Paget Disease Clinical Presentation

Paget disease is a localized disorder that may be monostotic (affecting only one bone) or polyostotic (affecting 2 or more bones). Monostotic disease accounts for 10-35% of cases.

Paget disease has a predilection for the axial skeleton. The condition commonly affects the pelvis and spine, particularly the lumbar spine, with a frequency of 30-75%. The sacrum is involved in 30-60% of cases and the skull in 25-65% of cases. The proximal long bones, especially the femur, also are frequently affected (25-35% of cases). Involvement of the shoulder girdle and proximal humerus is not uncommon. Though any bone may be affected, the fibula, ribs, and bones in the hands and feet are involved infrequently.

Paget disease does not spread from one bone to another, and new sites of involvement are rare after the initial diagnosis. Instead, lesions may continue to progress if left untreated.

Most persons with Paget disease are asymptomatic. ^[23] In these patients, the incidental finding of an elevated serum alkaline phosphatase level or characteristic radiographic abnormality may lead to detection of the disease. However, when symptoms do occur, bone pain is the most common complaint. The bone pain is dull, constant, boring, and deep below the soft tissues. It may persist or exacerbate during the night.

Hip pain is most common when the acetabulum and proximal femur are involved, especially in the sclerotic stage. Bowing of the femur and long bones or protrusion of the acetabulum causes pain that becomes worse with weightbearing and is relieved with rest. Knee and shoulder pain may occur because of altered mechanical forces across the articular joints from deformed bones.

Other patients with Paget disease present with a range of manifestations related to complications. These include musculoskeletal, neurologic, and cardiovascular problems.

Pathologic fractures commonly result from weakened pagetic bone. Subtrochanteric femur fractures are the most common fractures affecting the lower limbs.

Nonspecific headaches, impaired hearing, and tinnitus commonly result from skull involvement. The patient's hat size may increase (or, less commonly, decrease) as a result of skull enlargement or deformity.

The most common cranial symptom is hearing loss, occurring in 30-50% of patients with skull involvement. The most common neurologic complication is deafness as a result of involvement of the petrous temporal bone. The hearing loss or deafness may be conductive (due to involvement of the middle-ear ossicles), sensorineural (due to auditory nerve compression/cochlear involvement), or mixed. Vertigo or tinnitus may occur with a frequency of 25% in patients who have Paget disease with cranial involvement.

Cranial nerve palsies can affect nerves other than the auditory nerve; however, this development is uncommon. Changes in vision may occur secondary to optic nerve involvement.

Back and neck pain are common complaints, as Paget disease frequently affects the spine, especially the lumbar and sacral regions. Softened bone at the base of the skull may lead to platybasia, the descent of the cranium onto the cervical spine. Progressive pain, paresthesias, limb paresis, gait difficulties, or bowel and bladder incontinence may be caused by compression of the spinal cord or spinal nerve secondary to platybasia or vertebral fractures.

Skull deformities may lead to hydrocephalus, basilar invagination, and cerebellar or brainstem compressive syndromes. These may manifest as nausea, dizziness, syncope, ataxia, incontinence, gait disturbances, or dementia.

Involvement of the jaw and facial bone is uncommon in Paget disease, but it does occur. Facial disfigurement and malocclusion may be observed following enlargement of the maxilla or mandible. Tooth loss may occur with progressive root resorption. Absent periodontal membranes and lamina dura are associated with excessive cementum formation.

Increased bone pain with an enlarging soft tissue mass and a lytic lesion is suggestive of a neoplasm (osteosarcoma), especially if a pathogenic fracture is present. This is an uncommon but potentially deadly complication.

The physical examination findings may be normal in patients with Paget disease. In symptomatic cases, visual inspection may reveal bony deformities, such as an enlarged skull, spinal kyphosis, and bowing of the long bones of the extremities. Bone angulation and deformity may affect joints, with resulting pain and decreased range of motion. Because patients with Paget disease may also have gouty arthritis, they also should be evaluated for the presence of tophi.

Localized pain and tenderness may be elicited with manual palpation. Superficial pressure reveals increased warmth of the skin at the affected site. Skin temperature may be correlated with metabolic activity of underlying bone and bone pain. Auscultation may reveal bruits of the tibia or skull. A soft tissue mass with increased pain may be caused by neoplasms, such as osteosarcoma.

Paget disease of the skull may be asymptomatic; however, approximately one third of patients experience an increase in head size with or without deformity (frontal bossing, enlarged maxilla). The most common neurologic problem is hearing loss from compression of cranial nerve VIII and cochlear dysfunction. If the facial bones are affected, a patient may have facial deformity problems and, rarely, narrowing of the airway. Ataxia, gait disturbances, dementia, and neurologic compromise may result from hydrocephalus and cerebellar compression.

With involvement of the lumbar spine, spinal stenosis or kyphosis may develop. If Paget disease affects the thoracic spine, the patient may have spinal cord compression, which can lead to neural function loss. Muscle weakness, paraparesis, and sensory loss compatible with spinal cord injury (SCI) may be present.

Fracture of a pagetic bone is an occasional and serious complication and may be either traumatic or spontaneous. The femur is the most common site of pagetic fracture. Most pagetic bone fractures heal normally.

Complications of Paget disease include the following:

• Fractures
• Neoplasms
• Neuromuscular syndromes
• Joint disease
• Cardiovascular abnormalities

Angioid streaks of the retina have been found more commonly in patients with Paget disease and are quite frequent in pseudoxanthoma elasticum. Angioid streaks are linear disruptions of the Bruch membrane, with proliferative connective tissue emerging through the defects.

Other complications of Paget disease include the following:

• Hashimoto thyroiditis
• Dupuytren contracture
• Chondrocalcinosis
• Osteogenesis imperfecta
• Osteopetrosis

Fractures

Incomplete stress fractures frequently occur in Paget disease. Cortical stress fractures are common in the femur and tibia, with distinctive horizontal radiolucencies affecting the convex surface of the bone, whereas in osteomalacia, similar findings are seen on the concave aspects of the bone. Cartilaginous calluses, which do not mineralize fully in the fracture clefts, account for the relative radiolucency. Incomplete fissure fractures can extend into complete fractures.

Mild injuries may cause acute true pathologic fractures in weakened pagetic bone. Pathologic fractures are more common in women than in men. The most frequent site of these fractures is the femur, but fractures commonly occur in the tibia, humerus, spine, and pelvis. Femur fractures are most common in the subtrochanteric region, followed by the upper third of the femoral shaft and then the neck.

Nonunion and refracture at the same sites are much more common, as developing calluses may be affected by Paget disease. The rate of nonunion has been reported to be 40%. ^[25] Biopsies of pathologic fractures may be recommended to rule out sarcoma.

Neoplasm

Sarcomatous degeneration of pagetic bone is a deadly complication. Osteosarcoma is a rare complication, but it should be suspected in patients who have a sudden increase in bone pain or swelling. ^[26] Pagetic sarcoma is malignant, and the course usually is rapid and fatal. Sarcomatous degeneration may occur in 5-10% of patients with extensive pagetic skeletal involvement, but it may occur in less than 1% of patients with less widespread involvement.

Men are affected with sarcomatous degeneration slightly more frequently than are women. Peak incidence is in the seventh and eighth decades of life. The femur is the most commonly affected site, followed by the proximal humerus; however, no bone is exempt, including sites of previously healed fractures.

Sarcomas appear to originate from the fibrotic substrate of pagetic bone, and the predominance of certain cells determines the diagnosis. Osteosarcoma is the most common type of pagetic sarcoma (50-60%), followed by fibrosarcoma (20-25%), chondrosarcoma (10%), and sarcoma of myeloid and mesenchymal elements. Sarcomatous bone destruction or osteolysis is more characteristic of pagetic sarcoma than osteosclerosis. Overall, the proportion of Paget disease patients with sarcoma has fallen steadily since Paget's original report and is now about 0.3%, ^[26] likely related to availability of effective therapies.

Other clinical and radiographic findings include the following:

• Increased pain with a progressive lytic lesion
• An enlarging soft tissue mass
• Bony speculation
• Persistent fracture without healing
• Cortical destruction

In 33% of cases, the presentation involves a pathologic fracture of an affected long bone.

