From the Guidelines
Alkaline phosphatase (ALP) enzyme elevation is primarily caused by liver or bone disorders, with the most common liver-related causes including biliary obstruction, cholestatic liver diseases, hepatitis, liver cirrhosis, and infiltrative liver diseases, as well as bone-related causes such as Paget's disease, osteomalacia, and bone metastases, as noted in the most recent study 1. The causes of ALP elevation can be broadly categorized into liver-related and bone-related disorders. Liver-related causes include:
- Biliary obstruction (such as gallstones, bile duct strictures, or tumors)
- Cholestatic liver diseases (primary biliary cholangitis, primary sclerosing cholangitis)
- Hepatitis
- Liver cirrhosis
- Infiltrative liver diseases Bone-related causes include:
- Paget's disease
- Osteomalacia
- Rickets
- Bone metastases
- Fracture healing
- High bone turnover states Other significant causes of ALP elevation include:
- Pregnancy (due to placental production)
- Certain medications (like phenytoin, carbamazepine, and some antibiotics)
- Hyperthyroidism
- Sepsis
- Inflammatory bowel diseases As noted in 1, some individuals may have benign familial elevations of ALP. When evaluating elevated ALP, it's essential to determine the source by checking gamma-glutamyl transferase (GGT) or other liver enzymes, as concurrent elevation suggests liver origin, while normal liver enzymes with high ALP may indicate bone pathology, as discussed in 1. The degree of elevation can provide clues to the underlying cause, with marked elevations (more than three times normal) typically seen in biliary obstruction or infiltrative diseases. In clinical practice, it is crucial to consider the patient's clinical history, medications, and laboratory results to determine the underlying cause of ALP elevation, as emphasized in the most recent study 1.
From the Research
Causes of Alkaline Phosphatase (ALP) Elevation
The causes of ALP elevation can be attributed to various factors, including:
- Hepatobiliary diseases, such as cholestatic disease 2, 3, 4, 5, 6
- Bone diseases, such as those with increased osteoblastic activity 3, 4, 5, 6
- Malignancies, including infiltrative intrahepatic malignancy and bony metastasis 3
- Intestinal and placental origins 2
- Physiologic or spurious causes, such as young age, pregnancy, lactation, and high fat diets 4, 5
- Endocrine diseases, neoplasia, and other disorders 4, 5
- Induction by certain drugs, such as glucocorticoids and anticonvulsants 4
- Benign familial intestinal hyperphosphatasemia (BFIH) 2
- Unsuspected parenchymal liver disease and non-malignant infiltrative liver disease 3
Specific Causes and Their Frequencies
According to a study, the most common cause of ALP elevation was underlying malignancy (57%), followed by bone disease (29%), unsuspected parenchymal liver disease (7%), non-malignant infiltrative liver disease (2%), and other disorders (5%) 3.
Diagnostic Considerations
To determine the cause of ALP elevation, it is essential to consider the patient's clinical presentation, medical history, and other laboratory test results, such as gamma-glutamyl transpeptidase and serum alkaline phosphatase isozyme patterns 3, 4, 6.