From the Guidelines
Elevated alkaline phosphatase (ALP) levels should be evaluated by determining the source of elevation through additional laboratory tests, including gamma-glutamyl transferase (GGT), 5'-nucleotidase, and isoenzyme fractionation to distinguish between hepatic and bone origins, as recommended by the most recent guidelines 1. The evaluation approach is crucial in identifying the underlying cause of elevated ALP levels, which can be due to various conditions affecting the liver or bone.
- For hepatic causes, imaging tests such as ultrasound or magnetic resonance cholangiopancreatography (MRCP) should be performed to assess for biliary obstruction, as suggested by the American College of Radiology 1.
- Bone-specific ALP and vitamin D levels can help evaluate bone-related elevations, and treatment depends entirely on the underlying cause. Some possible treatments include:
- Endoscopic retrograde cholangiopancreatography (ERCP) or surgical intervention for biliary obstruction
- Discontinuation of the offending agent for medication-induced elevations
- Ursodeoxycholic acid at 13-15 mg/kg/day for primary biliary cholangitis, as recommended by the European Association for the Study of the Liver 1
- Vitamin D supplementation (typically 1,000-2,000 IU daily) for deficiency, bisphosphonates for Paget's disease (such as zoledronic acid 5 mg IV once yearly), or addressing hyperparathyroidism for bone-related elevations Regular monitoring of ALP levels every 3-6 months is recommended during treatment to assess response, as the approach is guided by understanding that ALP is produced primarily in liver and bone tissue, and elevations reflect underlying pathology in these systems that must be specifically identified for effective management 1.
From the FDA Drug Label
The FDA drug label does not answer the question.
From the Research
Evaluation Approach for Elevated Alkaline Phosphatase (ALP) Levels
- The evaluation of elevated ALP levels should consider various causes, including underlying malignancy, bone disease, unsuspected parenchymal liver disease, non-malignant infiltrative liver disease, and other disorders 2.
- A retrospective cohort study found that the most common cause of ALP elevation was due to underlying malignancy (57%), followed by bone disease (29%) 2.
- The pathophysiology of ALP should be understood, including its function in the liver and how it is eliminated from the serum 3.
- Defective enzyme elimination could play a major role in the pathogenesis of serum ALP elevations 3.
Treatment Approach for Elevated Alkaline Phosphatase (ALP) Levels
- The treatment approach for elevated ALP levels depends on the underlying cause, and providers should be aware of the potential clinical significance of an elevated ALP 2.
- In cases of primary biliary cholangitis (PBC) with normal ALP levels, timely initiation of treatment with ursodeoxycholic acid is crucial to prevent progression to cirrhosis and liver failure 4.
- An algorithm can be utilized as a guide in a primary care setting to arrive at the diagnosis of transient hyperphosphatasemia (THP) and avoid further tests or referrals in children with elevated ALP levels 5.
- It is essential to determine the isoenzymes of ALP in some cases, such as in the context of benign familial intestinal hyperphosphatasemia (BFIH) without underlying pathology 6.
Important Considerations
- Elevated ALP levels can be found in multiple hepatobiliary diseases and in bone diseases, and ALP can also originate in the intestine and placenta 6.
- A high proportion of patients with normal ALP levels and positive anti-mitochondrial (AMA) and/or PBC-specific anti-nuclear autoantibodies (ANA) may have primary biliary cholangitis (PBC) 4.
- Current guidelines for the diagnosis of PBC may not cover the whole extent of PBC presentation, with important clinical implications in terms of timely treatment initiation 4.