From the Guidelines
Alkaline phosphatase (ALP) is a crucial enzyme found in various tissues, including the liver, bones, intestines, and placenta, and its levels are commonly measured to assess liver and bone health, with elevated levels potentially indicating conditions such as liver disorders or bone diseases 1. In clinical settings, ALP is an essential marker for diagnosing and monitoring various conditions.
- It is produced mainly in the liver and is present in the canalicular membrane of the hepatocyte, with smaller amounts found in bone, intestines, kidneys, and white blood cells.
- Physiologically, ALP levels are higher in childhood due to bone growth and in pregnancy due to placental production.
- Elevated ALP levels can occur in a variety of conditions, including liver diseases such as cirrhosis, chronic hepatitis, and cholestatic liver disease, as well as bone diseases like Paget’s disease and bony metastases.
- Measurements of gamma-glutamyl transpeptidase (GGT) can help determine whether elevated ALP is of hepatic or nonhepatic origin, as GGT is found in the liver and kidneys but not in bone 1.
- Concomitantly elevated GGT can confirm that an elevated ALP originates from the liver, indicating cholestasis, and may necessitate imaging of the biliary tree to determine the etiology of extrahepatic or intrahepatic cholestasis.
- Isolated elevated ALP of hepatic origin can suggest a chronic cholestatic process, such as partial bile duct obstruction or primary biliary cholangitis, while nonspecific elevations can occur in various liver diseases, including hepatitis, cirrhosis, and heart failure 1.
From the Research
Definition and Overview of Alkaline Phosphatase
- Alkaline phosphatase (ALP) is an enzyme that catalyzes the hydrolysis of phosphate monoesters at basic pH values 2.
- It is a ubiquitous membrane-bound glycoprotein found in many mammalian tissues, including bone, liver, and kidney 2.
- ALP is divided into four isozymes depending on the site of tissue expression: Intestinal ALP, Placental ALP, Germ cell ALP, and tissue nonspecific alkaline phosphatase or liver/bone/kidney (L/B/K) ALP 2.
Physiological Role of Alkaline Phosphatase
- The bone isoenzyme of ALP may be involved in mammalian bone calcification 2.
- The intestinal isoenzyme is thought to play a role in the transport of phosphate into epithelial cells of the intestine 2.
- ALP is also involved in the pathogenesis of ectopic calcification, inflammation, metabolic syndrome, vascular calcification, endothelial dysfunction, fibrosis, cardiovascular disease, and mortality 3.
Clinical Significance of Alkaline Phosphatase
- Elevated activity of ALP in the circulation is universally recognized as a marker for skeletal or hepatobiliary disease 4.
- ALP is widely used as a biomarker in clinical practice, particularly in the diagnosis and treatment of metabolic bone diseases 4.
- Bone-specific alkaline phosphatase (B-ALP) is an isoform of ALP found in bone tissue, which can predict fractures and heterotopic ossification 5.
Research and Studies on Alkaline Phosphatase
- Studies have explored the use of ALP as a bone turnover marker after spinal cord injury, with conflicting evidence regarding changes or differences in ALP levels in individuals with SCI compared to controls 5.
- Research has also investigated the role of ALP in pathological mineralization, such as dystrophic and vascular calcification, and its potential contribution to human tissue aging 6.
- Recent advances in pharmacological strategies have highlighted the potential to modulate the expression of ALP directly and indirectly in chronic kidney disease-mineral and bone disorder (CKD-MBD) 3.