Giant cell tumors are benign and may arise from pagetic bone. They usually involve the facial bones and mandible, although other sites, such as the pelvis, may be affected in rare cases. Giant cell tumors commonly affect elderly patients. They share some characteristics of sarcomas, as they typically affect patients with widespread polyostotic Paget disease and present as a soft tissue mass with a lytic lesion.

The prognosis for patients with Paget disease who have giant cell tumors usually is good. High doses of steroids have been shown to reduce tumor mass. Radiation and surgery also have been used to treat symptomatic giant cell tumors.

Lymphomas, multiple myelomas, Hodgkin lymphoma, leukemias, and metastatic disease all have been found in association with Paget disease. However, these neoplasms probably represent chance occurrences rather than true complications.

Neuromuscular syndromes

Acute spinal cord compression may occur from pathologic fractures, such as vertebral body compression fractures. Enlargement of the pedicle, lamina, or vertebral body from the pagetic process also may cause spinal cord injury. Likewise, nerve root or spinal nerve compromise may occur. Spinal cord compression is most frequent in the upper thoracic spine because of the small vertebral canal.

Spastic quadriplegia can result from platybasia. Basilar invagination or compression of posterior fossa structures may lead to cerebellar or brainstem compressive syndromes. The vertebrobasilar blood supply also may be compromised by kinking of the blood vessels. Extradural fat ossification has been observed to be a cause of cauda equina syndrome. Hydrocephalus can be a complication, albeit a rare one.

Entrapment of cranial nerves by pagetic bone may result in the expected cranial nerve palsies. The most common of these is injury to the eighth cranial nerve (the vestibulocochlear nerve), with resultant impaired hearing and deafness. The hearing loss may be sensorineural, conductive, or mixed and may be caused by compression from pagetic bone involvement of the temporal bone and labyrinth. Structural abnormalities of the ossicles of the middle ear and toxic effects to the inner ear have been observed.

The optic nerve may be the second most commonly affected cranial nerve. Sciatic nerve compression between an enlarged ischium and lesser trochanter of the femur in external rotation or between the ilium and the piriformis muscle in internal rotation also has been described.

Joint disease

Degenerative joint disease is associated with Paget disease. The most commonly reported site of articular abnormality is the hip. The knee also is commonly affected. The glenohumeral joint also may be affected, impairing rotator cuff function.

Degenerative joint disease of the hip associated with Paget disease differs in appearance from primary degenerative joint disease. Osteophyte formation is not prominent.

The frequency of joint-space narrowing of the hip in patients with Paget disease varies in several studies from 50-96%. ^[27] Joint space loss at the superior aspect of the hip articulation is the most common pattern, with a frequency of 80-85%. Acetabular involvement may cause either medial or axial joint space narrowing, especially if the femoral head also is affected. Acetabular protrusion may occur, causing hip pain that is aggravated by ambulation.

The pathophysiology of arthritic changes associated with Paget disease is unknown. Enlargement of joints and altered biomechanics may cause abnormal stress across joints, giving rise to degenerative changes. Abnormal endochondral ossification that may compromise articular cartilage has been reported. For cases that require surgery, successful outcomes of total hip and knee arthroplasties have been reported.

Conditions that have been found to coexist with Paget disease, but that have no proven relationship with Paget disease, include the following:

• Rheumatoid arthritis
• Psoriatic arthritis
• Ankylosing spondylitis
• Diffuse idiopathic skeletal hyperostosis
• Pseudogout
• Peyronie disease
• Pigmented villonodular synovitis

Hyperuricemia may cause clinical gout in some patients.

Cardiovascular abnormalities

Increased cardiac output has been observed in patients with Paget disease involving at least 15% of the skeleton. Left ventricular hypertrophy is an associated finding. Increased soft tissue and pagetic bone vascularity has been implicated as a contributing factor. High-output congestive heart failure may occur, but it is rare. The condition has been reported only in patients with severe, widespread Paget disease.

Calcific aortic stenosis is 4 times more common in patients with Paget disease, especially those with severe disease, than in individuals without Paget disease. Calcifications may be produced by the turbulent blood flow across cardiac valves caused by increased cardiac output. Calcifications have been found in the interventricular septum, which may cause heart block and conduction abnormalities.