GGT Does Not Increase with Bone Destruction
GGT is found in the liver, kidneys, intestine, prostate, and pancreas, but not in bone, making it a reliable marker to distinguish hepatobiliary disease from bone pathology. 1
Why GGT Helps Differentiate Bone from Liver Disease
When alkaline phosphatase (ALP) is elevated, GGT serves as the key discriminator between hepatic and non-hepatic sources:
- Elevated GGT confirms hepatobiliary origin of elevated ALP and indicates cholestasis 1
- Normal GGT with elevated ALP suggests bone origin (e.g., Paget's disease, bone metastases, fractures) 1, 2
- This distinction is critical because ALP is present in both liver and bone tissue, while GGT is absent from bone 1
Clinical Evidence Supporting GGT's Specificity
A rigorous study in Duchenne muscular dystrophy patients—who have massive skeletal muscle damage with creatine kinase levels 14 to 200 times normal—demonstrated that not a single patient showed GGT outside the normal control range, validating that GGT does not rise with muscle or skeletal tissue destruction 3. This finding is essential for distinguishing hepatotoxicity from musculoskeletal damage.
Practical Diagnostic Algorithm
When encountering elevated ALP:
- Measure GGT concurrently to determine the source 1, 4
- If GGT is elevated (>2× ULN): Pursue hepatobiliary workup with abdominal ultrasound, then MRCP if needed 5, 4
- If GGT is normal: Consider bone-specific causes and obtain bone-specific ALP or bone scan if clinically indicated 2
- If GGT is equivocal: Obtain ALP isoenzyme fractionation to determine percentage from liver versus bone 4
Important Caveats
- In advanced liver disease with extensive fibrosis, GGT elevates regardless of etiology, but this represents hepatic pathology, not bone destruction 1
- Bone-specific ALP measurement becomes less useful in chronic liver disease because it is difficult to measure accurately when liver ALP is already elevated 2
- Treatments like bisphosphonates and denosumab can alter ALP levels despite underlying bone pathology, but these changes reflect bone turnover, not GGT elevation 2