What is the differential diagnosis for elevated alkaline phosphatase (Alk Phos) levels, specifically distinguishing between liver and bone origins?

From the Guidelines

Elevated alkaline phosphatase (ALP) levels can be distinguished between liver and bone origins by assessing gamma-glutamyl transferase (GGT) levels, as concomitantly elevated GGT suggests a liver origin, while normal GGT with high ALP points toward bone pathology 1. To differentiate between liver and bone sources of elevated ALP, clinicians should consider the following:

• Liver-derived ALP elevations typically occur alongside other abnormal liver function tests like elevated bilirubin, AST, or ALT, and are associated with conditions such as biliary obstruction, cholestasis, hepatitis, or infiltrative liver diseases 1.
• Bone-derived ALP elevations often occur in isolation without other liver abnormalities and are seen in conditions like Paget's disease, osteomalacia, healing fractures, bone metastases, or hyperparathyroidism 1.
• The clinical context provides important clues - bone pain, recent fractures, or known bone disorders suggest bone origin, while jaundice, right upper quadrant pain, or known liver disease suggests hepatic origin 1.
• Age can also be relevant, as growing children naturally have higher bone-derived ALP levels due to bone development 1.
• Isoenzyme testing of ALP can also identify the specific tissue source, and fractionating alkaline phosphatase into its liver, bone, and intestinal isoenzyme fractions can be informative 2.
• Additionally, measurements of 5′nucleotidase levels and DBIL can provide further information on the etiology of ALP elevations 2. It is essential to consider these factors to accurately diagnose the origin of elevated ALP levels and provide appropriate treatment, as delayed or incorrect diagnosis can lead to increased morbidity, mortality, and decreased quality of life. Therefore, a comprehensive diagnostic approach, including laboratory tests and clinical evaluation, is crucial in distinguishing between liver and bone origins of elevated ALP levels 1, 2.

From the Research

Differential Diagnosis for Elevated Alkaline Phosphatase (Alk Phos) Levels

The differential diagnosis for elevated alkaline phosphatase (Alk Phos) levels involves distinguishing between liver and bone origins. Key points to consider include:

• Elevated activity in the circulation is universally recognized as a marker for skeletal or hepatobiliary disease 3
• The main source of elevated serum alkaline phosphatase activity in the serum of patients with hepatobiliary diseases is the liver isoenzyme 4
• A normal gamma-glutamyl transpeptidase suggests bone origin, while an elevated gamma-glutamyl transpeptidase suggests liver origin 5
• Elevated ALP in postmenopausal women is mainly caused by high bone turnover 6

Laboratory Tests for Differential Diagnosis

Laboratory tests that can aid in the differential diagnosis of elevated Alk Phos levels include:

• Gamma-glutamyl transpeptidase (GGT) to differentiate between bone and liver origin 5
• Serum alkaline phosphatase isozyme pattern by electrophoresis to differentiate various pathological states 5
• Bone-specific alkaline phosphatase (BAP) to assess bone turnover 6
• Markers of liver function, such as total bilirubin and other liver enzymes, to assess liver disease 7, 4

Clinical Considerations

Clinical considerations that can aid in the differential diagnosis of elevated Alk Phos levels include:

• Patient demographics, such as age and sex 6
• Medical history, such as presence of liver or bone disease 3, 7
• Physical examination findings, such as presence of jaundice or bone pain 7
• Other laboratory test results, such as complete blood count and electrolyte panel 7