From the Guidelines
Elevated alkaline phosphatase (ALP) levels should be rechecked with a repeat blood test in 2-4 weeks to confirm the finding, along with additional liver function tests including AST, ALT, GGT, bilirubin, and albumin. If the elevation persists, further investigation is warranted with a hepatic isoenzyme test to determine if the source is liver or bone, as suggested by 1. Imaging studies such as an abdominal ultrasound or CT scan may be necessary to evaluate the liver, gallbladder, and bile ducts, especially if cholestatic liver disease is suspected, which can be indicated by elevated ALP with or without elevated bilirubin 1. Bone-specific tests like vitamin D levels, calcium, phosphorus, and parathyroid hormone should be considered if bone disease is suspected, as ALP is also produced in bone and can be elevated in conditions such as Paget’s disease or bony metastases 1. Medication review is important as certain drugs like antibiotics, anti-seizure medications, and statins can cause ALP elevation, and monitoring should be done before and after treatment, as recommended by 1. The timing of follow-up depends on the degree of elevation - mild elevations (less than 2-3 times normal) may be monitored over 1-3 months, while significant elevations require more urgent evaluation, considering the potential for liver or bone disease. Some key points to consider in the diagnostic workup include:
- Concomitantly elevated GGT can help confirm that an elevated ALP originates from the liver and indicates cholestasis 1
- Fractionating alkaline phosphatase into its liver, bone, and intestinal isoenzyme fractions can also be very informative 1
- Glutamate dehydrogenase (GLDH) is a mitochondrial enzyme which can provide further supporting evidence that aminotransferase elevations are of hepatic origin 1
- The severity of abnormal aminotransferase can be classified as mild, moderate, or severe, and this classification can guide the urgency of the diagnostic workup 1
From the Research
Causes of Elevated Alkaline Phosphatase
- The most common cause of elevated alkaline phosphatase (ALP) is underlying malignancy, accounting for 57% of cases, with infiltrative intrahepatic malignancy, bony metastasis, and both hepatic and bone metastasis being common causes 2
- Bone disease is another significant cause of elevated ALP, accounting for 29% of cases 2
- Unsuspected parenchymal liver disease, non-malignant infiltrative liver disease, and other disorders also contribute to elevated ALP levels 2
Diagnostic Approach
- An algorithm can be used to determine when a "wait and see" approach is optimal for children with elevated ALP levels, avoiding unnecessary tests or referrals 3
- Measuring the bone-specific isoform of ALP (B-ALP) rather than total ALP can provide more accurate information on bone turnover and disease 4
Pathophysiology and Clinical Significance
- Elevated ALP can be caused by defective elimination of the enzyme, which is a seldom-discussed but important aspect of its pathophysiology 5
- ALP plays a crucial role in bone mineralization and is involved in the pathogenesis of ectopic calcification, inflammation, and cardiovascular disease 6
- The association between ALP, vitamin K, bone metabolism, and fracture risk in patients with chronic kidney disease (CKD) highlights the importance of ALP as a biomarker and potential treatment target 6