Interpreting alkaline phosphatase in clinical practice: integrating analytical advances and physiological context

Abstract

Accurate interpretation of serum alkaline phosphatase (ALP) levels is crucial in clinical practice, requiring a nuanced understanding of both analytical methods and physiological determinants. Recent advancements in ALP assay techniques, particularly the adoption of the IFCC reference method, have led to higher measured ALP values and necessitated a reassessment of reference intervals. This review integrates analytical developments with physiological context to guide clinicians in interpreting ALP results. Levels of ALP are influenced by age, gender, physiological states such as pregnancy and menopause, and anthropometric factors including body mass index and bone density. The International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) method, now widely implemented, yields results that are approximately 10% higher than those from previous assays, impacting reference interval accuracy and clinical flagging rates. Clinical causes of elevated ALP span hepatobiliary and bone disorders, malignancies, endocrine conditions and benign transient hyperphosphatasemia, while reduced ALP may signal rare genetic, hepatic or nutritional disorders. The use of gamma-glutamyl transferase as a diagnostic adjunct enhances specificity for hepatic sources of ALP elevation. Artefacts such as sample handling and reagent variability remain challenges in assay consistency. This article underscores the importance of correlating ALP results with clinical context, other laboratory findings and updated reference intervals. Ongoing education and harmonisation of reference intervals are essential for effective clinical decision-making and minimising unnecessary investigations, ensuring ALP remains a valuable tool in patient assessment.