From the Guidelines
Elevated alkaline phosphatase (ALP) levels can be caused by a variety of conditions, including liver disorders, bone diseases, and other factors, and require further investigation to determine the underlying cause, as suggested by the most recent study 1. The causes of elevated ALP levels can be broadly categorized into hepatic and non-hepatic origins. Hepatic causes include cholestatic liver disease, such as primary biliary cholangitis, primary sclerosing cholangitis, intrahepatic or extrahepatic bile duct obstruction, and drug-induced cholestasis, as well as other liver conditions like cirrhosis, chronic hepatitis, and viral hepatitis 1.
- Common hepatic causes of elevated ALP include:
- Cholestatic liver disease
- Intrahepatic or extrahepatic bile duct obstruction
- Drug-induced cholestasis
- Cirrhosis
- Chronic hepatitis
- Viral hepatitis Non-hepatic causes of elevated ALP include bone diseases like Paget’s disease, bony metastases, or fracture, as well as other conditions such as pregnancy and certain medications 1.
- Common non-hepatic causes of elevated ALP include:
- Bone diseases (Paget’s disease, bony metastases, or fracture)
- Pregnancy
- Certain medications To determine the underlying cause of elevated ALP, additional tests and imaging studies may be necessary, such as measurements of gamma-glutamyl transpeptidase (GGT) to indicate whether the elevated ALP is of hepatic or non-hepatic origin, and imaging of the biliary tree to determine the etiology of extrahepatic or intrahepatic cholestasis 1. The most appropriate next step in evaluating elevated ALP levels is to conduct a comprehensive medical history, physical examination, and additional blood tests to check liver function and determine the origin of the ALP elevation, as recommended by the latest guidelines 1.
From the FDA Drug Label
Serum alkaline phosphatase, the most frequently used biochemical index of disease activity, provides an objective measure of disease severity and response to therapy. Paget's disease of bone is a chronic, focal skeletal disorder characterized by greatly increased and disorderly bone remodeling Excessive osteoclastic bone resorption is followed by osteoblastic new bone formation, leading to the replacement of the normal bone architecture by disorganized, enlarged, and weakened bone structure.
The causes of elevated alkaline phosphatase (ALP) levels include:
- Paget's disease of bone, a chronic skeletal disorder characterized by increased and disorderly bone remodeling
- Excessive osteoclastic bone resorption followed by osteoblastic new bone formation
- Disorderly bone formation, leading to the replacement of normal bone architecture by disorganized, enlarged, and weakened bone structure 2
From the Research
Causes of Elevated Alkaline Phosphatase (ALP) Levels
Elevated ALP levels can be caused by a variety of factors, including:
- Bone involvement from malignancy or Paget's disease 3
- Sepsis, including gram-negative and gram-positive organisms, as well as fungal sepsis 3, 4
- Biliary obstruction, including malignant obstruction and common bile duct stones 3
- Acquired immunodeficiency syndrome (AIDS) 3
- Diffuse liver metastases 3
- Benign intrahepatic disease, including liver hemangiomas, sarcoid hepatitis, lead toxicity, and drug-induced cholestasis 3
- Underlying malignancy, including infiltrative intrahepatic malignancy, bony metastasis, and both hepatic and bone metastasis 5
- Bone disease, including osteomalacia and Paget's disease 5, 6
- Unsuspected parenchymal liver disease, including hepatitis and cirrhosis 5
- Non-malignant infiltrative liver disease, including sarcoidosis and amyloidosis 5
- Other disorders, including hyperthyroidism and hypothyroidism 6
- Certain drugs, including glucocorticoids and anticonvulsants 6
- Bacteremia, including gram-negative and gram-positive organisms 4
- Tumors, including liver, bone, pancreatic, and lung cancer 7
Specific Causes of Elevated ALP Levels
Some specific causes of elevated ALP levels include:
- Malignant obstruction, which can cause extremely high elevations of ALP 3
- Sepsis, which can cause extremely high elevations of ALP, even in the absence of jaundice 3, 4
- AIDS, which can cause elevated ALP levels due to a variety of opportunistic infections and malignancies 3
- Bone metastasis, which can cause elevated ALP levels due to increased bone turnover 5, 7
- Liver metastasis, which can cause elevated ALP levels due to increased liver enzyme production 5, 7
Clinical Significance of Elevated ALP Levels
Elevated ALP levels can have significant clinical implications, including: