From the Guidelines
Elevated alkaline phosphatase (ALP) levels can be caused by several conditions affecting the liver, bones, or other organs, with liver-related causes including bile duct obstruction, hepatitis, cirrhosis, liver cancer, and certain medications that are hepatotoxic, as noted in the most recent study 1.
Causes of Elevated ALP
The causes of elevated ALP can be broadly categorized into liver-related and bone-related causes. Liver-related causes include:
- Bile duct obstruction
- Hepatitis
- Cirrhosis
- Liver cancer
- Certain medications that are hepatotoxic Bone-related causes include:
- Paget's disease
- Bone metastases
- Fracture healing
- Osteomalacia
- Hyperparathyroidism Other causes of elevated ALP include:
- Pregnancy (placental production)
- Certain cancers
- Inflammatory bowel disease
- Sepsis
- Hyperthyroidism Some medications like phenytoin can also increase ALP levels, as mentioned in 1.
Determining the Source of Elevated ALP
When evaluating elevated ALP, it's essential to determine the source by checking for concurrent elevation of other liver enzymes (suggesting liver origin) or considering bone-specific isoenzymes if bone pathology is suspected, as recommended in 1. The pattern and degree of elevation, along with clinical symptoms, help identify the underlying cause, which is crucial for appropriate treatment.
Recent Guidelines
Recent guidelines, such as those published in 1, emphasize the importance of using magnetic resonance cholangiopancreaticography (MRCP) to diagnose sclerosing cholangitis, a condition that can cause elevated ALP levels. The guidelines also recommend excluding secondary causes of sclerosing cholangitis and considering the diagnosis in patients with elevated serum liver tests in a cholestatic pattern.
Conclusion Not Applicable
Instead, the key takeaway is that elevated ALP levels require a thorough evaluation to determine the underlying cause, and the most recent and highest-quality studies, such as 1, should be consulted to guide diagnosis and treatment.
From the Research
Causes of Increased Alkaline Phosphatase
- Paget's disease of bone (PDB) is a common cause of elevated serum alkaline phosphatase levels 2, 3, 4, 5
- Enhanced bone resorption and formation in PDB lead to an increase in alkaline phosphatase levels 4
- Vitamin D deficiency may also contribute to increased alkaline phosphatase levels in PDB patients 6
- Secondary hyperparathyroidism, which can occur in PDB patients, may also lead to elevated alkaline phosphatase levels 2
Relationship Between Alkaline Phosphatase and Paget's Disease
- Elevated serum alkaline phosphatase levels are often the only diagnostic clue for PDB 3, 4
- Alkaline phosphatase levels correlate with disease activity in PDB 4
- Bisphosphonate treatment, which is commonly used to treat PDB, can lead to a reduction in alkaline phosphatase levels 3, 5
Other Factors That May Influence Alkaline Phosphatase Levels
- Hypocalcemia and secondary hyperparathyroidism can occur in PDB patients, particularly after treatment with bisphosphonates 2
- Vitamin D status can impact alkaline phosphatase levels, with hypovitaminosis D being common in PDB patients 6
- Correction of hypovitaminosis D can lead to a reduction in alkaline phosphatase levels and improvement in symptoms 6