From the Guidelines
Elevated alkaline phosphatase (ALP) is a nonspecific indicator of potential liver, bone, or biliary tract problems, and its significance depends on the level of elevation and the presence of other symptoms or abnormal test results. According to the most recent study 1, ALP is produced mainly in the liver and is present in the canalicular membrane of the hepatocyte, but it can also be found in bone and in smaller amounts in the intestines, kidneys, and white blood cells. The study suggests that measurements of gamma-glutamyl transferase (GGT) can indicate whether pathologically elevated ALP is of hepatic or nonhepatic origin.
Some common causes of elevated ALP include:
- Liver conditions like hepatitis, cirrhosis, or bile duct obstruction
- Bone disorders such as Paget's disease, bone tumors, or healing fractures
- Pregnancy
- Certain medications
- Some intestinal conditions
Further investigation typically includes additional blood tests like GGT to determine if the elevation comes from liver or bone sources, imaging studies, and possibly biopsies. Treatment targets the underlying cause rather than the ALP level itself, and if you have elevated ALP, your doctor will likely recommend additional testing to identify the specific cause before determining appropriate treatment 1. It's also important to note that the degree of ALP elevation can vary, and in some cases, such as primary biliary cholangitis (PBC), ALP levels can range from 2 to approximately 10 x ULN 1.
In terms of clinical trials, reduction in ALP has been used as a primary efficacy endpoint, and an ALP of at least >1.5× ULN is normally required for clinical trial inclusion 1. However, it's essential to consider the underlying cause of the elevated ALP and to use additional tests like GGT to determine the origin of the elevation. The upper limit for ALP exclusion has typically not been specified in PBC clinical trials, but it seems prudent to exclude patients with ALP >10× ULN from trial participation, especially in early phase trials 1.
From the FDA Drug Label
Alendronate decreases bone resorption without directly inhibiting bone formation In clinical studies of up to two years' duration, alendronate sodium 5 and 10 mg/day reduced cross-linked N-telopeptides of type I collagen (a marker of bone resorption) by approximately 60% and reduced bone-specific alkaline phosphatase and total serum alkaline phosphatase (markers of bone formation) by approximately 15 to 30% and 8 to 18%, respectively Serum alkaline phosphatase, the most frequently used biochemical index of disease activity, provides an objective measure of disease severity and response to therapy.
Elevated ALP (Alkaline Phosphatase) levels may indicate increased bone turnover or disease activity, such as in Paget's disease of bone.
- In the context of alendronate treatment, a decrease in ALP levels is expected as the drug reduces bone resorption and formation.
- However, if ALP levels are elevated, it may suggest that the treatment is not effectively reducing bone turnover or that there is an underlying condition that is causing increased bone activity.
- Clinical correlation is necessary to determine the cause of elevated ALP levels and to adjust treatment accordingly 2.
From the Research
Elevated ALP Levels
Elevated serum alkaline phosphatase (ALP) levels can be an indicator of various bone-related conditions.
- In the context of Paget's disease of bone (PDB), an elevated ALP level correlates with disease activity 3.
- Serum total ALP is recommended as a first-line biochemical screening test in combination with liver function tests to screen for the presence of metabolically active PDB 4.
- ALP levels can also be affected by treatment, as bisphosphonates, which are commonly used to treat PDB, can lead to hypocalcemia and secondary hyperparathyroidism, potentially impacting ALP levels 5.
Diagnostic Considerations
- Characteristic radiographic findings and nuclear scintigraphy of the bone are used to confirm the diagnosis of PDB 3.
- Elevated ALP levels, in combination with other diagnostic tests, can help identify patients with PDB 4, 3.
- It is essential to consider other potential causes of elevated ALP levels, such as liver disease, before attributing them to PDB 4.