From the Guidelines
High alkaline phosphatase (ALP) levels in the blood indicate increased enzyme activity that may suggest underlying health issues, and the most recent evidence suggests that a comprehensive diagnostic approach is necessary to determine the cause. When ALP is elevated, further investigation is needed to determine the cause, which commonly includes liver disorders (hepatitis, cirrhosis, bile duct obstruction), bone conditions (Paget's disease, fractures, bone tumors), or other causes like pregnancy, certain medications, or growing children 1. The diagnostic approach should include a comprehensive medical history, physical examination, and additional blood tests such as gamma-glutamyl transferase (GGT), bilirubin, and liver function tests to distinguish between liver and bone sources.
- Key considerations in the diagnostic approach include:
- Measurements of GGT can indicate whether pathologically elevated ALP is of hepatic or nonhepatic origin 1
- Concomitantly elevated GGT can help confirm that an elevated ALP originates from the liver and indicates cholestasis 1
- Imaging studies like ultrasound, CT scans, or bone scans may be necessary depending on the suspected cause
- Treatment focuses on addressing the underlying condition rather than the elevated ALP itself, and the most effective treatment approach will depend on the underlying cause of the elevated ALP, as suggested by the most recent evidence 1. For liver-related elevations, this might involve treating hepatitis, removing obstructions, or discontinuing hepatotoxic medications. For bone-related causes, treatments may include bisphosphonates for Paget's disease or appropriate management of other bone conditions. Regular monitoring of ALP levels is important to track treatment effectiveness.
From the Research
Causes of High Alk Phos
- High levels of alkaline phosphatase activity are characteristic of bone disease with increased osteoblastic activity, hepatobiliary disease with partial or complete biliary obstruction, and transient hyperphosphatasemia in children 2
- The main source of elevated serum alkaline phosphatase activity in the serum of patients with hepatobiliary diseases is the liver isoenzyme 3
- Defective enzyme elimination could play a major role in the pathogenesis of serum alkaline phosphatase elevations 4
Diagnosis and Differentiation
- A gamma-glutamyl transpeptidase is often useful to differentiate whether an elevated alkaline phosphatase originates in the bones or the liver 2
- A serum alkaline phosphatase isozyme pattern by electrophoresis is also necessary to differentiate various pathological states 2
- The isodistribution of the alkaline phosphatase isoenzymes (the bone, liver, and intestinal fraction) in the serum can be studied by the heat inactivation and inhibition method and by electrophoretic separation on agar gel 3
Clinical Significance
- Alkaline phosphatase has a close diagnostic bearing not only on cholestatic forms of hepatobiliary diseases but also on the activity of liver disease 3
- Alkaline phosphatase is involved in the pathogenesis of ectopic calcification, inflammation, metabolic syndrome, vascular calcification, endothelial dysfunction, fibrosis, cardiovascular disease, and mortality 5
- The association between ALP, vitamin K, bone metabolism, and fracture risk in patients with chronic kidney disease (CKD) is also discussed 5
Function and Expression
- Alkaline phosphatase plays a critical function in the formation of hard tissue, increasing inorganic phosphate local rates and facilitating mineralization as well as reducing the extracellular pyrophosphate concentration, an inhibitor of mineral formation 6
- The tissue-nonspecific isozyme of ALP (TNAP) is strongly expressed in bone, liver, and kidney and plays a key function in the calcification of bones 6