From the Guidelines
The evaluation and management of elevated alkaline phosphatase (ALP) should begin with a systematic approach to determine the source of elevation, considering the most recent evidence from 2024 1.
Key Steps in Evaluation
- Confirm whether the elevation is isolated or accompanied by other liver enzyme abnormalities.
- Order fractionation of ALP to distinguish between liver, bone, intestinal, or placental origins.
- For suspected hepatobiliary causes, obtain imaging studies such as ultrasound, CT, or MRCP to evaluate for biliary obstruction, infiltrative diseases, or mass lesions, as recommended by the American College of Radiology in 2023 1.
- Additional laboratory tests should include gamma-glutamyl transferase (GGT), bilirubin, transaminases, and tests for viral hepatitis, autoimmune markers (ANA, ASMA, AMA), and iron studies.
Bone-Origin ALP Elevations
- For bone-origin ALP elevations, check calcium, phosphate, parathyroid hormone, and vitamin D levels, and consider bone imaging, taking into account the findings from the Kidney Disease: Improving Global Outcomes (KDIGO) controversies conference in 2025 1.
Management
- Management depends on the underlying cause:
- Treat biliary obstruction with ERCP or surgery.
- Address autoimmune hepatitis with prednisone (starting at 40-60mg daily with gradual taper) and azathioprine (1-2mg/kg/day).
- Manage primary biliary cholangitis with ursodeoxycholic acid (13-15mg/kg/day).
- Treat bone disorders with specific therapies like bisphosphonates for Paget's disease.
Monitoring
- Regular monitoring of ALP levels is essential to assess treatment response, with frequency determined by the underlying condition and severity of elevation, and considering the recommendations for detection, assessment, and management of suspected drug-induced liver injury during clinical trials in oncology patients from 2024 1.
Individualized Approach
- The approach must be individualized, as ALP elevations reflect diverse pathologies affecting multiple organ systems, and should be guided by the most recent and highest quality evidence available, such as the study published in the Journal of the American College of Radiology in 2023 1.
From the Research
Approach to Evaluating Elevated Alkaline Phosphatase (ALP) Levels
Elevated ALP levels can be indicative of various diseases, most commonly affecting the skeleton and the biliary tract 2. The approach to evaluating and managing a patient with elevated ALP levels involves:
- Measuring total ALP activity in serum or plasma as a useful biomarker in clinical practice 2
- Using electrophoretic assays to visualize and investigate the cause of increased serum total ALP activities 2
- Utilizing bone ALP immunoassays to investigate and monitor individuals with bone and mineral metabolic abnormalities 2
Differential Diagnosis
The differential diagnosis of elevated ALP levels includes:
- Bone diseases, such as osteomalacia, rickets, and Paget's disease 2
- Liver diseases, such as hepatitis, cirrhosis, and cholestasis 2
- Other conditions, such as hypophosphatasia, a rare genetic disorder characterized by low ALP activity 2
Bone-Specific Alkaline Phosphatase (B-ALP)
B-ALP is an isoform of ALP found in bone tissue and can be used as a biomarker for bone turnover and osseous metastases 3, 4. The use of B-ALP as a biomarker has been explored in various studies, including:
- A scoping review of human and animal studies on the use of ALP and B-ALP as a bone marker after spinal cord injury 3
- A systematic review and meta-analysis on the use of serum B-ALP as a biomarker for osseous metastases in patients with malignant carcinomas 4
Clinical Applications
The clinical applications of ALP and B-ALP include:
- Diagnosis and monitoring of bone and mineral metabolic disorders, such as chronic kidney disease-mineral and bone disorder (CKD-MBD) 5
- Evaluation of the growth hormone/insulin-like growth factor-1 axis and vitamin D status in children with growth hormone deficiency 6
- Prediction of fractures and heterotopic ossification in patients with spinal cord injury 3