What is the workup for elevated alkaline phosphatase (ALP)?

From the Guidelines

Elevated alkaline phosphatase should be investigated with a thorough history and physical examination, followed by targeted laboratory testing, including liver function tests, complete blood count, and fractionation of alkaline phosphatase isoenzymes to determine the source, as recommended by the most recent guidelines 1. The initial workup should include liver function tests (AST, ALT, bilirubin, GGT) to assess for liver pathology, and fractionation of alkaline phosphatase isoenzymes to distinguish between hepatic, bone, intestinal, or placental origins. Some key points to consider in the workup include:

• Measuring GGT to confirm whether elevated ALP is of hepatobiliary origin 1
• Assessing for biliary obstruction, masses, or parenchymal disease with ultrasound of the liver and biliary system if liver pathology is suspected
• Evaluating for bone involvement with calcium, phosphorus, vitamin D levels, and parathyroid hormone, potentially followed by bone scans or skeletal surveys
• Considering more specialized imaging such as MRCP, ERCP, or liver biopsy if the source remains unclear after initial testing The elevated alkaline phosphatase requires investigation because it can indicate various conditions, including cholestasis, bone disorders (Paget's disease, osteomalacia), certain cancers, or medication effects, as noted in recent studies 1. Treatment depends entirely on identifying and addressing the underlying cause rather than treating the enzyme elevation itself, and should be guided by the most recent and highest quality evidence, such as the recommendations for detection, assessment, and management of suspected drug-induced liver injury during clinical trials in oncology patients 1.

From the Research

Elevated Alkaline Phosphatase

Elevated alkaline phosphatase (ALP) levels can indicate various conditions, including liver and bone diseases. The following are potential causes and workup for elevated ALP:

• Liver diseases:
  • Cholestasis: Elevated ALP and gamma-glutamyl transferase (G-GT) levels can indicate cholestasis, a condition where bile flow is blocked 2.
  • Alcoholic liver disease: Elevated ALP and G-GT levels can also be seen in alcoholic liver disease 2.
• Bone diseases:
  • Bone growth or repair: ALP is involved in bone mineralization, and elevated levels can indicate bone growth or repair 3.
• Other conditions:
  • Defective enzyme elimination: A novel concept suggests that defective elimination of ALP from the serum can contribute to elevated levels 3.
  • Cardiovascular disease: Elevated ALP levels have been associated with an increased risk of cardiovascular disease mortality 4.

Workup for Elevated Alkaline Phosphatase

The workup for elevated ALP levels includes:

• Liver function tests: To evaluate liver damage or disease, including aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels 2, 5.
• Imaging studies: To evaluate liver or bone pathology, such as ultrasound or MRI 5.
• Medical history: To assess for potential causes of elevated ALP, such as alcohol use or medication-induced liver injury 2, 5.
• Further testing: To evaluate for specific conditions, such as viral hepatitis or autoimmune hepatitis 5.