Pharmacologic management of Paget's disease

The pathogenesis, clinical features, indications for therapy, and current pharamacologic management of Paget's disease are reviewed. Paget's disease is a bone disorder of unknown etiology primarily affecting the elderly. Overactive bone resorption leads to the accelerated formation of disorganized, weak bone. Pain and fractures are common clinical features. Neurologic, cardiovascular, metabolic, and neoplastic complications are also reported. Because most patients are asymptomatic, the disease is often detected during routine roentgenography or laboratory tests. Primary indications for pharmacologic intervention include bone pain, neural compression, immobilization hypercalcemia or hypercalciuria, cardiac failure, and orthopedic surgery. Recurrent or non-healing fractures and rapidly progressing complications are additional indications. Drugs used in the management of Paget's disease include calcitonin, etidronate disodium, and plicamycin. Although these agents are efficacious, each has disadvantages. Clinical resistance to animal calcitonins may develop, and the cost of therapy may be prohibitive. Etidronate may induce ostemalacia. The use of plicamycin is limited by potentially severe toxicities. Dichloromethylene and aminohydroxypropylidene are promising diphosphonate compounds but are still investigational In those patients who are unresponsive to single-agent regimens, combination therapy may prove effective. Although many patients with Paget's disease do not require pharmacologic therapy, calcitonin and etidronate are the agents of choice when it is indicated.