What are the causes of elevated alkaline phosphatase (alk phos)?

From the Guidelines

Elevated alkaline phosphatase (ALP) is most commonly caused by liver disorders, such as cholestatic liver disease, and bone diseases, including Paget's disease and osteomalacia, as well as certain medications and physiological conditions like pregnancy. The causes of elevated ALP can be broadly categorized into liver and non-liver (bone) sources. In liver conditions, cholestasis, which is the impairment of bile flow, can lead to elevated ALP levels, as seen in conditions like primary biliary cholangitis, primary sclerosing cholangitis, and bile duct obstruction 1. Bone-related causes include conditions with increased bone turnover, such as Paget's disease, osteomalacia, and hyperparathyroidism, where more ALP is released into the bloodstream 1. Pregnancy is also a physiological condition that can elevate ALP levels due to placental production 1. Certain medications, like phenytoin and statins, can raise ALP levels as well 1. Other causes include inflammatory bowel disease, sepsis, hyperthyroidism, and some cancers. When investigating the cause of elevated ALP, additional tests such as gamma-glutamyl transferase (GGT) are used to distinguish between liver and bone sources, alongside liver function tests, imaging studies, and sometimes bone-specific ALP isoenzymes 1. The most recent and highest quality study, from 2023, emphasizes the importance of considering both liver and bone diseases in the differential diagnosis of elevated ALP, and utilizing imaging techniques like MRCP for the diagnosis of conditions such as primary sclerosing cholangitis 1. Key points to consider in the evaluation of elevated ALP include:

• Clinical presentation, such as symptoms of cholestasis (jaundice, pruritus) or bone pain
• Laboratory tests, including GGT, liver function tests, and bone-specific ALP isoenzymes
• Imaging studies, such as MRCP, to evaluate the biliary tree and liver parenchyma
• Physiological conditions, like pregnancy, and medication use that could elevate ALP levels. Given the potential for significant morbidity and mortality associated with untreated liver and bone diseases, prompt and thorough evaluation of elevated ALP is crucial to determine the underlying cause and guide appropriate treatment, which may include addressing liver disease, managing bone disorders, or adjusting medications 1.

From the Research

Elevated Alk Phos Causes

Elevated alkaline phosphatase (alk phos) levels can be caused by various conditions, including:

• Bone disorders such as Paget's disease, which is characterized by disorganized bone remodeling 2, 3, 4
• Liver disease, although in some cases, bone alkaline phosphatase (BAP) may be normal while total alkaline phosphatase (TAP) is elevated 2
• Other conditions that affect bone cell function and skeletal status

Paget's Disease and Alk Phos

In Paget's disease, elevated alk phos levels are often seen, and the level of alkaline phosphatase correlates with disease activity 3, 4

• The measurement of bone-specific proteins such as BAP can provide useful information in assessing skeletal status and diagnosing Paget's disease 2
• Bisphosphonate therapy is often used to treat Paget's disease, and it can lead to a sustained reduction in bone pain and markers of bone turnover 3, 4

Evaluation of Paget's Disease Activity

The activity of Paget's disease can be evaluated by measuring alkaline phosphatase levels, although this may underestimate the activity of Pagetic bone in localized forms of the disease 5

• Other tests such as urinary hydroxyproline and 45Ca kinetic studies can also be used to evaluate disease activity 5
• Treatment should be considered for patients with localized forms of the disease that have a high risk of functional impairment or other complications 5