AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Differentials
• Radiograph
• CT SCAN
• MRI
• Nuclear Medicine
• Intervention
• Multimedia
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Differentials
• Radiograph
• CT SCAN
• MRI
• Nuclear Medicine
• Intervention
• Multimedia
• References

Background

Paget disease of the bone (osteitis deformans) is a metabolic disorder characterized by abnormal osseous remodeling. Sir James Paget first described Paget disease in 1877 as a chronic inflammatory remodeling disease of bones. He termed the condition osteitis deformans.¹

(See also the eMedicine articles Bone Metastases and  Paget Disease [in Rheumatology], as well as Novel approach to Paget's disease: Targeting osteoclastogenesis, on Medscape.)

Pathophysiology

The etiology of Paget disease is uncertain, but it may be caused by a viral infection, possibly of the Paramyxoviridae family.² Genetic predisposition to the development of Paget disease may exist as well. Clustering within families has been reported, supporting this theory. In addition, regional differences in disease prevalence support a significant environmental influence.^{3, 4, 5}

Paget disease evolves through 3 stages as follows:

• An early lytic or hot phase
• An intermediate or mixed phase
• A final or cold phase, marked by dense bone formation

Paget disease rarely is diagnosed in the initial lytic phase. At this early point of the disease, osteoclastic activity is predominant. Paget disease usually begins at the end of a bone, except when it occurs in the tibia. A characteristic sharply demarcated zone of osteolysis may begin in the subcortical bone and advance along the diaphysis. Osteoblastic activity lags behind; thus, radiolucent fibrous tissue replaces normal bone.

The intermediate or mixed phase reveals evidence of osteolytic and disorganized osteoblastic activity. New bone forms abnormally and demonstrates characteristically coarsened trabecula and cortical thickening in the cancellous and compact bone, respectively. Characteristic intracytoplasmic inclusions may be observed microscopically, supporting evidence for the viral etiology theory.

The final or cold phase demonstrates less evidence of continual osseous remodeling. Previously laid down woven bone is converted to dense lamellar bone. Histologic features of disorganized bone are prominent. The intersecting lines of remodeled bone have a characteristic mosaic pattern histologically (see Image 1).

Frequency

United States

Paget disease occurs more commonly in the northern regions than in the southern regions, supporting the role of environmental influence in Paget disease. Paget disease affects 3-4% of the general population older than 40 years in the US.⁶

International

Paget disease may be found in more than 10% of the population older than 85 years. Paget disease is common in England and throughout Europe, except Scandinavia, and in New Zealand, Australia, and North America. Paget disease is rare in Asia and most of Africa, excluding South Africa (with its European immigrant population).^{7, 8, 9}

Mortality/Morbidity

Patients usually are asymptomatic, although the most frequent symptom is pain. Complications include insufficiency and pathologic fractures, secondary arthritis, nerve impingement in the spine or skull base, and, rarely, sarcomatous degeneration of the pagetic bone. ¹⁰

Development of secondary sarcoma in pagetic bone is the most lethal complication, occurring in 1% or fewer of patients with Paget disease (see Image 2). These sarcomas are aggressive and may be multicentric. The 5-year survival rate is almost zero. Histology most frequently demonstrates osteosarcoma, with malignant fibrous histiocytoma accounting for most of the remaining tumors.^{11, 12, 13}

Chemotherapeutic regimens are relatively ineffective and often quite toxic, particularly since there is a high likelihood of concurrent disease in these patients, who are typically older persons. Surgical intervention often is palliative at best. However, if diagnosed in the appendicular skeleton before metastases are present, surgical treatment may improve the chance of survival. Pagetic sarcoma may present with pain or pathologic fracture. Alkaline phosphatase levels may increase but occasionally remain normal.^{14, 10}

Multiple giant cell tumors rarely are observed in association with Paget disease. The usual sites of involvement are the skull and facial bones. These lesions often respond well to steroid therapy.¹⁵

Race

Paget disease is more common in black Americans than in black Africans and is rare in Asians.

Sex

The male-to-female ratio is approximately 1.8:1.

Age

Paget disease typically is seen in older individuals and is uncommon before age 45 years. Onset of disease may occur earlier in men than in women.

Anatomy

Paget disease may be monostotic but more commonly is polyostotic. The bones most frequently affected are the pelvis, calvaria, lumbar and thoracic spine, femur, tibia, and humerus.

Clinical Details

Most patients with Paget disease are asymptomatic, and the disease is discovered incidentally. However, patients may develop a variety of signs and symptoms, depending on the site and severity of involvement.^{16, 14}

The most frequent complaint is pain, most commonly in the back and hip, followed by pain in the long bones and pelvis. Weight bearing may exacerbate pain in the spine, pelvis, or lower extremity. Disease in the skull may be accompanied by headache. Deafness also may occur from cranial nerve compression or middle-ear ossicle involvement. Pain may be present from secondary arthritis or nerve compression. Secondary arthritis most often affects the hips, knees, and ankles. Lower extremity limb shortening may be secondary to bowing of the tibia and femur.

