Pagets Disease of Bone and Fibrous Dysplasia

Edwin M. Monsell and Geetha Subramanian

Department of Otolaryngology-Head and Neck Surgery, Wayne State University School of Medicine, Detroit, Michigan, U.S.A.

■ Introduction 308

■ Definition 308

■ Epidemiology 308

■ Pathogenesis 308

■ Clinical Manifestations 309

■ Diagnosis 309

■ Treatment 310

■ Complications and Prognosis 310

■ Fibrous Dysplasia 311

■ Introduction 311

■ Definition 311

■ Epidemiology 311

■ Pathogenesis 311

■ Clinical Manifestations 311

■ Diagnosis 312

■ Treatment 312

■ Complications and Prognosis 313

■ References 313


Paget's disease is a progressive disease of bone affecting primarily the middle aged and elderly.

The most common otolaryngic manifestation is hearing loss, which is related to involvement of the skull (1,2).


Paget's disease of bone (PDB) is a focal or multifocal disease of bone remodeling in which transformed, multinucleated osteoclasts excavate bone at a greatly accelerated rate. Cycles of osteolysis and repair continue to remodel affected bone as the lesion slowly enlarges. Pagetic bone becomes highly vascular and thicker but structurally weaker.


PDB occurs mainly in middle and later years. The disease is more prevalent in men than in women, ranging from 1.4 to 1.9:1 in various surveys. PDB is most common in North America, Europe, Australia, and New Zealand. It is more common in the United Kingdom, the Low Countries, France, and Germany and less prevalent in Scandinavia. It is relatively uncommon in Africa and Asia (3).


Evidence supports viral and genetic etiologies for PDB. Pagetic osteoclasts contain viral mRNA and inclusions that resemble paramyxoviruses. Vectors containing measles virus genes can convert osteoclast precursors to pagetic-like osteoclasts.

A positive family history of PDB has been reported in 1% to 40% of cases in various clinical series. Familial occurrence supports a dominant inheritance pattern with variable penetrance. Susceptibility loci have been mapped to chromosomes 18q21-22, 18q23, 6p21.3, and other locations. SQSTM1, a gene on chromosome 5q35 also associated with PDB, encodes a protein, p62 (sequestosome 1), which is involved in several signaling pathways important in osteoclast differentiation and activation. No single locus is associated with a large proportion of familial cases.

Normal bone undergoes continuous remodeling in an organized focal process. Osteoclasts excavate existing bone, creating a channel up to 40 to 60 mm deep within 4 to 12 days. This channel is repaired by osteoblasts in a coupled process over a period of two to three months. A feature unique to remodeling in the normal mammalian otic capsule is the sparing of a 400-|m wide zone surrounding the perilymphatic space.

Pagetic osteoclasts are larger, contain many more nuclei, and are far more active resorbers of bone than normal osteoclasts. The pattern of resorption in PDB is unrelated to the structural requirements of bone. Pagetic bone has a mosaic appearance of multiple cement lines that develop as pagetic osteoclasts and reactive osteoblasts repeatedly break down and repair areas of bone (3).

Paget's disease typically results in thickening and enlargement of the skull (Fig. 1), which expands outward, so the intracranial space is not compromised. Later, thickening

FIGURE 1 High-resolution axial computed tomography scan of the left temporal bone in a 78-year-old woman showing extensive Paget's disease of bone. The pattern of involvement shows the classic "cotton wool" appearance of Paget's disease. Audiometry showed profound deafness in this ear. Source: Courtesy of Edwin M. Monsell, MD, PhD.

and sclerosis predominate, often producing a characteristic "cotton wool" appearance on radiographs (Fig. 1).

Histologic studies in cases with pagetic hearing loss have demonstrated that hair cells and spiral ganglion cells remain intact (2). Auditory-evoked potentials are normal. The internal auditory canal lumen is not compromised. Conversely, both the sensorineural hearing loss and the air-bone gap in PDB are closely associated with the loss of bone mineral density in the cochlear capsule (1).


Paget's disease may affect any bone in the body, but it most commonly involves the skull (about 30% of cases), pelvis, long bones, and spine. Often, patients are asymptomatic, and the diagnosis is made incidentally from radiographs, bone scans, or an elevated serum alkaline phosphatase level.

PDB may present with bone pain, hearing loss, fracture, nerve root compression, or headache. Pagetic bone pain is usually constant, dull, and poorly localized. Pain may also result from osteoarthritis in the joints adjacent to the affected bones.

Hearing loss is usually bilaterally symmetrical and progressive. A high-frequency sensorineural loss and low-frequency air-bone gap are characteristics (1).


Hearing loss is one of the most common complications. Pagetic hearing loss may be suspected in any middle-aged or elderly person showing characteristic auditory features [high-frequency sensorineural hearing loss and low-frequency air-bone gap (1)] or any level of hearing loss with a positive history of PDB. Patients can be screened with a serum alkaline phosphatase test; levels of bone-specific alkaline phosphatase are often several times normal in active PDB.

Computed tomography (CT) scans are confirmatory (1). Technetium bone scans will demonstrate the areas of the skeleton that are involved. Confirmatory biopsy is rarely indicated. Radiographs may show lytic lesions that need to be differentiated from cancer metastases and other lesions. Sclerosing appearances develop later in the course of the disease.

FIGURE 1 High-resolution axial computed tomography scan of the left temporal bone in a 78-year-old woman showing extensive Paget's disease of bone. The pattern of involvement shows the classic "cotton wool" appearance of Paget's disease. Audiometry showed profound deafness in this ear. Source: Courtesy of Edwin M. Monsell, MD, PhD.


The emphasis has shifted from treatment of symptoms to treatment for prevention of complications. Lesions should be treated to prevent hearing loss, pathologic fractures, secondary arthritis, and neurologic complications. Patients should be treated before surgical procedures involving pagetic bone to reduce bleeding and risk of infection. Thus, according to current thinking, nearly every patient should be treated.

Calcitonin and etidronate were the most commonly used medications for treatment of Paget's disease in the past. These have declined in usage since the arrival of newer bisphosphonates (pamidronate, alendronate, and risedronate), which are more successful in controlling the disease with limited side effects. When the rate of bone resorption is controlled by medication, the rate of bone formation is gradually reduced. Lytic areas are at least partially repaired, and the new bone formed has a more normal lamellar appearance. Serum alkaline phosphatase levels and urinary hydroxyproline excretion approach normal values. Patients need to be followed indefinitely because the pagetic process usually resumes if treatment is discontinued (3).

Treatment may slow the progression of hearing loss but does not reverse the deficit or correct deformities of bone, even if biochemical markers are normalized. Surgical exploration, stapedotomy, and ossicular chain repair are generally not indicated because ossicular function is not impaired, even when the characteristic air-bone gap is present (1).


Involvement of the temporal bone qualitatively by CT is highly correlated with involvement of the otic capsule in quantitative CT studies, even when the otic capsule appears to be uninvolved by clinical CT.

Bilateral involvement of the otic capsules is typical when Paget's disease involves the skull. The pagetic process and associated hearing loss are established well before signs appear in the facial skeleton.

Treatment can halt the progression of the disease but does not result in improved hearing. Patients usually respond well to amplification or cochlear implantation, when indicated.

Bowing of weight-bearing bones, increased skull size, and other deformities occur in advanced disease. The maxilla and other facial bones may be involved, producing deformity. Osteosarcoma is a rare complication of the disease. It typically occurs in a setting of longstanding, widespread disease. Patients should be treated to stabilize the disease before elective surgery in affected areas to minimize intraoperative blood loss and risk of infection.


Paget's disease is a progressive disease of bone remodeling. Its systemic manifestations include bone pain and deformity. Pagetic hearing loss due to skull involvement is common and occurs before the development of obvious deformity. Treatment is usually successful in controlling the disease and reducing complications. Hearing levels are stabilized with effective treatment, but do not improve.

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