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.
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.
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.
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.
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.
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.
Tests to assist in the diagnosis of Paget disease include:
This disease also may affect the results of the following:
Some patients diagnosed with Paget disease may not require treatment. This patient cohort includes:
The most commonly treated patients diagnosed with Paget disease include:
There are several treatment regimens that aid in prophylactically preventing bone breakdown and the subsequent formation. Some of the more common drug therapies include:
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.
The differential diagnosis includes:
Diet and Activity
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.
Current endocrine guidelines for Paget disease: