Brenda Spriggs, MD, MPH, MBA
Alkaline phosphatase, or ALP, is an enzyme that is responsible for cleaving phosphate groups from other molecules, such as nucleotides, which are building blocks for DNA, and proteins. This process is important for expediting the cellular absorption of complex molecules, regulating the activity of other enzymes and providing phosphate groups for various cellular functions. ALP is present in all human tissues, but its highest concentrations are found in the liver, bones, kidneys and placenta. Elevations in ALP occur in several situations.
ALP levels rise immediately after a fatty meal as the small intestine releases the enzyme into the bloodstream. Pregnancy usually prompts a rise in ALP due to placental production. Children and adolescents typically exhibit higher ALP levels during periods of rapid bone growth. These so-called physiologic elevations in ALP are normal and transient.
Liver disorders frequently cause ALP levels to rise. In fact, aside from physiologic causes, liver disease is probably the most common reason for ALP elevation. Bile duct obstruction, hepatitis, cirrhosis, fatty liver and liver cancer can all stimulate increases in ALP production.
ALP normally rises whenever bone is actively growing. Pathologic bone conditions that cause ALP to increase include fractures, primary bone tumors or invasion of bone by other cancers and disorders that increase bone turnover, such as hyperparathyroidism and Paget’s disease. In osteoporosis, where bone is being absorbed faster than it is produced, ALP is typically normal unless a recent fracture has occurred.
Physicians have long recognized that elevated ALP in cancer patients usually signifies that the disease has spread to the patients’ bones or livers. Malignancies of the prostate, colon, breast, lung, thyroid and other organs can metastasize to bone or liver. However, primary cancers in various organs can generate alkaline phosphatase elevations in the absence of metastasis. These tumors often produce specific forms of ALP, called isoenzymes, which increase total ALP levels on laboratory tests. One of the better-studied of these tumor isoenzymes is the Regan isoenzyme, which is expressed by a number of human cancers.
When an elevated ALP level is first detected via routine blood testing, it usually prompts a more thorough investigation to determine potential causes. Since ALP from individual organs can be differentiated to some extent, specific isoenzyme testing often narrows the search. For example, bone and liver produce distinct ALP isoenzymes, and discovery of a Regan isoenzyme elicits a search for urologic or gonadal cancers, which commonly express this isoenzyme. Interestingly, Regan isoenzymes are sometimes also found in people with ulcerative colitis or familial polyposis of the colon, both of which are known to significantly increase future cancer risk. Hence, elevated ALP in general, and the presence of a Regan isoenzyme in particular, may foretell of a tumor. For patients whose cancers have already been diagnosed, a rising ALP may signify metastasis to other organs. Conversely, cancer victims who are responding to treatment will typically see a fall in their ALP levels, which is a positive prognostic sign.
- Merck Manual of Diagnosis and Therapy, 18th Edition: Testing for Hepatic and Biliary Disorders; Mark H. Beers, M.D., Editor-in-Chief; 2006
- Clinical Chemistry; A Variant Alkaline Phosphatase in Renal Cell Carcinoma; Whitaker K, et al.; 1982
- Prostate; Immunology and Biochemistry of the Regan Isoenzyme; Fishman W; 1980