Insufficiency fractures may present with pain that can last up to several weeks. If pain is focal and severe, it may be a sign of an impending, complete fracture, and radiographic evaluation is warranted. Insufficiency fractures most frequently affect the femur and tibia.

Consider medical treatment when a biochemically active disease may lead to complications or when significant disease is found in high-risk sites such as the proximal femur (see Image 3). Involvement in such a critical weight-bearing location may lead to fracture (see Image 4) or severe secondary arthritis. In addition, consider treatment in the presence of severe symptoms, such as bone pain or nerve compression, and prior to orthopedic surgical intervention within pagetic bone. Typical treatment regimens include analgesic and antiresorptive medications such as bisphosphonates.^{17, 10}

Preferred Examination

The radiographic findings of Paget disease are diagnostic in many patients. The lytic stage most commonly is observed in the skull and long bones. The typical appearance in the long bones is osteolysis, which begins in the epiphysis and advances along the diaphysis. Trabecular coarsening and distortion and cortical thickening are observed in the sclerotic phase, typically involving the axial skeleton.

Limitations of Techniques

Radiographic findings in Paget disease often are pathognomonic, particularly in the lytic phase. However, given the variable imaging appearance of Paget disease in different stages, as well as the many different bones involved, the differential diagnosis may vary substantially among patients.

DIFFERENTIALS

Section 3 of 10  

• Authors and Editors
• Introduction
• Differentials
• Radiograph
• CT SCAN
• MRI
• Nuclear Medicine
• Intervention
• Multimedia
• References

Other Problems to be Considered

Bony sclerosis without osseous enlargement, including blastic metastases, myelofibrosis, renal osteodystrophy, fibrous dysplasia, fluorosis, mastocytosis, and tuberous sclerosis

Coarsened trabecula in the axial skeleton with osteomalacia

Calvarial hyperostosis with hyperostosis frontalis interna, fibrous dysplasia, anemia, and metastatic disease

Hyperphosphatasia (juvenile Paget disease) in young patients

RADIOGRAPH

Section 4 of 10  

• Authors and Editors
• Introduction
• Differentials
• Radiograph
• CT SCAN
• MRI
• Nuclear Medicine
• Intervention
• Multimedia
• References

Findings

Characteristic radiographic findings include the following:

• In the skull, the lytic phase (osteoporosis circumscripta) typically involves the frontal or occipital bones (see Image 5) and progresses to a mixed pattern with multifocal sclerotic patches in the intermediate stage of the disease, referred to as a cotton wool appearance (see Image 6).
• The vertebral bodies typically become enlarged (see Image 7) with a prominent cortical margin (picture frame vertebrae) or become densely sclerotic (see Image 8), mimicking lymphoma or metastatic disease (ivory vertebra).
• In the pelvis, typical findings include thickening of the iliopectineal line in early stages, progressing to patchy sclerosis and lucency in later stages (see Image 9).
• Weakening of the pagetic acetabular bone may lead to protrusio acetabuli and insufficiency fracture (see Image 10).
• In the long bones, early involvement consists of lysis of the subarticular bone, which advances along the diaphysis with the characteristic shape of a blade of grass (see Image 11). Long bones are affected first in the epiphyseal region, with the exception of the tibia, where Paget disease frequently begins in the tubercle (see Image 12). Later stages of disease show development of enlarged, sclerotic, deformed bones with thickened coarse trabeculae (see Image 13). The weakened femur and tibia eventually may become bowed under the stress of weight bearing. Insufficiency fractures may occur, characteristically involving the convex cortical surface (see Image 14). Conversely, Looser zones of osteomalacia typically occur on the concave cortical surface.

CT SCAN

Section 5 of 10  

• Authors and Editors
• Introduction
• Differentials
• Radiograph
• CT SCAN
• MRI
• Nuclear Medicine
• Intervention
• Multimedia
• References

Findings

Cross-sectional MRI and CT demonstrate enlarged bones with trabecular coarsening and increased cortical thickness (see Images 15-16). The anatomy is well demonstrated by cross-sectional imaging in complex structures, such as the spine, where spinal or nerve root compression may be an issue (see Image 17). Cross-sectional imaging also helps delineate the pathology in complicated Paget disease, which includes nerve or spinal cord compression, as well as basilar invagination at the skull base and osseous encroachment involving cranial nerve foramina. Secondary sarcomatous development also is better evaluated with cross-sectional imaging. Additionally, should biopsy be indicated for the diagnosis of sarcoma, CT typically is the guidance modality of choice.

