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.
The condition presents with excess osteoclastic activity followed by a compensatory increase in osteoblastic activity, leading to the formation of disorganized bone, which is less compact, mechanically weaker, highly vascular and more susceptible to fracture. Fortunately, more than 3/4 of patients with Paget disease are asymptomatic. It is the 2nd most common bone disorder in elderly individuals, after osteoporosis. The condition can affect one or multiple bones but the axial skeleton is most often involved (spine, pelvis, and skull). The disorder does not spread to other bones. The condition does not spread to other bones but can progress in the preexisting site. A deadly complication of Paget disease is the development of pagetic sarcoma, which is fatal.
The cause of Paget disease remains unknown but there are both genetic and environmental associations. The disorder is most common in Europe, North America, and Australia but rare in Asia and Africa. A number of viruses have been identified in the diseased bone but what their role is in the disease pathology remains a mystery.
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.
A genetic predisposition to the disorder appears to be strong based on population studies. Besides finding an association between HLA markers, siblings are at high risk for developing the disorder.
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. In the US, it is said to affect 1-3 million people but most are asymptomatic. The disorder is slightly more common in white males. The disorder usually presents in the 4-5 decade of life but the diagnosis is often made a decade later.
Paget disease occurs when there's an increase in 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 their 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 the osteoblastic activity is observed and culminates in the final stage, where malignant degeneration will be seen.
The disease occurs in isolated pockets but is usually progressive. Often there is erythema and warmth over the involved bone due to hypervascularity, which in turn can also lead to high output heart failure.
The disease can affect almost every bone in the skeleton but has an affinity for the long bones, axial skeleton, and skull. The involvement of the feet and hands is very rare.
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 the clinic with pathognomonic features associated with Paget disease are usually asymptomatic. The majority of patients with the condition are often diagnosed by an incidental finding on an x-ray study. The disease will present with one bone affected in 1/3rd of cases. The spine and pelvis are commonly affected and among the long bones, the femur is often involved. Symptomatic patients can present with the following:
The lumbar spine, sacrum, and skull are involved in most cases. Pain is a common feature and is worse with weight-bearing.
The physical exam may show bone deformity or angulation, localized pain to palpation and increased warmth. The gait may be altered and there may be balance problems.
Incomplete fractures are common in Paget disease and seen in the tibia and femur. Even mild injuries can result in fractures. Femur fractures often involve the subtrochanteric region.
Osteosarcoma is a rare complication but should be suspected in a patient with sudden increase in swelling or bone pain. The disorder is fatal. Giant cell tumors may also arise in paget bone and involve the facial bones. With vertebral fractures, acute spinal cord compression can occur.
An increase in cardiac output is noted in 20% of patients when the axial skeleton is involved. In addition, calcified aortic stenosis is also common in this population.
Tests to assist in the diagnosis of Paget disease include:
This disease also may affect the results of the following:
Measurement of serum alkaline phosphatase is useful as well as urine levels of hydroxyproline, C-telopeptide, and N telopeptide.
Procollagen N terminal peptide is also a sensitive serum marker for bone formation.
Hyperuricemia is common and is due to a high turnover of bone.
Secondary hyperparathyroidism occurs in about 10% of patients due to inadequate calcium in the face of increased demand.
Plain x-rays may reveal arthritis, fractures of gross bony lesions.
Bone scans can help document the extent of disease and can be used to follow treatment. In addition, a bone scan can pick up early changes in bone even before the patient develops symptoms.
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 are usually offered as an option to patients diagnosed with Paget disease when there is a progression into osteosarcoma. The 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 a 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.
Patients with cauda equina and other nerve compression complications often require laminotomy.
The differential diagnosis includes:
The prognosis for patients who are treated is good, especially if the disease is in its early stages. There is no cure for Paget disease but the disorder can be controlled from progressing. Patients with polyostotic disease tend to have poor outcomes compared to monostotic disease. The morbidity is usually due to fractures, chronic pain, bone deformity, and neurological complications. Once the patient develops sarcomatous degeneration, the survival rate is very poor.
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:
Paget disease is the second most common bone disorder in the elderly and is associated with very high morbidity and mortality. There is no cure for the disorder and early diagnosis is key.
The diagnosis and management of Paget disease are with an interprofessional team that consists of a rheumatologist, neurologist, audiologist, internist, nurse practitioner, and a pathologist. Asymptomatic patients do not require treatment.
Patients need to be referred to a physical therapist as they need to learn about body mechanics, proper posture and avoidance of trauma. Because the patients have weak bones, patients need to be educated about protected weight-bearing and the use of ambulatory devices. The nurse should reinforce education about safe ambulation to prevent fractures. Immobility should be avoided as it also increases morbidity. The pharmacist should educate the patient on medication compliance and potential adverse effects, and nursing should watch for signs of adverse drug effects and monitor treatment progress on subsequent visits, reporting any findings to the clinician staff.
Symptomatic patients usually can be managed by bisphosphonates, calcitonin and vitamin D supplements. The pharmacist should be involved in agent and dosing decisions to optimize the therapeutic effect. A pain specialist should be involved as these patients have moderate to severe bony pain that is often disabling.
Indications for surgery are usually offered as an option to patients diagnosed with Paget disease when there is a progression into osteosarcoma. The majority of patients diagnosed with osteosarcoma are often offered palliative options such as amputation of the affected limb. 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.
These examples of interprofessional teamwork demonstrate how such collaboration between disciplines can result in optimal patient outcomes. [Level 5]
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