From the Guidelines
Elevated alkaline phosphatase (ALP) levels are commonly caused by liver disorders, bone diseases, pregnancy, and certain medications, and management depends on identifying and treating the underlying cause rather than treating the elevated ALP itself. Liver causes include biliary obstruction, hepatitis, cirrhosis, and infiltrative diseases, while bone-related causes include Paget's disease, osteomalacia, bone metastases, and fracture healing 1.
Causes of Elevated ALP
- Liver disorders: biliary obstruction, hepatitis, cirrhosis, and infiltrative diseases
- Bone diseases: Paget's disease, osteomalacia, bone metastases, and fracture healing
- Pregnancy and certain medications can also cause elevated ALP levels
- Other causes include cholestatic liver disease, primary biliary cholangitis, primary sclerosing cholangitis, and drug-induced cholestasis 1
Management of Elevated ALP
- Identify and treat the underlying cause of elevated ALP
- For liver disease, this may involve removing biliary obstructions, treating hepatitis, or discontinuing hepatotoxic medications
- For bone disorders, treatment might include bisphosphonates for Paget's disease, vitamin D supplementation for osteomalacia, or cancer treatments for bone metastases 1
- During evaluation, it's essential to check for patterns of other liver enzymes and consider ALP isoenzymes to determine the source tissue
Evaluation and Monitoring
- Isolated ALP elevation without symptoms sometimes requires only monitoring
- Persistent unexplained elevations warrant comprehensive investigation, including imaging studies of the liver and biliary system 1
- The normal ALP range varies by age, sex, and laboratory standards, with higher values typically acceptable in children, adolescents, and pregnant women due to bone growth and placental production 1
From the Research
Causes of Elevated Alkaline Phosphatase (Alk Phos) Levels
- Paget's disease of bone, a common bone disorder characterized by disorganized bone remodeling, is a cause of elevated alkaline phosphatase levels 2
- Secondary hyperparathyroidism, often seen in patients with chronic renal disease, can also lead to elevated alkaline phosphatase levels 3
- Other conditions such as osteomalacia, bone fractures, and osteoarthritis may also contribute to elevated alkaline phosphatase levels
Management of Elevated Alkaline Phosphatase Levels
- Bisphosphonates, such as zoledronic acid, pamidronate, alendronate, and risedronate, are the mainstay of treatment for Paget's disease of bone 2, 4
- Treatment with active vitamin D may also be beneficial in patients with secondary hyperparathyroidism 3
- Correction of hypovitaminosis D with cholecalciferol treatment may improve quality of life in patients with Paget's disease of bone 5
- Radionuclide bone scans and serum total alkaline phosphatase tests are recommended for diagnosing and monitoring Paget's disease of bone 4
Treatment Considerations
- Patients with Paget's disease of bone should be monitored for mineralization defects and hypocalcemia, particularly when treated with bisphosphonates 6
- Serum calcium and vitamin D deficiency should be restored before bisphosphonate treatment, and calcium and vitamin D administration should be continued for longer after achieving normocalcemia 6
- Total hip or knee replacements may be recommended for patients with Paget's disease of bone who develop osteoarthritis and do not respond to medical treatment 4