Paget disease of bone is a localized skeletal disorder that is characterized by an increased number of osteoclasts that are large in size and contain multiple nuclei. These osteoclasts exhibit excessive activity and cause accelerated bone resorption that is tightly coupled to the recruitment of osteoblasts to the resorbed area. The result is excessive formation of disorganized osteoid tissue that is mechanically weaker, resulting in bone that is prone to deformity and fracture.

The clinical complications of the disease include bone pain, skeletal deformity, hearing loss, osteoarthritis, neurologic complications, and fractures. The skeletal sites most likely to be affected are the skull, spine, upper extremity, lower extremity, and pelvis.

Although oral bisphosphonates had been the most widely prescribed agents for the treatment of Paget disease, their use was limited by complicated dosing regimens and gastrointestinal complications. Fortunately, the advent of intravenous bisphosphonate therapy has revolutionized the treatment of this disease and has provided many patients with long-term remissions.

ETIOLOGY

The etiology of Paget disease remains unknown. Familial cases display an autosomal dominant pattern of inheritance with variable penetrance. Studies of familial patch disease have identified several susceptibility loci, including 2q36, 5q31, 5q35, 10p13, 18q21-22, and 18q23, whereas some recent investigations have focused on the sequestosome gene (SQSTSM1) on chromosome 5. However, nongenetic factors may also be involved. In 1974, some investigators demonstrated nuclear and cytoplasmic inclusion bodies in the osteoclasts of some patients with Paget disease that seemed to resemble viral particles. Electron microscopy confirmed the presence of pagetic osteoclasts with nuclear and cytoplasmic virus-like inclusion bodies resembling paramyxovirus nuclear capsids. However, this viral hypothesis remains controversial because multiple studies failed to demonstrate the presence of viruses in bone marrow cells or pagetic osteoclasts.

CLINICAL MANIFESTATIONS

Most patients with Paget disease do not initially present with clinical symptoms, and the diagnosis is frequently made as an incidental finding on radiographs or laboratory tests. Paget disease can affect one bone (monostotic) or multiple bones (polyostotic). The skeletal sites most commonly affected are the pelvis (70%), femur (55%), lumbar spine (55%), skull (42%), and tibia (32%).

The skeletal deformities that can result include bowing of the long bones, increased skull size, dilated skull veins, hearing loss, and increased skin temperature over the affected long bones. Osteoarthritis with resultant pain of the knee or hip that occurs adjacent to the pagetic bone is commonly reported by patients with Paget disease. The pain is frequently described as deep and aching and persists during the night, which may help differentiate it from other forms of osteoarthritis. Femur and tibia pain may be exacerbated by weightbearing activity.

Involvement of the skull may be associated with headaches, tinnitus, vertigo, and dilated scalp veins. When the jaw is involved with Paget disease, dental complications can include loosening of the teeth or swollen gums. Spinal involvement may result in vertebral enlargement or compression fractures as well as kyphosis. Because of the disorganized osteoid tissue in Paget disease, the bone is prone to fracture after only minimal trauma. Long bones may be associated with transverse rather thin spiral fractures.