From the Guidelines
Elevated alkaline phosphatase (ALP) levels are primarily caused by liver diseases, such as cholestatic liver disease, cirrhosis, and hepatitis, as well as bone diseases like Paget's disease and fractures, according to 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 and primary sclerosing cholangitis
- Cirrhosis and chronic hepatitis
- Viral hepatitis and congestive heart failure (hepatic congestion)
- Intrahepatic or extrahepatic bile duct obstruction and drug-induced cholestasis
- Non-hepatic causes include:
- Bone diseases, such as Paget's disease, bony metastases, and fractures
- Physiologically higher levels in childhood and pregnancy due to bone growth and placental production, respectively To determine the origin of elevated ALP, measurements of gamma-glutamyl transpeptidase (GGT) can be helpful, as concomitantly elevated GGT suggests a hepatic origin 1. In cases where the liver is suspected to be the source of elevated ALP, imaging of the biliary tree may be necessary to determine the etiology of extrahepatic or intrahepatic cholestasis, with choledocholithiasis being the most common cause of extrahepatic biliary obstruction 1.
From the FDA Drug Label
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, which leads to increased bone formation and elevated ALP levels
- Disorderly bone formation, which can result in elevated ALP levels due to the increased bone turnover 2
From the Research
Causes of Elevated Alkaline Phosphatase (ALP) Levels
Elevated ALP levels can be caused by various factors, including:
- Underlying malignancy, with 57% of cases attributed to this cause, including infiltrative intrahepatic malignancy, bony metastasis, and both hepatic and bone metastasis 3
- Bone disease, accounting for 29% of cases 3
- Unsuspected parenchymal liver disease, accounting for 7% of cases 3
- Non-malignant infiltrative liver disease, accounting for 2% of cases 3
- Other disorders, accounting for 5% of cases 3
- High bone turnover, particularly in postmenopausal women 4
- Congestive hepatopathy in the setting of heart failure with preserved ejection fraction (HFpEF) 5
- Benign transient hyperphosphatasemia (TH) following adult renal transplantation, characterized by a temporary and severe elevation of ALP levels without evidence of liver or bone disease 6
- Intestinal and placental sources of ALP, although these are less common causes of elevated ALP levels 7
Specific Causes and Associations
Some specific causes and associations of elevated ALP levels include:
- Metastatic intrahepatic malignancy, which is a common cause of isolated elevated ALP 3
- Osteoporosis, where ALP is an acceptable alternative to bone-specific alkaline phosphatase (BAP) for monitoring bone turnover 4
- Heart failure with preserved ejection fraction (HFpEF), where congestive hepatopathy can cause significantly elevated ALP levels 5
- Renal transplantation, where benign transient hyperphosphatasemia (TH) can occur, characterized by a temporary and severe elevation of ALP levels without evidence of liver or bone disease 6