Paget’s disease of bone
1. What is Paget’s disease of bone?
Paget’s disease affects approximately 1.5 million people in the United States. It is characterized by abnormal bone architecture resulting from an imbalance between osteoblastic bone formation and osteoclastic bone resorption. Skeletal remains indicate that Paget’s disease first appeared in Western European populations during the Roman period. Sir James Paget first described this disease in 1876, and he called the condition osteitis deformans. We now know that Paget’s disease of bone is not an inflammation of bone (osteitis) and only rarely results in deformity.
2. Discuss how Paget’s disease is diagnosed.
The diagnosis of Paget’s disease is generally based on a combination of clinical manifestations, radiographic signs, and characteristic biochemical changes. Although histologic examination of pagetic bone is diagnostic, a bone biopsy is often unnecessary. Bone biopsy should be performed when the diagnosis of Paget’s disease is unclear or when osteogenic sarcoma or metastatic carcinoma must be excluded.
3. What are the clinical manifestations of Paget’s disease?
Most patients (70%-80%) with Paget’s disease are asymptomatic. This disorder is often suspected from radiographs performed for other reasons or from an unexpected elevation of the serum alkaline phosphatase concentration. The most common symptom of Paget’s disease is bone or joint pain. The pain is often described as dull and aching. Other manifestations of Paget’s disease, such as headache, bone deformity, skull enlargement, fracture, change in skin temperature over an involved bone, high-output congestive heart failure, and entrapment neuropathies that may cause hearing loss or other neurologic deficits, are much less common (Box 12-1). Neurologic deficits may arise from bony impingement on the brain or cranial nerves exiting from the skull, spinal nerve entrapment, or direct pressure of pagetic vertebrae on the spinal cord. Bone deformity is usually seen in patients with long-standing Paget’s disease. Most commonly, the skull, clavicles, and long bones are deformed and exhibit both an increase in size and an abnormal contour. There is speculation that Ludwig van Beethoven’s hearing loss, headaches, and progressive hyperostosis frontalis were the results of advanced Paget’s disease of bone.
4. What disorders are associated with Paget’s disease of bone?
Several disorders are more prevalent in patients with Paget’s disease than in unaffected individuals. They include arthritis, fractures, primary hyperparathyroidism, osteoporosis, thyroid disease, and kidney stones.
5. What are the three phases of Paget’s disease of bone?
Paget’s disease progresses through three distinct phases. The initial phase is an osteolytic phase characterized by predominantly osteoclastic bone resorption. Approximately 1% to 2% of patients exhibit this purely lytic phase. The osteolytic phase evolves into one marked by both osteoclastic and osteoblastic overactivity. This mixed phase is followed by a phase characterized by less active bone remodeling and marked sclerosis. In this final phase, excessive osteoblastic bone deposition predominates. Most patients who come to medical attention exhibit findings compatible with this phase.
6. Describe the radiographic findings associated with the osteolytic phase of Paget’s disease.
The characteristic radiographic finding in patients in the initial osteolytic phase of Paget’s disease of bone is an advancing wedge-shaped resorption front at either end of long tubular bones. In the skull, this phase is manifested by large circumscribed osteolytic lesions (termed osteoporosis circumscripta).
7. What are the radiographic findings most commonly found in the osteoblastic phase of the disease?
Evolution of osteolytic lesions into the osteoblastic phase may require years or even decades, during which the affected bone may become sclerotic and enlarged and may demonstrate bowing deformities, incomplete transverse fractures (pseudofractures), and even complete fractures. When the skull is involved in the osteoblastic phase, thickening of the calvarium and a patchy increase in bone density may give the skull a “cotton-wool” appearance. In this phase, the sclerotic bone changes may be so extensive that they may be confused with metastatic disease. Both metastatic cancer and Paget’s disease are common in the elderly and may coexist in the same patient. Thus, clinicians caring for patients with Paget’s disease must be alert for evidence of metastatic disease to bone.
8. What is the best radiographic evaluation to determine the extent of Paget’s disease?
The metabolic activity of osteoblastic pagetic bone lesions is most easily assessed by radionuclide scanning because these lesions avidly take up the technetium-labeled bisphosphonate. Although bone scans are diagnostically less specific than radiographic studies, they identify approximately 15% to 30% of pagetic lesions not visualized on radiographs. Conversely, when radiographs demonstrate pagetic involvement but the serum alkaline phosphatase concentration is normal and the bone scan reveals little isotope uptake at those sites, the diagnosis of relatively inactive or “burned out” Paget’s disease is most likely. Predominantly lytic bone lesions (such as osteoporosis circumscripta) may not be detected on bone scan. Computed tomography (CT) and magnetic resonance imaging (MRI) add little to the workup of patients with uncomplicated Paget’s disease.
9. Which bones are involved in Paget’s disease?
