Alkaline Phosphatase is Elevated in Paget's Disease
Serum alkaline phosphatase (ALP) is the laboratory marker that is characteristically elevated in Paget's disease of bone, often reaching levels 2-10 times the upper limit of normal, and serves as both a diagnostic clue and a marker of disease activity. 1, 2, 3, 4, 5, 6, 7, 8
Diagnostic Laboratory Findings
Alkaline phosphatase elevation:
- ALP is elevated in essentially all patients with active Paget's disease, reflecting increased osteoblastic activity and accelerated bone formation 5, 6, 7, 8
- The degree of elevation correlates with disease activity and extent of skeletal involvement 5, 7
- Levels can range from mildly elevated to >10 times the upper limit of normal, with average values around 618 ± 460 IU/L reported in case series 8
- Treatment is indicated when ALP is elevated to two times or higher than the upper limit of the age-specific normal reference range 3
Other laboratory parameters:
- Serum calcium and phosphorus levels typically remain normal in Paget's disease, which helps distinguish it from other metabolic bone disorders 5, 8
- Urine hydroxyproline excretion may be elevated, reflecting increased bone resorption 4
- Bone-specific alkaline phosphatase can be measured for greater specificity when total ALP is equivocal 2
Differential Diagnosis Considerations
When evaluating elevated ALP, Paget's disease should be considered alongside other causes 1, 2:
Key distinguishing features of Paget's disease:
- Family history of Paget's disease 1
- Pelvic or skull localization of bone lesions 1
- Characteristic mixed osteolytic and osteosclerotic appearance on imaging 1
- Age of onset usually >50 years (though younger cases occur) 1, 6
- Bone deformities may be present 1, 7
Other metabolic bone diseases to exclude:
- Osteomalacia: presents with low serum phosphate, elevated ALP, low 25-hydroxy-vitamin D, increased parathyroid hormone, and bone demineralization 1
- Hypophosphatasia: presents with low alkaline phosphatase levels (opposite of Paget's), bone demineralization, and mixed lytic/sclerotic lesions 1
Diagnostic Confirmation
After identifying elevated ALP, confirm Paget's disease with:
- Plain radiography showing characteristic features (mixed lytic/sclerotic lesions, cortical thickening, bone expansion) 6, 7
- Radionuclide bone scan (99mTc-methylene diphosphonate) to assess extent of disease—this is the most sensitive test 5, 7, 8
- Bone biopsy is rarely needed but shows mosaic pattern of bone trabeculae with irregular cement lines and multinuclear osteoclasts 8
Monitoring Treatment Response
ALP serves as the primary marker for treatment response:
- Measure total serum ALP at 3-6 months after initiating bisphosphonate therapy to evaluate response 7
- Successful treatment with zoledronic acid or other bisphosphonates leads to sustained reduction in ALP levels 4, 6
- Re-treatment may be considered if ALP increases again after initial normalization, indicating disease relapse 3
Clinical Pitfall to Avoid
Do not assume all elevated ALP is hepatobiliary in origin—always measure GGT concurrently to confirm hepatic source, as normal GGT with elevated ALP suggests bone origin including Paget's disease 2. In patients over 50 years with unexplained ALP elevation and normal GGT, obtain plain radiographs of commonly affected sites (pelvis, spine, skull, long bones) to evaluate for Paget's disease 6, 7.