From the Guidelines
Elevated Alkaline Phosphatase (ALP) levels are primarily caused by liver or bone disorders, and a comprehensive medical history, physical examination, and additional laboratory tests such as gamma-glutamyl transferase (GGT), bilirubin, transaminases, calcium, phosphate, and vitamin D levels are necessary to determine the underlying cause. The most recent and highest quality study 1 suggests that ALP is produced mainly in the liver and is present in the canalicular membrane of the hepatocyte, and is also found in bone and in smaller amounts in the intestines, kidneys, and white blood cells.
Common Causes of Elevated ALP
- Liver disorders:
- Cholestatic liver disease, such as primary biliary cholangitis, primary sclerosing cholangitis, intrahepatic or extrahepatic bile duct obstruction, and drug-induced cholestasis
- Cirrhosis, chronic hepatitis, viral hepatitis, congestive heart failure (hepatic congestion), and ischemic cholangiopathy
- Bone disorders:
- Paget’s disease, bony metastases, or fracture
- Osteomalacia, hyperparathyroidism
Diagnostic Approach
- Measurements of GGT can indicate whether pathologically elevated ALP is of hepatic or nonhepatic origin
- Concomitantly elevated GGT can help confirm that an elevated ALP originates from the liver and indicates cholestasis
- Imaging of the biliary tree may be necessary to determine the etiology of extrahepatic or intrahepatic cholestasis
Management
- Depends on the underlying cause
- Biliary obstruction may require surgical intervention
- Paget's disease might be treated with bisphosphonates such as alendronate 70mg weekly or zoledronic acid 5mg IV annually
- Isolated mild ALP elevations (less than 2-3 times the upper limit of normal) without symptoms may warrant monitoring rather than immediate intervention, as suggested by 1 and 1.
From the FDA Drug Label
Serum alkaline phosphatase, the most frequently used biochemical index of disease activity, provides an objective measure of disease severity and response to therapy. Paget's disease of bone is a chronic, focal skeletal disorder characterized by greatly increased and disorderly bone remodeling Excessive osteoclastic bone resorption is followed by osteoblastic new bone formation, leading to the replacement of the normal bone architecture by disorganized, enlarged, and weakened bone structure.
The causes of elevated Alkaline Phosphatase (ALP) levels include:
- Paget's disease of bone, a chronic skeletal disorder characterized by increased and disorderly bone remodeling
- Excessive osteoclastic bone resorption followed by osteoblastic new bone formation 2