Definition
Paget’s disease of bone (PDB) is a focal, chronic skeletal disorder characterized by enhanced resorption of bone as a result of overactivity of osteoclasts followed by the formation of bone by osteoblasts. This process results in a disorganized, mosaic pattern of woven and lamellar bone that is associated with increased vascularity, marrow fibrosis, and mechanical weakness. The affected bones can become enlarged, less able to resist stress, and deformed. PDB can affect one bone, termed monostotic PDB; however, it is more commonly polyostotic. The axial skeleton is primarily affected and typically includes the pelvis (72%), lumbar spine (58%), femur (55%), thoracic spine (45%), skull (42%), and tibia (35%), whereas the feet, hands, and facial bones are rarely affected.1 The most common locations for monostotic disease include the tibia and iliac bones.
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Epidemiology
It is difficult to estimate the incidence of PDB because most patients are asymptomatic. The global prevalence varies from 1.5% to 8.3% depending on factors such as age, country of residence, and sex.2, 3 Incidence increases after age 50 years.2 The prevalence is higher in the United Kingdom, France, Germany, Australia, New Zealand, and North America.2 It is rare in Asia, India, and Scandinavia. PDB is slightly more prevalent in men than in women.3
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Etiology
The exact cause of PDB is uncertain. However, available data suggest that genetic factors or viral infection, or both, might play a pathogenic role. PDB tends to aggregate in families, and between 14% and 25% of family members of patients with Paget’s disease eventually contract the disease.4, 5 First-degree relatives of patients with PDB have a 7- to 10-fold increase in risk of developing the condition.4, 5 Other studies have also suggested that a viral infection might play a role in the etiology of PDB.
The theory for a viral basis originated from a study showing that both the nuclei and cytoplasm of osteoclasts from patients with PDB contained uncharacterized viral particles not found in normal osteoclasts.6 A subsequent study using electron microscopy confirmed the presence of nuclear and cytoplasmic virus-like inclusion bodies in pagetic osteoclasts that resembled paramyxoviral nucleocapsids.7 Proteins derived from the respiratory syncytial virus and measles virus are present in pagetic osteoclasts and in cells obtained from pagetic bone cultures.8, 9 Although supported by some studies, this viral hypothesis remains controversial, but it does suggest that the development of PDB might result from a latent viral infection of osteoclasts in a genetically susceptible person.
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Clinical Presentation
Approximately 70% of patients with PDB are asymptomatic.10 The diagnosis is usually made by an incidental finding on radiograph or by routine chemistry screen showing an elevated serum alkaline phosphatase concentration. However, some patients present with a wide range of symptoms. The classic clinical manifestation of PBD is local bone pain that is usually continuous and present at rest.10 The temperature of the skin over the affected long bone or skull can be elevated, which is probably caused by increased vascularization of the surrounding tissue and bone.11 PBD can cause skeletal deformities, such as bowing of long bones, enlarged skull, pelvic alterations, and osteoarthritis if the afflicted area of bone is located in proximity to a joint. The bowing deformities, particularly in the tibia and femur, can cause gait changes and mechanical stresses.
PDB can lead to several comorbid conditions. Traumatic and pathologic fractures can occur.11 Fractures of long bones may be a serious complication, because excessive blood loss can occur as a result of the increased vascularity of pagetic bone. In less than 1% of patients with PDB, osteosarcomas can develop.2 These tumors have a poor prognosis, with a 5-year survival rate of approximately 10%.12 PDB is also associated with neurologic complications including deafness, facial nerve palsies, radiculopathies, and spinal cord compression.10 These neurologic symptoms generally result from nerve compression by enlarging bone or by interference with the blood supply. Vascular steal syndromes affecting the spinal cord and cerebral supply have been observed.10 Compression of the base of the skull, known as platybasia, can occur, leading to hydrocephalus, nerve entrapment, and cerebellar dysfunction.13 This can lead to symptoms of nausea, ataxia, incontinence, gait disturbance, or dementia.13
PDB is associated with high cardiac output, hypercalcemia, and hyperparathyroidism. High-output heart failure is rare and is a result of increased vascularization of metabolically active pagetic bone. Hypercalcemia is also rare and is normally seen in patients with severe disease who are immobile. Some studies have found an association between PDB and hyperparathyroidism, which could also account for the increase in calcium.14
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Diagnosis
As previously mentioned, asymptomatic patients with PDB are usually initially identified incidentally by radiograph or by an elevated bone-specific alkaline phosphatase obtained on routine chemistry panels.
The principal mode of diagnosis of PDB is radiographic examination of the skeleton. Plain radiographs of an affected bone reveal osteolytic, osteoblastic, or mixed lesions. Other characteristic radiologic findings include transverse lucent areas, enlargement of bones, expanding lytic changes, thickened cortices, or osteoporosis circumscripta, which refers to extensive lytic involvement in the skull.10
Although the radiograph is a powerful diagnostic tool for PDB, bone scanning is a more sensitive test in identifying pagetic lesions.15 Bone scanning detects up to 50% more lesions than can be observed on radiographs.15 Thus, bone scans are particularly useful when a patient first presents with symptoms of PDB. As soon as abnormalities are identified by bone scan, they should be confirmed by conventional radiography in at least one site of bone.15 Repeat bone scans and radiographs are not needed unless the patient has new or progressive symptoms.