From the Guidelines
An alkaline phosphatase (ALP) level of 621 is significantly elevated and requires prompt medical evaluation to determine the underlying cause, with the most common sources being liver disorders or bone conditions. This elevation is above the normal range, which is typically between 40-130 IU/L for adults 1. The underlying cause of the elevated ALP can be determined through additional testing, including gamma-glutamyl transferase (GGT) to differentiate between liver and bone sources, as well as other liver function tests, imaging studies of the liver and biliary system, and possibly bone-specific ALP isoenzymes.
Possible Causes
- Liver disorders such as bile duct obstruction, hepatitis, or cirrhosis
- Bone conditions like Paget's disease, bone metastases, or healing fractures
- Cholestatic liver disease, such as primary biliary cholangitis, primary sclerosing cholangitis, intrahepatic or extrahepatic bile duct obstruction, and drug-induced cholestasis 1
Recommended Testing
- Gamma-glutamyl transferase (GGT) to differentiate between liver and bone sources
- Other liver function tests
- Imaging studies of the liver and biliary system, such as magnetic resonance cholangiopancreaticography (MRCP) 1
- Possibly bone-specific ALP isoenzymes
Treatment
Treatment will depend entirely on the underlying cause rather than treating the elevated ALP itself. For example, if biliary obstruction is present, procedures to relieve the blockage may be needed, while bone disorders might require specific medications. This elevation should not be ignored as it may indicate serious underlying pathology, and patients should avoid alcohol and medications that could further stress the liver until a diagnosis is established 1.
From the Research
Alkaline Phosphatase
- Alkaline phosphatase (ALP) is a commonly obtained laboratory test, but its diagnostic specificity is limited because it is found in multiple tissues 2
- The measurement of total ALP activity in serum or in plasma is a useful biomarker in clinical practice, with raised or reduced values indicative of various diseases, most commonly affecting the skeleton and the biliary tract 3
- ALP is abundantly represented in nature and is fundamental for several processes, including skeletal mineralization, and its roles in the pathogenesis of other diseases are being explored 3
Causes of Elevated ALP
- The most common cause of ALP elevation is due to underlying malignancy, with 57% of patients having an isolated, elevated ALP of unknown etiology 2
- Bone disease, unsuspected parenchymal liver disease, non-malignant infiltrative liver disease, and other disorders also account for elevated ALP levels 2
- Defective enzyme elimination could play a major role in the pathogenesis of serum alkaline phosphatase elevations 4
Clinical Significance
- An isolated, elevated ALP of unclear etiology is associated with several specific and important disorders, including metastatic intrahepatic malignancy 2
- Providers should be aware of the potential clinical significance of an elevated ALP, and electrophoretic assays are preferable for visualizing and investigating the cause of increased serum total ALP activities 3
- Bone-specific alkaline phosphatase (B-ALP) is an isoform of ALP found in bone tissue and can predict fractures and heterotopic ossification 5
Treatment and Management
- Alkaline phosphatase is a potential treatment target for cardiovascular and mineral bone disorders in chronic kidney disease 6
- Recent advances in pharmacological strategies have the potential to modulate the expression of ALP directly and indirectly in CKD-mineral and bone disorder (CKD-MBD) 6
- A target value below 120 U/L is associated with improved survival, and further experimental and clinical research should explore interventional strategies with optimal risk-benefit profiles 6