MRI

Section 6 of 10  

• Authors and Editors
• Introduction
• Differentials
• Radiograph
• CT SCAN
• MRI
• Nuclear Medicine
• Intervention
• Multimedia
• References

Findings

See CT Scan section.

NUCLEAR MEDICINE

Section 7 of 10  

• Authors and Editors
• Introduction
• Differentials
• Radiograph
• CT SCAN
• MRI
• Nuclear Medicine
• Intervention
• Multimedia
• References

Findings

Skeletal scintigraphy is useful. Radionuclide bone scans are more sensitive than radiographs for the diagnosis of Paget disease. Additionally, bone scans help survey the different sites of involvement with polyostotic disease (see Image 18). Characteristically, a marked uptake of radiopharmaceutical in the involved bones is observed (see Image 19). However, late-stage involvement may not reveal intense radiopharmaceutical uptake, and osteoporosis circumscripta may demonstrate only a peripheral rim of increased uptake. Scintigraphy tends to follow the physiologic activity of disease and may monitor treatment. Polyostotic Paget disease often can be distinguished from multiple metastatic lesions, although occasional difficulties occur. Perform radiographic correlation when this situation arises. Furthermore, the diagnosis of fracture or sarcoma may be challenging, often requiring multimodality correlation.

INTERVENTION

Section 8 of 10  

• Authors and Editors
• Introduction
• Differentials
• Radiograph
• CT SCAN
• MRI
• Nuclear Medicine
• Intervention
• Multimedia
• References

Biopsy often is needed to diagnose Paget sarcoma. In such cases, CT typically is the modality of choice for guidance.

Medical/Legal Pitfalls

• Secondary sarcomas may occur in approximately 1% of patients with Paget disease. Some argue that early diagnosis of these lesions may not confer significant benefit to patients because of the poor prognosis associated with the lesions. However, lesions discovered in the extremities may be resected with positive results, and delayed diagnosis may affect the prognosis for cure or prolonged survival. Short-term interval follow-up and/or cross-sectional imaging may prevent diagnostic errors and initiate prompt attention to a newly developing lesion.

MULTIMEDIA

Section 9 of 10  

• Authors and Editors
• Introduction
• Differentials
• Radiograph
• CT SCAN
• MRI
• Nuclear Medicine
• Intervention
• Multimedia
• References

Media file 1:  Photomicrograph of bone involved with late-stage Paget disease demonstrates intersecting remodeling lines forming a mosaic pattern.
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Media file 2:  Lateral radiograph of the tibia in a patient with Paget sarcoma reveals a destructive bone-forming mass in the proximal tibia (osteosarcoma).
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Media file 3:  Anteroposterior radiograph of the hip in a patient with Paget disease demonstrates dense sclerosis involving the femoral head and neck (arrows). This is a high-risk area for insufficiency fracture.
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Media type:  X-RAY

Media file 4:  Anteroposterior radiograph of the femur in a patient with late-stage Paget disease reveals a transverse insufficiency fracture through the proximal femoral shaft (banana fracture).
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Media file 5:  Lateral skull radiograph in a patient with Paget disease demonstrates a large, well-circumscribed lytic lesion (arrows) in the frontal and parietal bones (osteoporosis circumscripta).
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Media type:  X-RAY

Media file 6:  Lateral radiograph of the calvarium in a patient with Paget disease reveals multiple patches of sclerotic bone in the calvarium (cotton wool appearance).
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Media file 7:  Lateral radiograph of the lumbar spine in a patient with Paget disease demonstrates enlargement of an involved vertebral body (arrow), with sclerosis more prominent at the vertebral endplates (picture frame vertebra).
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Media type:  X-RAY

Media file 8:  Lateral radiograph of the upper thoracic spine reveals a densely sclerotic vertebral body (ivory vertebra) caused by Paget disease (arrow). The appearance mimics findings that can be observed with malignant neoplasm such as lymphoma or metastatic disease.
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Media file 9:  Anteroposterior radiograph of the pelvis demonstrates thickening of the right iliopectineal line (small arrows), as well as later-stage involvement with Paget disease, including trabecular coarsening and patchy sclerosis (large arrow).
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Media file 10:  Anteroposterior radiograph of the right hip, coned down on the obturator ring, reveals patchy sclerosis and disorganized coarsened trabecula characteristic of late-stage Paget disease. An insufficiency fracture of the ischium inferior to the acetabulum (arrows) is present.
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Media file 11:  Coned down anteroposterior radiograph of the knee demonstrates an abnormal lucency in the distal femur with a flame-shaped or "blade of grass"-shaped proximal margin caused by the advancing lytic phase of Paget disease (black arrows). Courtesy of Lee F. Rogers.
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Media file 12:  Lateral coned down radiograph of the tibia reveals replacement of the tibial tubercle with pagetic bone that has mixed osteolysis and sclerosis (arrows).
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Media file 13:  Anteroposterior radiograph of the distal forearm demonstrates mixed-phase Paget disease in the distal radius with lytic disease proximally (white arrows) and coarsened trabeculae more distally (black arrow).
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Media file 14:  Anteroposterior radiograph of the proximal femur involved with intermediate (mixed phase) Paget disease reveals characteristic insufficiency fractures on the convex surface of the bone (arrow).
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Media file 15:  CT image of the first sacral vertebra demonstrates marked cortical thickening (arrows) and trabecular coarsening. Courtesy of Lee F. Rogers.
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Media file 16:  Axial T1-weighted MRI of the knee in a patient with Paget disease reveals prominent dark lines in the medullary bone, indicating trabecular coarsening (arrows). Courtesy of Lee F. Rogers.
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Media file 17:  Sagittal T1-weighted MRI of the lumbar spine demonstrates enlargement of the fourth lumbar vertebral body with no central canal encroachment (arrows). Courtesy of Lee F. Rogers.
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Media type:  MRI

