Introduction
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.
Presentation
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.
Differential Diagnoses
Bone Metastases
Fibrous Dysplasia
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
More on Paget Disease |
 Overview: Paget Disease |
| Imaging: Paget Disease |
| Follow-up: Paget Disease |
| Multimedia: Paget Disease |
| References |
| Next Page » |
References
Paget J. On a form of chronic inflammation of bones (osteitis deformans). Med Chir Tr. 1877;60:37.
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].
Barker DJ. The epidemiology of Paget''s disease of bone. Br Med Bull. Oct 1984;40(4):396-400. [Medline].
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].
Layfield R. The molecular pathogenesis of Paget disease of bone. Expert Rev Mol Med. 2007;9(27):1-13. [Medline].
Guyer PB, Chamberlain AT. Paget''s disease of bone in two American cities. Br Med J. Apr 5 1980;280(6219):985. [Medline].
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].
Schmorl G. Ueber Ostitis deformans Paget. Virchows Arch. 1932;283:694-751.
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].
Harrington KD. Surgical management of neoplastic complications of Paget''s disease. J Bone Miner Res. Oct 1999;14 Suppl 2:45-8. [Medline].
Smith J, Botet JF, Yeh SD. Bone sarcomas in Paget disease: a study of 85 patients. Radiology. Sep 1984;152(3):583-90. [Medline].
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].
, 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].
Hamdy RC. Paget's Disease of the Bone: Assessment and Management. Westport, CT:. Greenwood Publishing Group;1981.
Gebhart M, Vandeweyer E, Nemec E. Paget''s disease of bone complicated by giant cell tumor. Clin Orthop. Jul 1998;(352):187-93. [Medline].
Altman RD, Collins B. Musculoskeletal manifestations of Paget''s disease of bone. Arthritis Rheum. Oct 1980;23(10):1121-7. [Medline].
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].
Further Reading
Keywords
osteitis deformans, Paget's disease
