4.5 Additional Reading:Paget’s Disease
Definition
Paget’s disease（osteitis deformans）is a disorder of aging in which bones become overgrown and thicker，and deformed.The disease results in bowing of the long bones and distortion of the flat bones，such as those of the skull.The initial phase is characterized by markedly increased bone resorption，followed by exuberant new bone formation.This increased bone formation results in bone enlargement and deformity because of the poor quality of the bone.
Epidemiology and etiology
The cause of Paget’s disease is unknown.However，a genetic predisposition has been clearly established.Approximately 40%of patients with Paget’s disease have an affected first-degree relative，and many families with vertical transmission of Paget’s disease and an autosomal dominant pattern of inheritance have been described.
Although Paget’s disease is the second most common bone disease，its prevalence varies among different populations.In the United Kingdom，for instance，Paget’s disease affects up to 6%of the population older than 55 years.Further，the frequency of symptomatic Paget’s disease increases with age.Paget’s disease occurs with similar prevalence in Western Europe and in the white populations of New Zealand and Australia.However，Paget’s disease is extremely rare in Scandinavia and the Far East，and it does not affect indigenous populations in either Australia or New Zealand.
Clinical manifestations
Most patients with Paget’s disease are elderly，and the age at diagnosis is usually older than 50 years.Paget’s disease affects both men and women，with a slight male predominance.Although Paget’s disease is often asymptomatic，10%to 30%of patients experience pain，skeletal deformity，neurologic symptoms，pathologic fractures，or deafness.Patients may have only one affected bone or pagetic lesions in multiple bones.Patients with familial Paget’s disease tend to have more bones affected and more deformity than those with sporadic Paget’s disease.Paget’s disease remains highly localized，and patients rarely develop new lesions in previously unaffected bones after diagnosis.
Diagnosis
The biochemical findings in Paget’s disease reflect the cellular events occurring throughout the skeleton of the affected patients.Measurement of collagen cross-link degradation products in urine provides a specific measure of skeletal matrix degradation.Urinary N-telopeptide，pyridinoline，and deoxypyridinoline have all been used as measures of skeletal matrix resorption.Serum tartrate-sensitive acid phosphatase，released by osteoclasts，is another index of bone resorption in Paget’s disease.Osteoblast activity can be assessed by measuring total serum alkaline phosphatase activity，serum bone-specific alkaline phosphatase concentration，serum osteocalcin concentration，and serum type 1 carboxy-terminal procollagen peptide concentration.
Treatment(https://www.daowen.com)
Symptomatic patients with Paget’s disease require treatment.No data support the treatment of asymptomatic patients，except in the presence of rapidly advancing osteolytic lesions in weight-bearing long bones，in which case the risk of pathologic fractures is increased.Because the osteoclast is the primary cell involved in Paget’s disease，medical treatment that inhibits osteoclast activity—in particular，the use of bisphosphonates，calcitonin，and mitomycin—has been successful.Salmon calcitonin by injection，which has been used since the early 1980s，is an effective treatment for Paget’s disease，suppressing the biochemical parameters of the disease by 50%.Bisphosphonates can inhibit osteoclast formation，but they predominantly induce osteoclast apoptosis；they are the most frequently used treatment for Paget’s disease.Bisphosphonates，which contain nitrogen，are pyrophosphate derivatives with a high affinity for bone.They are incorporated into sites of bone resorption，released during the resorption process，and taken up by osteoclasts.This process results in the death of osteoclasts.Osteoclasts were recently reported to be angiogenic，and bisphosphonates affect angiogenesis as well as cytokine production by osteoclasts.Some treatments may result in a high degree of normalization of both skeletal abnormalities and bone scan findings in these patients.With the availability of more potent bisphosphonates，the prognosis has greatly improved.A single intravenous dose of 5 mg of zoledronic acid can provide a 96%response rate for the next 6 months and is more effective than 2 months of oral risedronate.
Patients treated with bisphosphonates can usually attain remission.Symptomatic bisphosphonate treatment for pagetic bone pain unresponsive to analgesics or antiinflammatory drugs is as good as repeat courses of bisphosphonates，irrespective of symptoms，in reducing and maintaining normal alkaline.However，after variable periods of time，patients suffer relapse and require further treatment.Bisphosphonates by themselves have not been shown to“cure”Paget’s disease.However，treatment with zoledronate can result in very long remissions.
Surgery is used to treat fractures，correct the deformity of bowed bones，and treat bone disease in the hip.In addition，surgical treatment may relieve the neurologic complications of the overgrowth of pagetic bone，with resultant nerve root compression.Before elective surgery，patients with Paget’s disease are usually treated with bisphosphonates to decrease the vascularity and activity of the bone and to prevent increased bleeding.
Prognosis
Pagetic bone pain responds to medical treatment.Much of the bone pain associated with the disease results from arthritis or joint pain arising from the bone deformity，rather than pain from the pagetic bone per se.Unless treated，pagetic lesions continue to increase in size，but patients rarely if ever develop new lesions in previously unaffected bones.In patients for whom analgesic or other specific treatments are unsuccessful，joint replacement can be performed.The most dreaded complication of Paget’s disease is the development of osteosarcoma in the pagetic lesion.Although it is an extremely rare complication，affecting less than 1%of patients，Paget’s disease is the most common cause of osteosarcoma in adults.Once patients develop osteosarcoma，their prognosis is extremely poor，and the outcome is usually fatal.Active treatment of Paget’s disease decreases the biochemical abnormalities and improves the neurologic syndromes associated with this disease.
（969 words）
Task 9 Identify the word elements and define the meaning of each medical term.
Continued
