Diagnostic Approach to Abnormal Alkaline Phosphatase Value

Alkaline phosphatase (ALP) is abundantly represented in nature, being fundamental for a number of processes. In addition to its fundamental function in skeletal mineralization, its roles in the pathogenesis of other diseases are being explored. The measurement of total ALP activity in serum or in plasma is a useful biomarker in clinical practice. Indeed, routine measurement of serum total ALP is a long-standing established part of initial biochemical evaluation of patients both in the hospital setting and on an ambulatory basis. Raised or reduced values of this enzyme activity are indicative of a number of diseases, most commonly affecting the skeleton and the biliary tract. Electrophoretic assays are preferable for visualizing and investigating the cause of increased serum total ALP activities, and bone ALP immunoassays are preferable for investigating and monitoring individuals with bone and mineral metabolic abnormalities. Here, we give a holistic vision of this fundamental enzyme, suggesting a clinical approach to the identification of diseases causing abnormal values. Finally, a therapeutic role has emerged as substitutive therapy in patients with hypophosphatasia, even though ongoing and future studies are exploring its role in other therapeutic areas. This narrative review was based on articles found by searching PubMed from its inception until July 2024 for the terms alkaline phosphatases, isozymes, isoforms, bone alkaline phosphatase, liver alkaline phosphatase, intestinal alkaline phosphatase, placental alkaline phosphatase, liver function tests, γ-glutamyltransferase, skeletal diseases, and liver diseases. We limited our research to papers published in the English language, with emphasis placed on those describing differential diagnosis whenever available.