Can fibrous dysplasia cause elevated alkaline phosphatase levels?

Fibrous Dysplasia and Elevated Alkaline Phosphatase

Yes, fibrous dysplasia can cause elevated alkaline phosphatase levels due to increased bone turnover associated with the disease. 1, 2

Pathophysiology and Laboratory Findings

• Fibrous dysplasia is characterized by abnormal bone formation where normal bone is replaced by fibrous tissue, leading to increased bone turnover that elevates alkaline phosphatase (ALP) levels 1, 2
• Bone-specific alkaline phosphatase is particularly elevated in fibrous dysplasia, reflecting the high bone turnover state associated with the disease 2, 3
• In polyostotic fibrous dysplasia (affecting multiple bones), ALP elevation correlates positively with the number of affected bones 2
• Studies have shown that serum ALP levels can be significantly elevated (>250 U/L) for several years in patients with fibrous dysplasia 4

Differential Diagnosis

When evaluating elevated alkaline phosphatase in the context of bone disorders:

• Fibrous dysplasia should be distinguished from other conditions that cause elevated ALP, such as:

  • Paget's disease - typically affects older adults and has characteristic radiographic findings 1, 4
  • Osteomalacia - associated with vitamin D deficiency, hypocalcemia, or hypophosphatemia 1
  • Hyperparathyroidism - characterized by elevated PTH levels 1
  • Bone metastases - more common in older adults with known malignancy 1

• In fibrous dysplasia with elevated FGF23 (fibroblast growth factor 23), hypophosphatemia may also be present, further distinguishing it from other bone disorders 1, 3

Diagnostic Approach

• Radiographic imaging is essential for diagnosis, showing characteristic "ground-glass" lesions on X-ray or CT 1

• Bone scintigraphy can help determine the extent of skeletal involvement 4

• Laboratory evaluation should include:

  • Total and bone-specific alkaline phosphatase 1, 2
  • Calcium, phosphate, and PTH levels to rule out other metabolic bone disorders 1
  • Markers of bone turnover such as urinary collagen type I N-telopeptide may also be elevated 5

• Bone biopsy remains the gold standard for definitive diagnosis, showing replacement of normal bone by fibrous tissue 1, 4

Clinical Significance and Monitoring

• Elevated ALP in fibrous dysplasia can serve as a biomarker for disease activity and extent 2, 3
• ALP levels can be used to monitor response to treatment with bisphosphonates, with studies showing 22-34% reduction in ALP within the first year of therapy 2
• Persistent elevation of ALP in adults with fibrous dysplasia may be associated with increased risk of malignant transformation, though this is rare 6
• Regular monitoring of ALP levels is recommended for patients with fibrous dysplasia to assess disease activity and treatment response 2, 5

Treatment Considerations

• Bisphosphonate therapy (pamidronate, zoledronic acid, alendronate) can reduce elevated ALP levels by suppressing the high bone turnover associated with fibrous dysplasia 2, 5
• Treatment efficacy can be monitored through serial measurements of ALP and other bone turnover markers 2, 5
• The degree of ALP elevation at baseline may predict response to bisphosphonate therapy 2

In summary, elevated alkaline phosphatase is a common finding in fibrous dysplasia due to increased bone turnover, and its measurement is valuable for diagnosis, monitoring disease activity, and assessing treatment response.