From the Guidelines
Chronic elevation of alkaline phosphatase (ALP) is most commonly caused by cholestatic liver diseases, bone disorders, or other conditions affecting the liver, bones, or other organs, and the most recent evidence suggests that checking gamma-glutamyl transferase (GGT) levels is crucial in determining the origin of elevated ALP 1.
Causes of Chronic ALP Elevation
- Hepatic causes: cholestatic liver diseases such as primary biliary cholangitis, primary sclerosing cholangitis, drug-induced liver injury, and biliary obstruction from gallstones or tumors
- Bone-related causes: Paget's disease, osteomalacia, hyperparathyroidism, bone metastases, and healing fractures
- Other causes: pregnancy (placental production), certain medications like phenytoin and phenobarbital, inflammatory bowel disease, and some cancers that produce ALP isoenzymes
- Rare causes: familial benign hyperphosphatasemia, a harmless genetic condition
Diagnostic Approach
- Check GGT levels to determine the origin of elevated ALP, as concurrent elevation suggests liver origin, while normal GGT with high ALP points to bone sources 1
- Additional testing may include liver function tests, bone-specific ALP isoenzymes, vitamin D levels, parathyroid hormone measurement, and imaging studies of the liver, biliary tract, or bones depending on the clinical context
- Magnetic resonance cholangiopancreaticography (MRCP) is a preferred diagnostic test for large duct primary sclerosing cholangitis (PSC) 1
Recent Evidence
- A 2023 study published in the Journal of the American College of Radiology emphasizes the importance of checking GGT levels in determining the origin of elevated ALP 1
- A 2022 study published in the Journal of Hepatology provides recommendations for the diagnosis and management of sclerosing cholangitis, including the use of MRCP as a diagnostic test 1
From the Research
Causes of Chronic Alk Phos Elevation
- Paget's disease of bone (PDB) is a common cause of chronic alkaline phosphatase (ALP) elevation, characterized by disorganized bone remodeling and enhanced bone resorption 2, 3, 4.
- Defective elimination of ALP from the serum can also contribute to unexplained elevations of serum ALP 5.
- Bone disease, such as osteomalacia, can also lead to increased ALP activity 2, 6.
- Other disorders, including endocrine disease, neoplasia, and certain drug inductions (e.g., glucocorticoids and anticonvulsants), can also result in increased ALP activity 6.
- Physiologic changes, such as those occurring in young animals, pregnant and lactating females, and individuals with high fat diets, can also lead to non-hepatic increases in serum ALP activity 6.
Associated Conditions
- Secondary hyperparathyroidism can occur in patients with PDB, particularly after treatment with bisphosphonates, and may be a potentially detrimental condition 2.
- Hypocalcemia and mineralization defects have also been described in patients with PDB treated with bisphosphonates 2, 3.