From the Guidelines
Elevated alkaline phosphatase (ALP) is a significant laboratory finding that warrants further investigation as it may indicate several underlying health conditions, particularly liver disorders such as bile duct obstruction, hepatitis, cirrhosis, or liver cancer, and bone diseases like Paget's disease, osteomalacia, or bone tumors, as noted in the most recent study 1. Elevated ALP is a nonspecific finding that can occur in various conditions, and its significance depends on the level of elevation, presence of other symptoms, and laboratory abnormalities.
- Common causes of elevated ALP include liver disorders, bone diseases, certain medications, pregnancy, or growing children with naturally higher levels due to bone growth.
- To determine the specific cause, additional testing is typically necessary, including gamma-glutamyl transferase (GGT) or 5'-nucleotidase to distinguish between liver and bone sources, liver function tests, imaging studies, or bone-specific ALP isoenzymes, as recommended in the study 1.
- Management focuses on treating the underlying condition rather than the elevated ALP itself, which is considered a marker rather than a disease.
- The study 1 also highlights the importance of considering primary sclerosing cholangitis (PSC) in patients with elevated serum markers of cholestasis, particularly in those with concomitant inflammatory bowel disease (IBD).
- Furthermore, the study 1 notes that early increases in serum bone-specific alkaline phosphatase (B-ALP) levels have been shown to predict short skeletal-related event (SRE)-free survival and reduced overall survival (OS) in patients with prostate cancer and bone metastases.
- In summary, elevated ALP is a significant finding that requires further investigation to determine the underlying cause, and management should focus on treating the underlying condition, as emphasized in the most recent study 1.
From the Research
Significance of Elevated Alkaline Phosphatase
Elevated alkaline phosphatase (ALP) levels can be indicative of various diseases, primarily affecting the skeleton and the biliary tract 2. The measurement of total ALP activity in serum or plasma is a useful biomarker in clinical practice, with raised or reduced values suggesting a number of diseases.
Clinical Implications
- Elevated ALP levels can be found in multiple hepatobiliary diseases and in bone diseases, and can also originate in the intestine and placenta 3.
- In the evaluation of elevated ALP, most patients will not require determination of its isoenzymes, but it is important to be aware of benign familial intestinal hyperphosphatasemia (BFIH) to avoid unnecessary additional studies 3.
- Electrophoretic assays are preferable for visualizing and investigating the cause of increased serum total ALP activities, and bone ALP immunoassays are preferable for investigating and monitoring individuals with bone and mineral metabolic abnormalities 2.
Association with Cardiovascular Disease
- Elevated levels of serum ALP are associated with an increased risk of cardiovascular disease (CVD), coronary heart disease (CHD), and stroke, as well as their subtypes, among men and women 4.
- Higher ALP levels, even within the normal range, are significantly associated with increased risks of CVD, in a dose-dependent manner 4.
- Regular monitoring of ALP levels may help in improving the early identification of the population at higher CVD risk 4.