What is Alkaline Phosphatase?
Alkaline phosphatase (ALP) is a group of enzymes that catalyze the hydrolysis of phosphate esters at an alkaline pH, producing inorganic phosphate, and is widely distributed across multiple tissues including bone, liver, intestine, and placenta. 1, 2
Biochemical Function and Distribution
ALP represents one of the most frequently measured enzymes in clinical medicine, with its activity found predominantly in bone, liver, intestinal, and placental tissues. 2 The enzyme functions by breaking down phosphate-containing compounds under alkaline conditions, releasing inorganic phosphate in the process. 1
Clinical Significance as a Biomarker
Tissue-Specific Isoenzymes
The enzyme exists as distinct isoforms after posttranslational modifications, with tissue-nonspecific alkaline phosphatase (TNALP) being one of four human isozymes. 3 The bone-specific isoforms (B/I, B1, B1x, and B2) are particularly important for bone mineralization and are involved in various pathological processes including ectopic calcification. 3
Markers of Bone and Liver Disease
- Bone-specific alkaline phosphatase (B-ALP or BAP) reflects ongoing rates of osteogenesis and bone formation, serving as a sensitive marker for bone turnover and bone metastases. 4
- Elevated serum ALP is universally recognized as a marker for skeletal or hepatobiliary disease, though the assay conditions are somewhat nonphysiological. 2
- Bone ALP is the classic marker of bone formation, especially in cancer patients, though interpretation is complicated by circulating isoenzymes of liver origin. 5
Biochemical Markers of Bone Metabolism
Serum levels of bone-specific alkaline phosphatase reflect ongoing rates of osteogenesis, while other markers like CTX and NTX reflect osteolysis. 4 These markers provide insight into skeletal metabolism and tumor-bone interactions in patients with malignant bone disease, though they reflect whole-body bone turnover rather than individual lesion sites. 4
Diagnostic Applications
Hepatobiliary Disease
Cholestatic liver diseases including primary biliary cholangitis, primary sclerosing cholangitis, drug-induced cholestasis, and bile duct obstruction are major causes of chronic ALP elevation. 6 Measuring gamma-glutamyl transferase (GGT) alongside ALP helps confirm hepatobiliary origin—elevated GGT confirms hepatic source while normal GGT suggests bone origin. 6
Bone Disease
- Metabolic bone disorders including Paget's disease, bone metastases, and fractures cause significant ALP elevation. 6
- Physiologic elevations occur during childhood due to bone growth and in pregnancy due to placental production. 6
- In chronic kidney disease, elevated B-ALP is predominantly driven by secondary hyperparathyroidism and altered bone metabolism. 7
Cancer Applications
Elevated serum ALP levels are observed in patients with liver and bone metastases, as well as in pancreatic and lung cancer. 1 BAP levels correlate with the extent of bone metastatic involvement better than total ALP or other bone markers. 5 Combined detection of ALP with other markers (AST/ALT, CA 19-9, LDH) can improve diagnostic accuracy for specific tumors. 1
Clinical Interpretation Considerations
The term "alkaline phosphatase" emerged when it became necessary to distinguish "bone phosphatase" from prostatic phosphatase, which has an acidic pH optimum. 2 Analysis of ALP isoenzymes aids in diagnosing liver versus bone disease, particularly the high molecular weight isoenzymes appearing in cholestatic liver disease. 8