ESSENTIALS OF DIAGNOSIS
Bone pain may be the first symptom.
Kyphosis, bowed tibias, large head, deafness, and frequent fractures.
Serum calcium and phosphate normal; elevated alkaline phosphatase and urinary hydroxyproline.
Dense, expanded bones on radiographs.
Paget disease of bone is manifested by one or more bony lesions having high bone turnover and disorganized osteoid formation. The involved bone first has increased osteoclast activity, causing lytic lesions in bone that may progress at about 1 cm/year. Increased osteoblastic activity follows, producing a high rate of disorganized bone formation. Involved bones become vascular, weak, and deformed. Eventually, there appears to be a final burned-out phase with markedly reduced bone cell activity and abnormal bones that may be enlarged with skeletal deformity.
The prevalence of Paget disease has declined by about 36% over the past 20 years, yet it is the second most common bone disease after osteoporosis. Paget disease has a striking geographic variation in prevalence. It is most common in the United Kingdom and in areas of European migration, particularly New Zealand, Australia, the United States, South Africa, Quebec, and Brazil. Interestingly, the disease appears equally common among different races in these countries. In the United States, Paget disease affects 3% of whites over age 55 years, with its prevalence increasing with age. It is uncommon in Africa, Asia, and Scandinavia. Usually diagnosed in patients over age 40 years, its prevalence doubles with each decade thereafter, reaching an incidence of about 10% after age 80. About 20% of cases are symptomatic, but most cases are discovered incidentally during radiology imaging or because of incidentally discovered elevations in serum alkaline phosphatase.
The cause of Paget disease is unknown. About 20% of cases are familial and transmitted as an autosomal dominant trait with incomplete penetrance. Mutations in the SQSTM1 gene have been discovered in about 35% of patients with familial Paget disease and in 7% of patients with apparently sporadic Paget disease.
Paget disease is often mild and asymptomatic. Only 27% of affected individuals are symptomatic at the time of diagnosis. Paget disease involves multiple bones (polyostotic) in 72% and only a single bone (monostotic) in 28%. It occurs most commonly in the pelvis, vertebrae, femur, humerus, and skull. The affected bones are typically involved simultaneously, and the disease tends not to involve additional bones during its course. Pain, often described as aching and deep and often worse at night, is the usual first symptom. It may occur in the involved bone or in an adjacent joint, which can be involved with degenerative arthritis. Paget disease typically first affects long bones proximally and then advances distally, with bone pain at the osteolytic front being aggravated by weight bearing. Joint surfaces (such as the knee) can be involved and cause arthritic pain. The bones can become soft, ...