What are the causes of hyperphosphatasemia (elevated alkaline phosphatase (ALP) levels)?

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From the Guidelines

Elevated alkaline phosphatase (ALP) levels, also known as hyperphosphatasemia, are primarily caused by liver and bone diseases.

Causes of Hyperphosphatasemia

  • Liver diseases:
    • Cholestatic liver disease, such as primary biliary cholangitis, primary sclerosing cholangitis, and intrahepatic or extrahepatic bile duct obstruction 1
    • Viral hepatitis, chronic hepatitis, and cirrhosis 1
    • Drug-induced cholestasis and hepatic congestion due to congestive heart failure 1
  • Bone diseases:
    • Paget’s disease, bony metastases, and fracture 1
    • Rapid bone growth in children and bone disease in adults 1
  • Other causes:
    • Pregnancy, due to placental production of ALP 1
    • Infiltrative liver diseases, such as sarcoidosis, amyloidosis, and hepatic metastases 1
    • Ischemic cholangiopathy and choledocholithiasis 1 To determine the origin of elevated ALP levels, gamma-glutamyl transpeptidase (GGT) testing can be used, as GGT is found in the liver and kidneys, but not in bone 1. Fractionating alkaline phosphatase into its liver, bone, and intestinal isoenzyme fractions can also provide additional information on the etiology of ALP elevations 1.

From the Research

Causes of Hyperphosphatasemia

The causes of hyperphosphatasemia, or elevated alkaline phosphatase (ALP) levels, can be varied and include:

  • Underlying malignancy, with the most common being infiltrative intrahepatic malignancy, bony metastasis, and both hepatic and bone metastasis 2
  • Bone disease, which can account for a significant portion of cases 2, 3, 4
  • Unsuspected parenchymal liver disease, which can be a cause of elevated ALP levels, although less common 2
  • Non-malignant infiltrative liver disease, which can also contribute to elevated ALP levels 2
  • Other disorders, such as benign familial intestinal hyperphosphatasemia (BFIH) and benign transient hyperphosphatasemia, which can cause persistent elevations of ALP without underlying pathology 5, 6
  • High bone turnover, particularly in postmenopausal women, which can lead to elevated ALP levels 4
  • Certain medications, such as glucocorticoids and anticonvulsants, which can induce increased ALP activity 3
  • Physiologic changes, such as those occurring in young animals, pregnant and lactating females, and in association with high fat diets 3

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Alkaline phosphatase: beyond the liver.

Veterinary clinical pathology, 2007

Research

Persistently elevated alkaline phosphatase without hepatopathy? Literature review.

Revista espanola de enfermedades digestivas, 2024

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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