What is the significance of elevated alkaline phosphatase (ALP) levels with normal bone isoenzyme, normal liver isoenzyme, low intestine isoenzyme, and normal placental isoenzyme?

From the Guidelines

The patient's alkaline phosphatase (ALP) test results are within normal limits, indicating no evidence of bone or liver pathology, and no further action is needed regarding these results. The total ALP level is 77, which is normal, and the distribution of isoenzymes is also normal, with the bone isoenzyme contributing 51% and the liver isoenzyme accounting for 49% of the total activity 1. The intestinal and placental isoenzymes are at 0, which is normal for the intestinal isoenzyme and expected for the placental isoenzyme in non-pregnant individuals.

The normal ALP results, in conjunction with the normal distribution of isoenzymes, suggest that there is no cholestatic liver disease or other pathology affecting the liver or bone, as elevated ALP levels can occur in cholestatic liver disease, which can show elevated ALP with or without elevated bilirubin 1. The absence of elevated intestinal isoenzyme suggests normal intestinal function, and the absence of placental isoenzyme is consistent with non-pregnancy status.

Key points to consider in this case include:

• Normal total ALP level of 77
• Normal distribution of isoenzymes, with bone isoenzyme contributing 51% and liver isoenzyme accounting for 49%
• Intestinal and placental isoenzymes at 0, which is normal
• No evidence of bone or liver pathology
• No further action needed regarding these ALP results, as they are entirely within normal limits, according to the most recent guidelines on abnormal liver function tests 1.

From the Research

Alkaline Phosphatase Isoenzymes

• The provided alkaline phosphatase isoenzyme values are:
  • Normal intestine isoenzyme: 0
  • Low placental isoenzyme: 0
  • Normal bone isoenzyme: 51
  • Normal liver isoenzyme: 49
• According to 2, the liver and bone forms of alkaline phosphatase are differently-glycosylated forms of a single gene product.
• The main value of estimating specific alkaline phosphatase isoenzymes is found in patients with co-existing bone and liver diseases, such as cancer 2.

Bone Isoenzyme

• The bone isoenzyme may be involved in mammalian bone calcification 3.
• Tissue-nonspecific alkaline phosphatase (TNAP) is strongly expressed in bone, liver, and kidney and plays a key function in the calcification of bones 4.
• The normal bone isoenzyme value of 51 suggests that bone mineralization is likely occurring normally.

Liver Isoenzyme

• The liver isoenzyme is one of the forms of alkaline phosphatase that can be elevated in hepatobiliary disease 2.
• The normal liver isoenzyme value of 49 suggests that liver function is likely normal.

Intestine and Placental Isoenzymes

• The intestinal isoenzyme is thought to play a role in the transport of phosphate into epithelial cells of the intestine 3.
• The low values of intestinal and placental isoenzymes (0) may not be indicative of any specific disease or condition, as these isoenzymes are not typically elevated in normal individuals 2, 3.

Alkaline Phosphatase Function

• Alkaline phosphatase increases inorganic phosphate local rates and facilitates mineralization as well as reduces the extracellular pyrophosphate concentration, an inhibitor of mineral formation 4.
• Alkaline phosphatase is an evolutionary conserved enzyme and widely used biomarker in clinical practice, with tissue-nonspecific alkaline phosphatase (TNALP) being one of four human isozymes 5.