From the Guidelines
Alkaline phosphatase isoenzyme testing is crucial for determining the source of elevated ALP levels, particularly when total ALP is elevated, to differentiate between liver, bone, intestinal, or placental origins of the enzyme. This is because ALP is produced mainly in the liver and is present in the canalicular membrane of the hepatocyte, but it is also found in bone and in smaller amounts in the intestines, kidneys, and white blood cells 1. When interpreting ALP levels, it is essential to consider the clinical context, as elevation of ALP is nonspecific and can occur in various conditions affecting the liver, including cirrhosis, chronic hepatitis, viral hepatitis, congestive heart failure, and ischemic cholangiopathy.
Some key points to consider when evaluating ALP levels include:
- Measurements of GGT can indicate whether pathologically elevated ALP is of hepatic or nonhepatic origin, as GGT is found in the liver and in the kidneys, intestine, prostate, and pancreas, but not in the bone 1.
- Concomitantly elevated GGT can help confirm that an elevated ALP originates from the liver and indicates cholestasis.
- If the liver is suspected to be the source of elevated ALP, together with a review of the patient’s clinical history and medications, imaging of the biliary tree may be necessary to determine the etiology of extrahepatic or intrahepatic cholestasis 1.
- Isolated elevated ALP of hepatic origin that persists over time suggests a chronic cholestatic process, such as partial bile duct obstruction, primary biliary cholangitis, primary sclerosing cholangitis, or drug-induced cholestasis.
In terms of testing, isoenzyme testing can differentiate between liver, bone, intestinal, or placental origins of the enzyme, and the test involves electrophoresis or heat fractionation to separate the different isoenzymes based on their unique properties 1. The test requires a simple blood draw, with no special preparation needed, though fasting for 10-12 hours may be recommended. Results are typically available within 1-3 days. This test is particularly useful when standard liver function tests show isolated ALP elevation without clear cause, helping clinicians determine appropriate follow-up testing and treatment based on the identified source of the elevated enzyme.
From the Research
Alkaline Phosphatase Isoenzyme Lab
- The measurement of bone proteins and peptides, including alkaline phosphatase (AP), has been useful in the diagnosis and management of patients with skeletal disease 2.
- Alkaline phosphatase isoenzymes can be specific to certain tissues, such as bone or liver, and can be used to assess different aspects of bone cell function 2, 3.
- In patients with Paget's disease, bone alkaline phosphatase (BAP) is increased in the serum and correlates better with total AP than with bone Gla protein (BGP) 2.
- The intestinal isoenzyme of alkaline phosphatase can be elevated in patients with chronic renal failure, and the kidney is the likely source of this increase 3.
- Defective elimination of alkaline phosphatase can play a major role in the pathogenesis of serum alkaline phosphatase elevations 4.
Clinical Applications
- Alkaline phosphatase levels can be used to evaluate the activity of Paget's disease in clinical practice, but may underestimate the activity of Pagetic bone in localized forms of the disease 5.
- Biochemical measurements of bone turnover, including alkaline phosphatase, can provide an objective assessment of disease activity and response to treatment in Paget's disease 6.
- Different markers of bone turnover, such as osteocalcin and procollagen type 1 N-terminal propeptide, can be used to assess bone formation and resorption 6.
- The choice of marker may depend on factors such as availability, interassay variation, and cost, with total alkaline phosphatase being a commonly used test for routine use 6.