From the Guidelines
Elevated alkaline phosphatase (ALP) levels can originate from either liver or bone sources, and determining the source is crucial for proper treatment and management, as it directly impacts morbidity, mortality, and quality of life. When ALP is elevated, it is essential to determine the source to provide appropriate care. For liver-sourced elevations, additional liver function tests like GGT, ALT, AST, and bilirubin should be checked, as these are often elevated together in liver disease 1. For bone-sourced elevations, calcium, phosphate, vitamin D levels, and bone-specific ALP isoenzymes should be measured. Liver causes include hepatitis, biliary obstruction, medications, and cirrhosis, while bone causes include Paget's disease, osteomalacia, hyperparathyroidism, bone metastases, and healing fractures.
Diagnostic Approach
To differentiate between liver and bone sources of elevated ALP, measurements of GGT can be helpful, as GGT is found in the liver and other tissues but not in bone 1. Concomitantly elevated GGT can indicate that an elevated ALP originates from the liver, suggesting cholestasis. If the liver is suspected to be the source of elevated ALP, imaging of the biliary tree may be necessary to determine the etiology of extrahepatic or intrahepatic cholestasis.
Treatment and Management
Treatment depends on the underlying cause - for liver issues, addressing the primary liver disease is key, while bone-related elevations require treating the specific bone condition 1. Imaging studies like ultrasound for liver or bone scans may be necessary for diagnosis. ALP elevations occur because this enzyme is produced by both liver and bone tissues, with different isoenzymes that can be distinguished through specialized testing if the source remains unclear after initial evaluation. The most recent and highest quality study 1 emphasizes the importance of determining the source of ALP elevation to guide appropriate management and improve patient outcomes.
Key Considerations
- Elevated ALP levels are nonspecific and can occur in various conditions affecting the liver or bone.
- GGT measurements can help differentiate between liver and non-liver sources of elevated ALP.
- Treatment should be tailored to the underlying cause of ALP elevation, whether it be liver disease, bone disease, or another condition.
- Recent guidelines 1 highlight the need for a comprehensive diagnostic approach to elevated ALP levels, including the use of additional liver function tests and imaging studies as necessary.
From the Research
Implications of Elevated Alkaline Phosphatase (ALP) Levels
Elevated ALP levels in both the liver and bones can have several implications, including:
- Bone disease with increased osteoblastic activity 2
- Hepatobiliary disease with partial or complete biliary obstruction 2
- Transient hyperphosphatasemia in children 2
- Underlying malignancy, such as infiltrative intrahepatic malignancy, bony metastasis, or both hepatic and bone metastasis 3
- Unsuspected parenchymal liver disease 3
- Non-malignant infiltrative liver disease 3
- Other disorders, such as benign familial hyperphosphatasemia 4
Diagnostic Considerations
To differentiate between bone and liver origins of elevated ALP, the following tests can be useful:
- Gamma-glutamyl transpeptidase, which is often elevated in liver disease 2
- Serum alkaline phosphatase isozyme pattern by electrophoresis, which can help differentiate various pathological states 2
- Specific estimation of liver and bone forms of alkaline phosphatase, which can be valuable in patients with co-existing bone and liver diseases 5
Clinical Significance
Elevated ALP levels can have significant clinical implications, including:
- Association with metastatic intrahepatic malignancy and other important disorders 3
- High mortality rate, with 47% of patients dying within an average of 58 months after identification of isolated, elevated ALP 3
- Need for early recognition and diagnosis to avoid unnecessary diagnostic tests and improve patient outcomes 4, 3