From the Guidelines
Elevated alkaline phosphatase (ALP) should be further investigated to determine its underlying cause, with a focus on distinguishing between liver and bone sources, as indicated by the most recent study 1. To approach elevated ALP, it is crucial to first assess if the elevation is isolated or accompanied by other abnormal liver enzymes. If ALP is elevated in isolation, ordering bone-specific ALP or gamma-glutamyl transferase (GGT) can help differentiate between liver and bone sources, as GGT is not found in bone but is present in the liver and other organs 1.
Common Causes and Considerations
- Liver causes: biliary obstruction, cholestasis, certain medications, and liver diseases such as primary biliary cholangitis or primary sclerosing cholangitis.
- Bone-related causes: Paget's disease, bone growth in children, healing fractures, and bone tumors.
- Other causes: pregnancy, certain cancers, or inflammatory conditions.
Management Approach
Management of elevated ALP depends on identifying and treating the underlying cause rather than the elevated enzyme level itself. This may involve:
- Additional liver function tests to assess the extent of liver involvement.
- Imaging studies like ultrasound or CT scan to evaluate the biliary tree and liver parenchyma.
- Possibly, bone scans if bone pathology is suspected.
- Patient advice to avoid alcohol and review medications with their healthcare provider to identify any potential drug-induced causes. The significance of elevated ALP lies in its role as an indicator of tissue damage or increased cellular turnover in the liver, bones, or other organs, emphasizing the need for a thorough investigation to determine the underlying cause and appropriate management strategy, as outlined in the recent study 1.
From the Research
Causes of Elevated Alkaline Phosphatase
- Elevated alkaline phosphatase (ALP) levels can be caused by various conditions, including underlying malignancy, bone disease, unsuspected parenchymal liver disease, non-malignant infiltrative liver disease, and other disorders 2.
- A study found that the most common cause of ALP elevation was due to underlying malignancy (57%), followed by bone disease (29%) 2.
- Another study noted that ALP can also originate in the intestine and placenta, and that very few cases of persistent elevations of ALP have been reported in the literature without underlying pathology 3.
Diagnosis and Evaluation
- The evaluation of abnormal liver chemistries, including ALP, should be termed liver chemistries or liver tests 4.
- Cholestatic injury is defined as disproportionate elevation of alkaline phosphatase level as compared with AST and ALT levels 4.
- For the evaluation of an alkaline phosphatase elevation determined to be of hepatic origin, testing for primary biliary cholangitis and primary sclerosing cholangitis should be undertaken 4.
- A liver biopsy may be considered when serologic testing and imaging fails to elucidate a diagnosis, to stage a condition, or when multiple diagnoses are possible 4.
Bone Alkaline Phosphatase
- Bone alkaline phosphatase (BALP) is essential for biomineralization and has been identified as a promising predictor of mortality in chronic kidney disease (CKD) 5.
- Serum BALP has been suggested as a biomarker of bone turnover in CKD-mineral and bone disorder (CKD-MBD), and may be better suited for the diagnosis and longitudinal follow-up of bone turnover than parathyroid hormone (PTH) 5.
- The linear association of BALP with mortality, compared to the U-shaped curve for PTH, is an additional advantage, making BALP more suitable than PTH as a treatment target in CKD 5.