Management of Elevated Alkaline Phosphatase with Normal GGT

Understanding ALP and GGT

ALP is produced in multiple tissues including liver, bone, intestines, kidneys, and placenta, with liver and bone being the predominant sources, according to the American College of Radiology 1, 2
GGT is found in the liver, kidneys, intestine, prostate, and pancreas, but importantly, it is not found in bone, as noted by the American College of Radiology 1, 2
When ALP is elevated but GGT is normal, this strongly suggests a non-hepatic source of the ALP elevation, most commonly bone, as stated by Alimentary Pharmacology and Therapeutics 3

Normal GGT with elevated ALP indicates the elevation is likely of non-hepatic origin, and ALP isoenzyme fractionation can determine the percentage derived from liver versus bone or other tissues, according to Alimentary Pharmacology and Therapeutics 3, 4
Consider common bone conditions that elevate ALP, such as Paget's disease, osteoporosis, bone metastases, and fracture healing, as suggested by the Journal of the American College of Radiology 1 and Alimentary Pharmacology and Therapeutics 3

Avoid unnecessary hepatic imaging when GGT is normal, as this strongly indicates a non-hepatic source, according to Alimentary Pharmacology and Therapeutics 3
Don't assume liver pathology when GGT is normal, and avoid extensive hepatobiliary workup as the first step, as recommended by Alimentary Pharmacology and Therapeutics 3 and the Journal of the American College of Radiology 1, 5
Remember that some medications can affect ALP levels without indicating disease, as noted by Alimentary Pharmacology and Therapeutics 4

Bone metastases should be considered in elderly patients with elevated ALP, as this condition is a common cause of elevated ALP in this population, according to the National Comprehensive Cancer Network 6, 7
The American Cancer Society recommends bone scintigraphy as the first-line imaging for suspected bone pathology in patients with elevated ALP, as it can help identify bone metastases 6

The National Comprehensive Cancer Network recommends considering additional imaging based on initial findings and clinical suspicion, and assessing for bone pain, recent fractures, or other symptoms of bone disease 6, 7
The European Society for Medical Oncology suggests evaluating for risk factors for osteoporosis or malignancy, such as age, family history, and medication use 8

If bone metastases are suspected, comprehensive staging would be indicated if malignancy is identified, according to the National Comprehensive Cancer Network 6, 7