From the Guidelines
Elevation of alkaline phosphatase (ALP) should be evaluated with a thorough history and physical examination, followed by targeted laboratory testing, including gamma-glutamyl transferase (GGT) to distinguish between liver and bone sources, as recommended by the American College of Radiology in 2023 1. When evaluating elevated ALP, it is essential to determine if the elevation is isolated or accompanied by other liver enzyme abnormalities.
- Order GGT to distinguish between liver and bone sources—if GGT is also elevated, a hepatobiliary source is likely, as GGT is not found in bone and is a more specific indicator of liver disease 1.
- For suspected liver disease, obtain a complete hepatic panel including AST, ALT, bilirubin, and albumin to assess the extent of liver damage and guide further evaluation.
- Imaging studies such as ultrasound or CT scan of the liver and biliary tract are essential to evaluate for obstruction, masses, or inflammation, as choledocholithiasis is the most common cause of extrahepatic biliary obstruction and elevated ALP of liver origin 1. If bone disease is suspected (normal GGT with elevated ALP), consider bone-specific ALP isoenzyme testing, vitamin D levels, and bone imaging to evaluate for conditions such as Paget's disease or bony metastases. Additional testing may include ALP isoenzyme fractionation to determine the tissue source, and evaluation for specific conditions like primary biliary cholangitis or Paget's disease depending on clinical presentation, as the patient's age, symptoms, medication history, and comorbidities can guide the evaluation pathway 1.
From the Research
Elevated Alkaline Phosphatase (ALP) Levels
Elevated ALP levels can be an indicator of various health issues, including bone or liver disease.
- Bone-specific alkaline phosphatase (B-ALP) is an isoform of ALP found in bone tissue and can predict fractures and heterotopic ossification 2.
- ALP plays a critical function in the formation of hard tissue, and its increased levels can facilitate mineralization 3.
Association with Cardiovascular Disease
Elevated ALP levels have been associated with an increased risk of cardiovascular disease (CVD), coronary heart disease (CHD), and stroke.
- A prospective cohort study found that higher ALP levels, even within the normal range, were significantly associated with increased risks of CVD, in a dose-dependent manner 4.
- The study suggested that regular monitoring of ALP levels may help in improving the early identification of the population at higher CVD risk 4.
Role in Bone Mineralization
ALP is essential for biomineralization, and bone alkaline phosphatase (BALP) has been identified as a promising predictor of mortality in chronic kidney disease (CKD) 5.
- BALP has been suggested as a biomarker of bone turnover in CKD-mineral and bone disorder (CKD-MBD), with a lower variability compared to parathyroid hormone (PTH) 5.
- The linear association with mortality, compared to the U-shaped curve for PTH, makes BALP a more suitable treatment target in CKD 5.
Clinical Implications
The measurement of ALP levels, particularly B-ALP, can provide valuable information for the diagnosis and management of various health conditions.