From the Guidelines
Elevated alkaline phosphatase (ALP) levels most commonly result from liver disease or bone disorders, with bile duct obstruction (cholestasis) being a primary cause in liver conditions, as supported by the most recent study 1. The causes of elevated ALP levels can be broadly categorized into liver and bone disorders. In liver conditions, cholestasis is a primary cause, whether from gallstones, tumors, or primary biliary cholangitis. Other hepatic causes include viral hepatitis, alcoholic liver disease, and drug-induced liver injury. For bone-related elevations, Paget's disease, osteomalacia, hyperparathyroidism, and bone metastases are frequent culprits. Some key points to consider when evaluating elevated ALP levels include:
- Growing children naturally have higher ALP levels due to bone formation, as noted in 1.
- Pregnancy can cause physiologic elevation, particularly in the third trimester.
- Other causes include certain cancers (especially with metastases), inflammatory bowel disease, sepsis, and hyperthyroidism.
- Some medications like certain antibiotics and anti-seizure drugs can also increase ALP. When evaluating elevated ALP, it's essential to check other liver enzymes and consider isoenzyme testing to determine if the source is hepatic or bone-related, as this distinction guides further diagnostic workup and treatment, as recommended in 1 and 1. The most common causes of elevated ALP levels can be remembered by considering the following:
- Liver diseases: cholestasis, viral hepatitis, alcoholic liver disease, and drug-induced liver injury.
- Bone disorders: Paget's disease, osteomalacia, hyperparathyroidism, and bone metastases.
- Other causes: growing children, pregnancy, certain cancers, inflammatory bowel disease, sepsis, hyperthyroidism, and certain medications. It's crucial to approach elevated ALP levels with a comprehensive evaluation, including a review of the patient's clinical history, medications, and laboratory tests, to determine the underlying cause and guide appropriate treatment, as emphasized in the most recent study 1.
From the Research
Causes of Elevated Alkaline Phosphatase (ALP) Levels
Elevated ALP levels can be caused by various factors, including:
- Hepatobiliary diseases 2
- Bone diseases, such as Paget's disease of bone (PDB) 3, 4
- Intestinal and placental sources of ALP 2, 5
- Benign familial intestinal hyperphosphatasemia (BFIH) 2
- Transient hyperphosphatasemia (TH) in adults following renal transplantation 6
- Certain types of cancer, including liver and bone metastasis, pancreatic and lung cancer 5
Disease-Specific Causes
- Paget's disease of bone (PDB) is characterized by disorganized bone remodeling, and elevated serum ALP levels correlate with disease activity 3, 4
- Transient hyperphosphatasemia (TH) in adults following renal transplantation is a benign condition with isolated ALP serum levels returning to normal limits within 12 weeks 6
- Cancer-related ALP elevation can be observed in patients with liver and bone metastasis, pancreatic and lung cancer, while low ALP expression is associated with poor prognosis in certain types of tumors, including colorectal cancer, breast cancer, and non-small cell lung cancer 5