Paget's disease of bone: indications for treatment and goals of therapy

Paget's disease of bone is a common disorder of unknown etiology characterized by increased bone remodeling and abnormal bone architecture. The pathologic process is initiated by an increase in osteoclast-mediated bone resorption, accompanied by a compensatory increase in bone formation. The increased bone remodeling results in a disorganized mosaic of woven and lamellar bone. This bone is highly vascular and gradually becomes enlarged and structurally weakened. Paget's disease is generally diagnosed in patients older than 40 years of age, usually as an incidental finding. The disease may be monostotic or polyostotic. The pelvis, femur, spine, tibia, skull, and humerus are most commonly involved. Most patients with Paget's disease are asymptomatic. Pain is the most common presenting symptom. Complications of the disease include bowing deformity of the long bones, fracture, and a variety of nerve compression syndromes. Malignant degeneration of Paget's disease is a rare complication. As safer, more effective therapies have become available, the indications for treatment and goals of therapy have changed. The difficult issue that clinicians are currently facing is whether to treat patients with asymptomatic disease. The progressive nature of the disease, the severity of its complications, its potential negative impact on quality of life, and the availability of therapy capable of controlling its activity have led many experts in the field to recommend treatment of asymptomatic patients who have active disease at sites where complications are likely to develop. There are, however, no data to prove that complications can be prevented by decreasing the rate of bone remodeling in Paget's disease, nor any data to define who is at risk for complications. Until more information is available, the management of patients with Paget's disease will continue to be based on clinical observation and theoretical considerations. This review examines the present understanding of Paget's disease, the rationale for the proposed indications for treatment and the goals of therapy.