High-Yield Exam Information for Paget's Disease of Bone
Clinical Presentation & Epidemiology
Paget's disease of bone (PDB) is a chronic focal disorder of bone metabolism affecting 1-2% of the population, typically those over age 55 years, and is usually asymptomatic. 1
- Most cases are discovered incidentally through elevated serum alkaline phosphatase or abnormal radiographs 1, 2
- When symptomatic, patients present with bone pain, bone deformity, pathological fractures, secondary osteoarthritis, and deafness 3
- Bone pain may show increased warmth over affected areas 2
- Complications include spinal cord compression and nerve compression syndromes 3
Differential Diagnosis
The differential diagnosis includes osteoporosis, degenerative disease, metastatic bone disease, and osteosarcoma (which can develop as a secondary malignancy in adults >65 years with Paget's disease). 4
- Other considerations: fibrous dysplasia, hypophosphatasia, osteomalacia 4
- In adults >40 years, metastatic carcinoma to bone is more likely and should be excluded 4
Diagnostic Workup
Laboratory Tests
Serum total alkaline phosphatase (ALP) is the primary biochemical screening test and must be measured with liver function tests to exclude hepatic causes of elevated ALP. 5, 6
- Additional tests: calcium, 25-hydroxy-vitamin D, phosphate, and parathyroid hormone to exclude other metabolic bone diseases 5, 6
- More specific bone turnover markers (PINP or CTX) can be used for additional confirmation 5
Imaging
Plain radiographs of suspected skeletal regions are the first-line investigation, showing characteristic mixed osteolytic and osteosclerotic appearance. 5
- Radionuclide bone scintigraphy should be performed to determine the full extent of skeletal involvement 5, 7
- CT and MRI provide structural information but are not first-line 4
- Isotope bone scanning is sensitive for detecting skeletal pathology but gives little information about its nature 4
Treatment
Indications for Treatment
Treatment is mandatory for all symptomatic cases at diagnosis with bisphosphonates. 8
- Asymptomatic patients should be treated if the pagetic lesion is located where progression to fracture, deformity, or compression would significantly impair quality of life 2
- Caution: Treatment of asymptomatic PDB with bisphosphonates has been associated with increased fracture rates 1
Bisphosphonate Therapy
A single 5 mg intravenous dose of zoledronic acid is the current standard therapy, leading to sustained reduction in bone pain and markers of bone turnover. 1, 7
- Zoledronic acid is the most effective bisphosphonate for PDB 1, 2
- Alternative oral agents: alendronate, risedronate (both contraindicated if GFR <30-35 mL/min/1.73 m²) 9
- Pamidronate has sustained effects for months following a single injection 9
- Prior diphosphonate use reduces the anti-resorptive response to subsequent treatment 10
Critical Pre-Treatment Requirements
Calcium and vitamin D sufficiency must be ensured before and during bisphosphonate treatment to prevent hypocalcemia. 2
Alternative Therapy
- Calcitonin inhibits osteoclast function and can be used, though bisphosphonates are preferred 10, 3
- Analgesics and anti-inflammatory agents are often needed for pain from complications like osteoarthritis and nerve compression, which do not respond to antiresorptive therapy 3
Key Pitfalls
- Pain in Paget's disease can arise from multiple sources (increased bone turnover, osteoarthritis, nerve compression), not all of which respond to antiresorptive therapy 3
- No current treatments have been proven to prevent complications such as deafness, fracture, or bone deformity 3
- Skeletal radiography for monitoring response is delayed and insensitive 4
- Isotopic bone scanning is not useful for monitoring treatment response 4