When patients with Paget disease are immobilized, such as for surgery, hypercalcemia may result. Other conditions that have been associated with hypercalcemia in patients with Paget disease include fractures, hyperparathyroidism, hyperthyroidism, or unrelated carcinoma with skeletal metastases. Paget sarcoma is a rare complication occurring in fewer than 1% of cases and rarely before 70 years of age. Severe night pain in the area of previous pagetic involvement in an elderly patient as well as radiographic evidence of bone destruction should merit further evaluation for sarcoma.

DIAGNOSIS

Paget disease is diagnosed based on radiographic and biochemical findings. If radiographic findings are not diagnostic, further evaluation with computed tomography or MRI may be employed, but bone biopsy is rarely necessary for the diagnoses.

Radiologic appearance of Paget disease is characteristic and frequently diagnostic. In the early stages the disease is characterized by osteolytic lesions that appear as areas of bone loss in the skull or long bones. When the disease is left untreated, progression from the osteolytic phase to the combined lytic/sclerotic phase is demonstrated by cortical thickening, accentuated trabecular markings, and loss of corticomedullary distinction. The bone may appear abnormal in structure and is sometimes described as having a “cotton wool” appearance.

The key to the diagnosis of Paget disease is any elevated biochemical markers of bone turnover. These markers are helpful both in monitoring the disease progression as well as assessing response to therapy. The total serum alkaline phosphatase level is elevated in Paget disease, and other causes of elevated alkaline phosphatase including liver disease should be ruled out. The bone-specific alkaline phosphatase is elevated in up to 85% of patients with untreated Paget disease, and the levels may be related to the extensive skeletal involvement. Some patients with monostotic disease may exhibit normal serum alkaline phosphatase levels.

TREATMENT

The therapeutic goal in patients with Paget disease is to relieve symptoms such as bone pain and to prevent neurologic complications. In addition, medical treatment may be indicated for patients in whom surgery is planned in a region of pagetic bone in order to reduce blood flow to the area. Treatment with antiresorptive agents can be considered for asymptomatic patients to reduce the likelihood of disease progression in the future risk of skeletal deformity, neurologic complications, hearing loss, or secondary osteoarthritis.

Nonsteroidal anti-inflammatory medications may be used to manage the pain associated with Paget disease. Because antiresorptive therapy is efficacious, surgical treatment should be limited to the management of fractures, deformity, and secondary osteoarthritis.

Antiresorptive Therapy

The goal of Paget disease therapy with antiresorptive treatment is to decrease the rate of bone turnover at the pagetic site. Therapeutic efficacy can be assessed by following the biochemical markers of bone resorption in formation.

Bisphosphonates remain the cornerstone for the treatment of Paget disease and have been demonstrated to be both efficacious and to have, in general, an acceptable safety profile.