Paget's disease of bone is a condition of disorganized growth of bone which may occur in one or many bones throughout the body. Complications of this disease may include bone deformity, pain, fractures of bone, neoplastic degeneration, osteoarthritis, deafness and central nervous system problems. Many patients with Paget's disease have no symptoms, however.

Paget's disease affects up to 3% of people over age 55 in Europe and North America, but is rare in Asia. It is thought to result from a late complication of viral infection.

Paget's disease is frequently diagnosed with the finding of a high alkaline phosphatase in a biochemical profile. It is easily diagnosed on x-ray and bone scan by its characteristic appearance. Markers for the presence and activity of Paget's disease include serum alkaline phosphatase concentration in urine hydroxyproline excretion; however, these values may occasionally be normal in patients with single bone disease (15% incidence). The rate of bone resorption can also be quantified by the determination of urinary excretion of pyridinoline.

Drug therapy for Paget's disease has been recently revolutionized. Salmon calcitonin may be given by injection or now by nasal spray. However, resistance to calcitonin treatment does develop in many patients. A class of agents known as bisphosphonates has been developed and new drugs are under study. Itidronate (Didronel) has been effective for Paget's disease, but occasionally causes bone pain in patients with some aggressive forms of Paget's disease. Pamidronate (Aredia) has been developed for intravenous use. Alendronate (Fosamax) in doses up to 40 mg daily orally has been extremely effective, but esophageal and gastrointestinal side effects relatively common and the medication must be taken at least one-half hour before breakfast with only water; patients must be in the upright position and not go back to bed after taking this medication. Other drugs that are available in some countries include clodronate which has both oral and intravenous preparations; tiludronate (Skelid) is another oral preparation that is available in some countries.

Now undergoing development in clinical trials include a number of new medications which promise to have increased effectiveness and decreased side effects. These medications include neridronate, olpadronate, risedronate, ibandronate, and zoledronate (intravenous).

Indications for drug therapy for patients with Paget's disease include bone or joint pain, bone deformity, joint or neurologic complications, and patients with asymptomatic disease, but who are at risk for complications due to the site of the disease. Such sites include the base of the skull which may cause risk of hearing loss or other neurologic complications, the spine due to risk of neurologic complications and long bones in lower limbs due to the risk of fracture and osteoarthritis. It is also recommended that patients be prepared with drug therapy prior to undergoing orthopedic surgery in order to reduce bleeding complications.

Selection of therapy includes a bisphosphonate as the first line treatment. Calcitonin is also used. Patients receiving treatment with bisphosphonates, whether oral or intravenous, require daily supplementation with calcium and vitamin D in order to prevent osteomalacia and secondary hyperparathyroidism.

Beethoven was considered to have had Paget's disease. It ironically caused deafness during the latter part of his composing life. Paget's disease has had serious morbidity and has been under-recognized as an important disorder that needs proper diagnosis and treatment. The current and coming treatments noted above provide great hope for people suffering from Paget's disease. An excellent review article on Paget's disease was authored by Drs. Pierre Dalmas and Pierre Meunier of Lyon, France in the New England Journal of Medicine 1997 336:558-566.