From the Guidelines
Elevated alkaline phosphatase (Alk Phos) levels can result from various conditions, including liver diseases such as cholestatic liver disease, primary biliary cholangitis, and primary sclerosing cholangitis, as well as bone diseases like Paget's disease and osteomalacia, as noted in a recent study 1.
Causes of Elevated Alk Phos
The causes of elevated Alk Phos can be broadly categorized into liver-related and bone-related conditions. Liver-related causes include:
- Cholestatic liver disease, such as primary biliary cholangitis and primary sclerosing cholangitis
- Bile duct obstruction, choledocholithiasis, and malignant obstruction
- Infiltrative liver diseases, such as sarcoidosis and amyloidosis
- Hepatitis, cirrhosis, and congestive heart failure Bone-related causes include:
- Paget's disease
- Osteomalacia
- Hyperparathyroidism
- Bone metastases
- Healing fractures and bone growth in children and adolescents Other conditions that can raise Alk Phos include pregnancy, certain cancers, heart failure, inflammatory bowel disease, sepsis, and hyperthyroidism.
Diagnosis and Treatment
When Alk Phos is elevated, doctors typically order additional tests to determine the source, including gamma-glutamyl transferase (GGT) to distinguish between liver and bone sources, liver function tests, and sometimes imaging studies, as recommended in a recent guideline 1. The pattern of elevation and accompanying symptoms help guide diagnosis and treatment of the underlying cause. A diagnosis of large duct primary sclerosing cholangitis (PSC) should be made in the presence of typical findings of sclerosing cholangitis on high-quality cholangiography and after exclusion of secondary causes, with magnetic resonance cholangiopancreaticography (MRCP) being the preferred diagnostic test 1.
From the Research
Causes of Elevated Alkaline Phosphatase (Alk Phos)
- Paget's disease of bone, a common destructive condition of bone that affects 1-2% of the population, most typically those over the age of 55 years, can cause an isolated elevation of serum alkaline phosphatase 2
- Bone disease, such as Paget's disease, can result in increased alkaline phosphatase activity, with bone alkaline phosphatase (BAP) being increased in the serum of patients with Paget's disease 3
- Nonhepatic increases in serum alkaline phosphatase activity can be found in young animals, in pregnant and lactating females, and in association with high fat diets, as well as in bone disease, endocrine disease, neoplasia, and other disorders 4
- Circulating and tissue-derived isoforms of bone alkaline phosphatase, such as B/I, B1, and B2, can be increased in Paget's disease of bone, with the B2 isoform having the greater relative activity 5
- Alkaline phosphatase can also be involved in the pathogenesis of ectopic calcification, inflammation, metabolic syndrome, vascular calcification, endothelial dysfunction, fibrosis, cardiovascular disease, and mortality, particularly in patients with chronic kidney disease (CKD) 6