From the Guidelines
Elevated alkaline phosphatase (ALP) levels can be caused by various conditions, including liver diseases such as bile duct obstruction, hepatitis, and cirrhosis, as well as bone diseases like Paget's disease and bone metastases, and other conditions like pregnancy and certain cancers. The causes of elevated ALP can be broadly categorized into liver-related and non-liver related causes. Liver-related causes include cholestatic liver diseases, such as primary biliary cholangitis, primary sclerosing cholangitis, and intrahepatic or extrahepatic bile duct obstruction, as well as other liver conditions like hepatitis, cirrhosis, and liver cancer 1. Non-liver related causes include bone diseases like Paget's disease, bone metastases, and fracture healing, as well as other conditions like pregnancy, certain cancers, and hyperthyroidism.
Some of the key liver-related causes of elevated ALP include:
- Bile duct obstruction, which can be caused by gallstones, tumors, or other conditions
- Hepatitis, which can be caused by viral or autoimmune factors
- Cirrhosis, which can be caused by chronic liver damage
- Primary biliary cholangitis, a chronic liver disease characterized by inflammation and scarring of the bile ducts
- Primary sclerosing cholangitis, a chronic liver disease characterized by inflammation and scarring of the bile ducts
Non-liver related causes of elevated ALP include:
- Paget's disease, a bone disease characterized by abnormal bone growth and remodeling
- Bone metastases, which can occur in patients with cancer
- Fracture healing, which can cause elevated ALP levels due to increased bone turnover
- Pregnancy, which can cause elevated ALP levels due to increased bone turnover and placental production of ALP
- Certain cancers, such as osteosarcoma or chondrosarcoma, which can cause elevated ALP levels due to bone involvement
When evaluating a patient with elevated ALP, it is essential to consider the clinical context and perform further testing to determine the underlying cause. This may include measuring gamma-glutamyl transferase (GGT) to distinguish between liver and bone sources, imaging studies, or additional blood tests to identify the underlying condition requiring treatment 1.
From the Research
Causes of Elevated Alkaline Phosphatase (ALP)
The causes of elevated ALP levels can be varied and include:
- Underlying malignancy, with the most common being infiltrative intrahepatic malignancy, bony metastasis, and both hepatic and bone metastasis 2
- Bone disease, such as Paget's disease or bone metastasis from malignancy 2, 3
- Unsuspected parenchymal liver disease, such as liver metastases or primary liver cancer 2, 3
- Non-malignant infiltrative liver disease, such as sarcoid hepatitis or liver hemangiomas 3
- Sepsis, particularly gram-negative or gram-positive bacterial sepsis, or fungal sepsis 3
- Biliary obstruction, either malignant or benign, such as a common bile duct stone 3
- Acquired immunodeficiency syndrome (AIDS) and related infections, such as mycobacterium avium intracellulare (MAI) or cytomegalovirus infection 3
- High bone turnover, particularly in postmenopausal women with osteoporosis 4
- Liver disease, such as alcohol-induced hepatitis, which can cause a transient increase in serum ALP levels even in patients with hypophosphatasia 5
- Certain types of cancer, such as pancreatic, lung, or colorectal cancer, which can have abnormal ALP expression and activity 6
Specific Conditions Associated with Elevated ALP
Elevated ALP levels have been associated with specific conditions, including:
- Metastatic intrahepatic malignancy, which is a common cause of isolated elevated ALP 2
- Bone metastasis from malignancy, which can cause extremely high levels of ALP 3
- Sepsis, which can cause an extremely high ALP level even with a normal bilirubin 3
- AIDS, which can cause elevated ALP levels due to related infections or conditions 3
- Osteoporosis, particularly in postmenopausal women, which can cause elevated ALP levels due to high bone turnover 4
- Hypophosphatasia, a rare inherited disorder that can cause low serum ALP levels, but can also have elevated ALP levels due to concomitant liver disease 5
- Certain types of cancer, which can have abnormal ALP expression and activity, and may use ALP as a potential tumor biomarker 6