Paget Disease

Article Author:
Philip Bouchette
Article Editor:
Sameh Boktor
Updated:
10/27/2018 12:31:46 PM
PubMed Link:
Paget Disease

Introduction

Paget disease is a skeletal growth disorder in which abnormalities such as unusual bone growth can occur in several multifactoral ways. This is often manifested by diffuse pain throughout the musculoskeletal system.

Etiology

Some literary sources suggest that the family of paramyxoviruses solely causes Paget. However, many studies have come to determine that the osteoclast generation of a unique cytokine found exclusively in the bone marrow of patients diagnosed with Paget disease may be the primary insult. This cytokine is known as IL-6.

Epidemiology

Paget disease is usually seen in individuals older than 50 years. It is common in Caucasians of northern European descent. Paget disease is equally common in males and females.

Pathophysiology

Paget disease occurs when there's an increase of bone resorption that leads to a decrease in bone mass and lytic structures. This process gives rise to osteoblasts from the bone utilizing a sensing system that allows them to increase its activity.

Paget disease pathological process occurs in four stages. Briefly, it begins with osteoclastic activity followed by a hybrid osteoclastic/osteoblastic process. The third stage is where osteoblastic activity is observed and culminates in the final stage, where malignant degeneration will be seen.

Histopathology

The key histopathological features of Paget disease involve the bone architecture and includes the three phases of the disease: mixed, osteolytic, and osteosclerotic. These phases may occur at the same time or separately. The osteolytic phase has areas of resorption due to a large increase in the number of abnormal osteoclasts that contain dozens of nuclei. The osteoblastic phase that follows is disorganized. The bone development is fragmented and irregular. The presence of irregularly shaped bone particles appear like a jigsaw and are a hallmark feature of  Paget disease. As the disorder advances, the osteoblastic phase becomes dominant, resulting in excessive bone formation which is fibrous and coarse. The marrow space is filled with vascularized fibrous tissue, which accounts for the persistence warmth and fever.

The bone in Paget disease does not have centralized blood vessels or Haversian systems. Once the osteoblastic phase subsides, the new bone is poorly mineralized and is devoid of any structural integrity.

History and Physical

Many patients that present to clinic with pathognomonic features associated with Paget disease are usually symptomatic. Majority of patients with the condition are often diagnosed by an incidental finding on an x-ray study.

Examples include:

  • Pain involving the bones and joints
  • Diffuse joint stiffness
  • Abnormally enlarged skull
  • Musculoskeletal deformities
  • Loss of hearing
  • Migraines
  • Fractures

Evaluation

Tests to assist in the diagnosis of Paget disease include:

  • Bone scan
  • Bone x-ray
  • Elevated markers of bone breakdown like N-telopeptide

 This disease also may affect the results of the following: 

  • Elevated ALP (alkaline phosphatase) 
  • Normal Serum calcium and Phosphate

Treatment / Management

Some patients diagnosed with Paget disease may not require treatment.  This patient cohort includes:

  • Patients with abnormal blood test
  • Patients who have no active signs of the disease and those who are asymptomatic

The most commonly treated patients diagnosed with Paget disease include:

  • Those with abnormal bone defects
  • When weight-bearing bones are involved
  • Those with skull deformities
  • When there’s evidence of a rapidly progressing bone changes
  • Patients with complaints of diffuse pain

There are several treatment regimens that aid in prophylactically preventing bone breakdown and the subsequent formation.  Some of the more common drug therapies include:

  • Bisphosphonates, which has been proven as the first-line treatment option, secondary to its influence in bone remodeling.
  • Calcitonin is usually second-line treatment. This drug is assisted in bone absorption
  • Supplements such as calcium and vitamin D have been known to provide some symptomatic benefit
  • Pain management achieved with either NSAIDs or acetaminophen

Indications for surgery is usually offered as an option to patients diagnosed with Paget disease when there is a progression into osteosarcoma. Majority of patients diagnosed with osteosarcoma are often offered palliative options such as amputation of the affected limb. In many cases, clinicians are often tasked with the job of making judgment calls about which treatment options to offer the wide spectrum of patients that may be diagnosed. For example, younger patients are usually offered surgical procedure where they could potentially salvage the limb by resecting the tumor with wide margins. This may not be a viable alternative for an elderly patient with multiple comorbidities and risk factors. Patients may also develop pathological fractures that may need radiation and internal fixation to relieve pain burden. Chemotherapy has been shown to be an ineffective option for patients diagnosed with a sarcoma. It is important to note that surgical failure rates are high in this group of patients. Often, revision surgery is indicated.

Differential Diagnosis

The differential diagnosis includes:

  • Osteomalacia
  • Osteoporosis
  • Malignancy
  • Renal osteodystrophy
  • Osteoarthritis
  • Osteopenia
  • Fibrous dysplasia

Pearls and Other Issues

Diet and Activity

  • While there is no specific diet for patients with Paget disease, those who are prescribed bisphosphonates should ensure adequate intake of calcium and vitamin D.
  • Aggressive physical activity is not recommended, as the risk of fractures is high. However, muscle strengthening exercise at a low level is recommended

Deterrence

To date, there is no way to prevent Paget disease since the cause remains unknown. For family members of a patient with Paget disease, some physicians do recommend monitoring levels of alkaline phosphatase levels every 2 years. If the levels are within the normal range, then imaging of the bone may also be performed.

Guidelines Summary

Current endocrine guidelines for Paget disease:

  • Obtain plain x-rays of the affected body part
  • Determine extent of bone involvement with a radionuclide scan
  • Measure levels of serum alkaline phosphatase to assess bone formation/resorption to assess response to treatment or follow untreated patients
  • Patients at risk for complications like fracture should be started on bisphosphonates
  • Another option is a single 5 mg dose of intravenous zoledronate if there are no contraindications
  • If a patient has normal alkaline phosphatase levels, monitor disease with a specific marker for bone formation
  • One can follow patients with serial bone scans to assess disease of bone markers are all normal
  • Use of bisphosphonates is effective in slowing progress of disease or hearing loss
  • If patients with Paget disease need surgery, consider pre-treatment with bisphosphonates.