Raised Alkaline Phosphatase (ALP): Liver or Bone? Interpreter
Raised Alkaline Phosphatase (ALP): Liver or Bone? Interpreter
Work out where a raised alkaline phosphatase (ALP) is coming from when the rest of the liver tests are normal. Enter the ALP and your laboratory’s upper limit, then the GGT or 5′-nucleotidase and the context — pregnancy, childhood, a recent fracture, known bone disease — and the page gives the likely source (liver, bone or placenta) and the next test, following the 2018 British Society of Gastroenterology guideline.
Where is the raised ALP coming from?
ALP, GGT and context → likely source and next testA 72-year-old woman has an ALP of 210 U/L (upper limit 130) on a routine panel. ALT, bilirubin and GGT are normal. No fracture, not known to have bone disease.
The order the guideline works in
2. GGT (or 5′-nucleotidase) raised → liver: AMA and ANA, abdominal ultrasound, drug review
3. GGT normal → not liver: pregnancy (placenta), childhood (growth), fracture or bone disease
4. Otherwise bone until shown not: calcium, phosphate, PTH, vitamin D; isoenzymes if in doubt
The multiple of the upper limit = ALP ÷ upper limit — printed, but not graded: no guideline grades an isolated ALP by it
- GGT
- γ-glutamyltransferase — made in the liver and biliary tree, not in bone or placenta
- 5′-nucleotidase
- an alternative marker of hepatobiliary origin, where laboratories still offer it
- isoenzymes
- electrophoresis separating liver, bone, placental and intestinal ALP — the tie-breaker
Worked example
A 72-year-old woman has an ALP of 210 U/L (upper limit 130) on a routine panel. ALT, bilirubin and GGT are normal. No fracture, not known to have bone disease.
Multiple of the upper limit = 210 ÷ 130 = 1.62
ALT and bilirubin normal → the ALP is isolated
GGT normal → not from the liver
No pregnancy, not a child, no fracture → probably bone: check calcium, phosphate, PTH and 25-hydroxyvitamin D
Vitamin D deficiency (osteomalacia) first, then Paget's disease and metastases; isoenzymes if still unsure
Where ALP comes from
| Source | Clue | GGT | Next step |
|---|---|---|---|
| Liver and bile ducts | Itch, cholestatic drugs, inflammatory bowel disease | Raised | AMA and ANA, abdominal ultrasound, drug review |
| Bone | Vitamin D deficiency, Paget’s disease, metastases, fracture, hyperparathyroidism | Normal | Calcium, phosphate, PTH, 25-hydroxyvitamin D |
| Placenta | Pregnancy, especially later | Normal | None, unless itching (bile acids) |
| Growing bone | Childhood and adolescence | Normal (but age-specific) | Compare with a paediatric interval |
Why the GGT decides it
Alkaline phosphatase is not one enzyme but several, made in the liver and bile ducts, in bone, in the placenta and in the gut. A raised ALP with a normal ALT and bilirubin is one of the commonest questions a laboratory is asked, and the page that only converts the units (the ALP unit converter) cannot answer it. The 2018 guideline on abnormal liver blood tests from the British Society of Gastroenterology and the laboratory and liver societies answers it in one step: measure the γ-glutamyltransferase (GGT). GGT is made by the liver and bile ducts but not by bone or placenta, so a raised GGT alongside the ALP says the liver, and a normal one says look elsewhere (the GGT unit converter converts its units).
When the GGT is raised, the pattern is cholestatic. The UK primary biliary cholangitis guideline asks for antimitochondrial and antinuclear antibodies in anyone with persistently raised cholestatic tests and no other explanation, and a baseline ultrasound; the ultrasound also finds dilated ducts from stones or a stricture. Drugs cause a large share of cholestatic tests and should be reviewed. When the GGT is normal, the BSG guideline puts vitamin D deficiency first among non-hepatic causes, then Paget’s disease and bone metastases, and reminds the reader that ALP is physiologically higher in childhood, with growth, and in pregnancy, from the placenta.
The GGT is a good discriminator, not a perfect one. Alcohol and enzyme-inducing drugs raise it without cholestasis, and both a bone and a liver source can be present at once. That is when isoenzyme electrophoresis, which the guideline keeps for when “doubt still exists”, earns its place. The multiple of the upper limit is shown because readers ask for it, but no guideline grades an isolated ALP by its multiple, and this page does not pretend to. If ALT or bilirubin is abnormal as well, the question is a different one: use the R-factor calculator to classify the pattern first. This page supports, and does not replace, clinical judgement.
Frequently asked questions
What does a high ALP with a normal GGT mean?
That the ALP is probably not from the liver. Bone is the usual source — vitamin D deficiency, Paget’s disease, metastases, a healing fracture or hyperparathyroidism — and pregnancy and childhood growth raise it normally. Check calcium, phosphate, PTH and vitamin D.
What does a high ALP with a high GGT mean?
A cholestatic liver pattern. The UK guidance is to check antimitochondrial and antinuclear antibodies and to arrange an abdominal ultrasound, and to review the drug history. Alcohol and some drugs raise GGT by themselves, so if the picture does not fit, ALP isoenzymes decide.
Is a raised ALP normal in pregnancy?
Yes. The placenta makes ALP, so it rises in pregnancy, especially later on, while GGT does not. A raised GGT in pregnancy, or itching, needs bile acids and ALT to look for intrahepatic cholestasis of pregnancy.
How high is too high for ALP?
No guideline sets a multiple of the upper limit at which an isolated ALP becomes urgent; the source matters more than the size. Children and pregnant women need their own reference intervals.
Related calculators
References
- Newsome PN, Cramb R, Davison SM, et al. Guidelines on the management of abnormal liver blood tests. Gut. 2018;67(1):6–19. British Society of Gastroenterology, Association of Clinical Biochemistry and Laboratory Medicine and British Association for the Study of the Liver.
- Hirschfield GM, Dyson JK, Alexander GJM, et al. The British Society of Gastroenterology/UK-PBC primary biliary cholangitis treatment and management guidelines. Gut. 2018;67(9):1568–1594. doi:10.1136/gutjnl-2017-315259.
Not medical advice. For healthcare professionals and education. Reference intervals vary by laboratory and assay — always use your own laboratory's. Never base a dose or a treatment decision on this page alone. Full disclaimer at calcengines.com/disclaimer/