, Spinal stenosis, Heart failure
Onset	Usually after age 55
Duration	Chronic
Types	Monostotic, polyostotic
Causes	Unknown; genetic and environmental factors suspected
Risks	Family history, age, European ancestry
Diagnosis	Alkaline phosphatase blood test, X-ray, Bone scan
Differential	Metastatic bone disease, Fibrous dysplasia, Osteomalacia
Treatment	Bisphosphonates, Calcitonin, Analgesics, surgery
Medication	Zoledronic acid, Alendronate, Risedronate
Prognosis	Generally good with treatment
Frequency	~1-3% of people over 55 in certain populations

Paget's disease of bone. It is a chronic disorder characterized by excessive and disorganized bone remodeling, leading to enlarged and weakened bones. The condition most commonly affects the pelvis, skull, spine, and long bones of the leg. While many individuals are asymptomatic, the disease can cause significant complications including bone pain, deformity, and an increased risk of fracture.

Signs and symptoms

Many patients are asymptomatic, with the condition discovered incidentally on X-ray or through elevated alkaline phosphatase levels. When symptomatic, the most common complaint is bone pain, which is often deep and aching. Affected bones may become enlarged, leading to noticeable deformities such as an enlarged skull or bowed tibia. Involvement of the skull can cause headache, hearing loss from compression of the cranial nerve VIII, and, rarely, hydrocephalus. In the spine, the disease can lead to spinal stenosis and nerve root compression. Increased vascularity of pagetic bone can result in high-output heart failure in severe, polyostotic cases. Pathological fractures are a significant risk, and the development of severe pain may indicate a rare complication like osteosarcoma.

Causes

The exact cause remains unknown, but it is believed to involve a combination of genetic susceptibility and environmental factors. There is a strong familial association, with mutations in the SQSTM1 gene being identified in many familial and some sporadic cases. This gene is involved in regulating osteoclast activity. Environmental factors, such as a slow viral infection (possibly with paramyxoviruses like the measles virus), have been hypothesized based on microscopic findings in osteoclasts, but this theory remains unproven. The disease is more common in people of British and European descent, suggesting a genetic predisposition within certain populations.

Diagnosis

Diagnosis often begins with the finding of an elevated serum alkaline phosphatase level, a marker of increased bone turnover. Radiographic imaging is confirmatory; X-ray findings include lytic areas, cortical thickening, trabecular coarsening, and bone enlargement. A bone scan using technetium-99m is highly sensitive for identifying the extent and activity of polyostotic disease and typically shows intense uptake in affected bones. In atypical cases, a bone biopsy may be performed to rule out other conditions like metastatic bone disease or fibrous dysplasia. Other biochemical markers, such as urinary N-telopeptide, can also be used to monitor disease activity.

Treatment

Treatment aims to control symptoms, reduce bone turnover, and prevent complications. The mainstay of pharmacological therapy is the use of potent bisphosphonates such as zoledronic acid, alendronate, or risedronate, which inhibit osteoclast-mediated bone resorption. Calcitonin, an older therapy, is now rarely used. Analgesics, including nonsteroidal anti-inflammatory drugs (NSAIDs), are used for pain management. Surgical intervention may be necessary for complications like total hip replacement for severe secondary osteoarthritis, osteotomy to correct deformity, or decompressive surgery for spinal stenosis. Patients are also advised to ensure adequate intake of calcium and vitamin D, particularly during bisphosphonate therapy.

Prognosis

The prognosis for most patients is good, especially with modern treatments that effectively suppress disease activity. Many individuals with mild, asymptomatic disease have a normal life expectancy. The primary concerns are the management of pain and the prevention of long-term complications such as fractures, deafness, and arthritis. The development of osteosarcoma, though rare (occurring in less than 1% of cases), carries a very poor prognosis. Regular monitoring with serum alkaline phosphatase and clinical assessment is recommended to guide therapy and detect complications early.

Epidemiology

Paget's disease of bone shows a striking geographic variation in prevalence. It is most common in the United Kingdom, particularly in regions like Lancashire, and is also frequently seen in other parts of Europe (e.g., France, Germany), as well as in countries with significant European migration such as the United States, Australia, and New Zealand. It is rare in Scandinavia, Asia, and Africa. Prevalence increases with age, affecting approximately 1-3% of the population over 55 in endemic areas. The incidence and severity of the disease appear to be decreasing in recent decades for unknown reasons.

Category:Musculoskeletal disorders Category:Rheumatology Category:Genetic disorders