From the Guidelines
Elevated alkaline phosphatase (ALP) can be caused by various conditions, including liver diseases such as cholestatic liver disease, cirrhosis, and hepatitis, as well as bone diseases like Paget's disease and fractures, as noted in a 2023 study 1. When considering the potential causes of elevated ALP, it is essential to recognize that 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 smaller amounts in the intestines, kidneys, and white blood cells 1. Some key causes of elevated ALP include:
- Cholestatic liver disease, such as primary biliary cholangitis and primary sclerosing cholangitis
- Intrahepatic or extrahepatic bile duct obstruction
- Drug-induced cholestasis
- Bone disease, such as Paget’s disease, bony metastases, or fracture
- Liver conditions like cirrhosis, chronic hepatitis, viral hepatitis, and congestive heart failure (hepatic congestion) To determine the underlying cause of elevated ALP, measurements of gamma-glutamyl transpeptidase (GGT) can be helpful, as concomitantly elevated GGT can indicate that the elevated ALP originates from the liver and suggests cholestasis 1. In clinical practice, a thorough review of the patient's clinical history, medications, and additional laboratory findings, such as liver function tests and imaging studies, is necessary to pinpoint the source of elevated ALP 1.
From the Research
Causes of Elevated Alkaline Phosphatase
- Paget's disease of bone, a common bone disorder characterized by disorganized bone remodeling, can cause an elevated serum alkaline phosphatase level, which correlates with the disease activity 2
- Osteomalacia, a condition caused by inadequate or delayed mineralization of bone, may also be associated with elevated alkaline phosphatase levels, although the exact relationship is not well-defined in the provided studies
- Vitamin D deficiency, which is common in patients with Paget's disease of bone, may contribute to elevated alkaline phosphatase levels, as adequate vitamin D status is essential for skeletal health 3
Associated Conditions
- Secondary hyperparathyroidism, which can occur in patients with Paget's disease of bone treated with bisphosphonates, may also be associated with elevated alkaline phosphatase levels 4
- Osteoporosis, although not directly linked to elevated alkaline phosphatase in the provided studies, is a common condition that can co-occur with Paget's disease of bone and osteomalacia 5
Biochemical Markers
- Serum total alkaline phosphatase (ALP) is recommended as a first-line biochemical screening test for Paget's disease of bone, in combination with liver function tests 6