Media file 18:  Whole-body bone scan in a patient with polyostotic Paget disease reveals intense uptake of radiopharmaceutical in the femur, pelvis, spine, and proximal right humerus. The cortical discontinuity of the proximal right humerus represents an insufficiency fracture (arrow). Courtesy of Lee F. Rogers.
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Media file 19:  Anterior image of the thoracic and lumbar spine in a 75-year-old man demonstrates intense radiopharmaceutical uptake in the third lumbar vertebra, which is involved with Paget disease (arrows). Courtesy of Lee F. Rogers.
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REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Differentials
• Radiograph
• CT SCAN
• MRI
• Nuclear Medicine
• Intervention
• Multimedia
• References

1. Paget J. On a form of chronic inflammation of bones (osteitis deformans). Med Chir Tr. 1877;60:37.
2. Singer FR. Update on the viral etiology of Paget''s disease of bone. J Bone Miner Res. Oct 1999;14 Suppl 2:29-33. [Medline].
3. Barker DJ. The epidemiology of Paget''s disease of bone. Br Med Bull. Oct 1984;40(4):396-400. [Medline].
4. Siris ES, Ottman R, Flaster E. Familial aggregation of Paget''s disease of bone. J Bone Miner Res. May 1991;6(5):495-500. [Medline].
5. Layfield R. The molecular pathogenesis of Paget disease of bone. Expert Rev Mol Med. 2007;9(27):1-13. [Medline].
6. Guyer PB, Chamberlain AT. Paget''s disease of bone in two American cities. Br Med J. Apr 5 1980;280(6219):985. [Medline].
7. Barker DJ, Clough PW, Guyer PB. Paget''s disease of bone in 14 British towns. Br Med J. May 7 1977;1(6070):1181-3. [Medline].
8. Schmorl G. Ueber Ostitis deformans Paget. Virchows Arch. 1932;283:694-751.
9. Rojas-Villarraga A, Patarroyo PA, Contreras AS, Restrepo JF, Iglesias-Gamarra A. Paget disease of bone in Colombia and Latin America. J Clin Rheumatol. Apr 2006;12(2):57-60. [Medline].
10. Harrington KD. Surgical management of neoplastic complications of Paget''s disease. J Bone Miner Res. Oct 1999;14 Suppl 2:45-8. [Medline].
11. Smith J, Botet JF, Yeh SD. Bone sarcomas in Paget disease: a study of 85 patients. Radiology. Sep 1984;152(3):583-90. [Medline].
12. Deyrup AT, Montag AG, Inwards CY, Xu Z, Swee RG, Krishnan Unni K. Sarcomas arising in Paget disease of bone: a clinicopathologic analysis of 70 cases. Arch Pathol Lab Med. Jun 2007;131(6):942-6. [Medline].
13. , Sharma H, Mehdi SA, MacDuff E, Reece AT, Jane MJ. Paget sarcoma of the spine: Scottish Bone Tumor Registry experience. Spine. May 20 2006;31(12):1344-50. [Medline].
14. Hamdy RC. Paget's Disease of the Bone: Assessment and Management. Westport, CT:. Greenwood Publishing Group;1981.
15. Gebhart M, Vandeweyer E, Nemec E. Paget''s disease of bone complicated by giant cell tumor. Clin Orthop. Jul 1998;(352):187-93. [Medline].
16. Altman RD, Collins B. Musculoskeletal manifestations of Paget''s disease of bone. Arthritis Rheum. Oct 1980;23(10):1121-7. [Medline].
17. Tiegs RD. Paget''s disease of bone: indications for treatment and goals of therapy. Clin Ther. Nov-Dec 1997;19(6):1309-29; discussion 1523-4. [Medline].

Article Last Updated: Dec 12, 2007