How to work up a 70-year-old patient with significantly elevated alkaline phosphatase (ALP) level?

From the Guidelines

When working up a 70-year-old patient with significantly elevated alkaline phosphatase (ALP) of 750, begin with a thorough history and physical examination focusing on symptoms of liver, bone, or biliary disease, and order fractionation of ALP to determine the source of elevation, as recommended by the American College of Radiology in their 2023 guidelines 1.

The initial step in evaluating elevated ALP involves differentiating between liver/biliary and bone origins, as ALP is produced in both tissues.

• Key considerations include:
  • Ordering comprehensive liver function tests (AST, ALT, bilirubin, albumin) to assess for liver damage or disease
  • Conducting a complete blood count to evaluate for signs of infection, inflammation, or malignancy
  • Performing abdominal ultrasound to evaluate for biliary obstruction or liver pathology
  • Reviewing the patient's medication list, as certain drugs can elevate ALP levels, such as phenytoin

If the elevation is suspected to be of liver/biliary origin, as indicated by concomitantly elevated GGT, further biliary evaluation with MRCP or ERCP may be necessary, as outlined in the 2023 American College of Radiology guidelines 1.

• Additional considerations for liver/biliary origin include:
  • Evaluating for choledocholithiasis, the most common cause of extrahepatic biliary obstruction
  • Assessing for malignant obstruction, biliary strictures, and infections
  • Considering infiltrative liver diseases such as sarcoidosis, amyloidosis, and hepatic metastases

For bone-origin ALP elevation,

• Key tests include:
  • Calcium, phosphate, PTH, and vitamin D levels to evaluate for bone metabolism disorders
  • Bone imaging such as skeletal survey or bone scan to assess for Paget's disease, bony metastases, or fractures

In asymptomatic patients with isolated ALP elevation, monitoring levels over 3-6 months before extensive workup may be appropriate, as some elevations may be transient or benign.

• However, given the patient's age and significantly elevated ALP level, a thorough and timely evaluation is crucial to rule out underlying conditions that may impact morbidity, mortality, and quality of life.

From the Research

Workup of Elevated Alkaline Phosphatase

To work up a 70-year-old patient with a significantly elevated alkaline phosphatase (ALP) level of 750, the following steps can be considered:

• Determine the source of the elevated ALP: This can be done by measuring bone-specific ALP or fractionating the ALP to determine if it is of bone or liver origin 2, 3.
• Check for symptoms: Common clinical manifestations of Paget's disease, a possible cause of elevated ALP, include bone pain, bowing of long bones, enlarged skull, and hearing loss 4.
• Perform imaging studies: Characteristic radiographic findings can confirm the diagnosis of Paget's disease, and nuclear scintigraphy of the bone is the most sensitive test 4.
• Rule out other causes: Other possible causes of elevated ALP include sepsis, malignant obstruction, AIDS, and benign intrahepatic disease 5.
• Check for liver disease: Liver disease can also cause elevated ALP levels, and measurements of bone-specific ALP can help distinguish between bone and liver disease 2.

Possible Causes of Elevated ALP

Some possible causes of elevated ALP levels include:

• Paget's disease of bone: A common bone disorder characterized by disorganized bone remodeling 4.
• Sepsis: Can cause extremely high elevations of ALP, even with normal bilirubin levels 5.
• Malignant obstruction: Can cause elevated ALP levels, especially in patients with biliary obstruction 5.
• AIDS: Can cause elevated ALP levels, especially in patients with sepsis or other infections 5.
• Bone metastases: Can cause elevated ALP levels, and serum ALP may be a useful marker in prognostic algorithms for patients with extremity metastatic disease 6.

Diagnostic Tests

Some diagnostic tests that may be useful in evaluating elevated ALP levels include:

• Bone-specific ALP: Can help distinguish between bone and liver disease 2, 3.
• Total ALP: Can be used to assess disease activity and response to treatment in Paget's disease 3.
• Osteocalcin: Can be used as a formation marker to assess bone turnover 3.
• Procollagen type 1 N-terminal propeptide (P1NP): Can be used as a formation marker to assess bone turnover 3.
• Telopeptides: Can be used to assess bone resorption 3.