From the Guidelines
Elevated alkaline phosphatase (ALP) levels can result from various conditions, including liver diseases such as biliary obstruction, hepatitis, and cirrhosis, as well as bone-related causes like Paget's disease and osteomalacia, and other conditions like pregnancy and intestinal diseases. The causes of elevated ALP levels can be broadly categorized into liver and non-liver related conditions. Liver causes include:
- Biliary obstruction (gallstones, tumors, primary biliary cholangitis)
- Hepatitis
- Cirrhosis
- Infiltrative diseases
- Medications like phenytoin and statins Non-liver causes include:
- Bone-related diseases such as Paget's disease, osteomalacia, hyperparathyroidism, bone metastases, healing fractures, and growing children
- Pregnancy (placental production)
- Intestinal diseases (inflammatory bowel disease, celiac disease)
- Hyperthyroidism
- Sepsis
- Certain cancers According to the most recent study 1, ALP is produced mainly in the liver and is present in the canalicular membrane of the hepatocyte, but it is also found in bone and in smaller amounts in the intestines, kidneys, and white blood cells. The pattern of elevation and accompanying symptoms help determine the source of elevated ALP levels. For example, isolated ALP elevation with bone pain suggests bone pathology, while elevation with jaundice points to liver disease. Gamma-glutamyl transferase (GGT) can help distinguish liver from bone sources, as it rises with liver but not bone disease, as noted in the study 1. Isoenzyme testing can further pinpoint the source organ. When investigating elevated ALP, clinicians typically order additional liver function tests, imaging studies, and sometimes bone markers to determine the underlying cause and appropriate treatment, as recommended in the study 1. It is essential to consider the clinical history and medications when evaluating elevated ALP levels, as certain medications like phenytoin and statins can cause elevated ALP levels, as mentioned in the study 1. In some cases, imaging of the biliary tree may be necessary to determine the etiology of extrahepatic or intrahepatic cholestasis, as suggested in the study 1. Overall, a comprehensive approach is necessary to determine the underlying cause of elevated ALP levels and provide appropriate treatment.
From the Research
Causes of Elevated Alkaline Phosphatase (ALP) Levels
- Underlying malignancy, including infiltrative intrahepatic malignancy, bony metastasis, and both hepatic and bone metastasis 2
- Bone disease, such as osteomalacia or Paget's disease 2, 3
- Unsuspected parenchymal liver disease, including cholestatic and non-cholestatic liver diseases 2, 4
- Non-malignant infiltrative liver disease, such as hepatic fibrosis or cirrhosis 2
- Other disorders, including hypophosphatasia, a rare inherited disorder caused by pathogenic loss-of-function variants in the ALPL gene 5
- Liver disease, including alcohol-induced hepatitis, which can cause a transient increase in serum ALP levels 5
- Idiopathic severe elevation of serum ALP, which can occur in adults following renal transplantation, characterized by a benign and transient condition with no evidence of liver or bone disease 6
- Nonhepatic increases in serum ALP activity, found in young animals, pregnant and lactating females, and in association with high fat diets 3
- Endocrine disease, neoplasia, and other disorders, which can result in increased alkaline phosphatase activity 3
- Induction by certain drugs, such as glucocorticoids and anticonvulsants, which can increase alkaline phosphatase activity 3