Clinical Pearls: Paget's Disease

Paget’s disease of bone may present with bone pain but is often asymptomatic. Treatment (typically with bisphosphonates) is indicated in patients with pain that is localized to an affected site but not in asymptomatic patients.

Paget’s disease of bone is a common disorder characterized by focal areas of increased and disorganized bone remodeling affecting one or more bones throughout the skeleton.

Clinical Pearls

•  What is the epidemiology of Paget’s disease and what bones does it preferentially target?
Paget’s disease is rare before the age of 55 years, but increases in prevalence thereafter, in some countries affecting about 5% of women and 8% of men by the eighth decade of life. The disease predominantly affects people of European descent and is rare in Africans, people from the Indian subcontinent, and Asians. It preferentially targets the axial skeleton, most frequently affecting the pelvis (70% of cases), femur (55%), lumbar spine (53%), skull (42%), and tibia (32%).
•  What are the signs and symptoms of Paget’s disease?
The first indication of Paget’s disease of bone is typically an elevated serum alkaline phosphatase level or an abnormal radiograph in a patient whose health is being investigated for other reasons. Between 30 and 40% of patients have symptoms at the time of diagnosis, although the overall proportion of patients with symptoms is believed to be substantially lower (5 to 10%), since many cases never come to medical attention. The most common symptom is bone pain, which may be due to increased bone turnover or a complication such as osteoarthritis, spinal stenosis, or pseudofracture. Deafness may occur in patients with skull involvement. Osteosarcoma is a rare complication (present in less than 0.5% of cases) but should be suspected in patients who have a sudden increase in bone pain or swelling.

Morning Report Questions

Q: How is the diagnosis of Paget’s disease made?    
A: The diagnosis can usually be made on the basis of a radiograph showing the typical features of focal osteolysis with coarsening of the trabecular pattern, bone expansion, and cortical thickening. The extent of disease is best determined on radionuclide bone scans, which can be helpful in assessing symptoms that develop at sites distant from the site of pain at presentation. The use of magnetic resonance imaging or computed tomography is not routinely indicated, although it does have a role in selected patients in whom complications such as spinal stenosis or osteosarcoma are suspected. Typically, patients with Paget’s disease of bone present with an isolated elevation in the alkaline phosphatase level, with otherwise normal results of biochemical testing. However, normal levels of alkaline phosphatase do not rule out the diagnosis.

Q: How is Paget’s disease treated?
A: The drugs of first choice in the treatment of Paget’s disease of bone are nitrogen-containing bisphosphonates (aminobisphosphonates) such as alendronate, pamidronate, risedronate, and zoledronic acid, which preferentially target affected sites and are highly effective at suppressing the increased bone turnover that is characteristic of active Paget’s disease. Randomized trials have shown aminobisphosphonates to be superior to simple bisphosphonates such as etidronate and tiludronate in suppressing bone turnover in Paget’s disease, but not in improving symptoms. Levels of alkaline phosphatase start to fall within about 10 days after the commencement of bisphosphonate treatment and reach a nadir between 3 and 6 months. There is no evidence that asymptomatic patients benefit from antiresorptive therapy.