Possible causes of increased levels of plasma alkaline phosphatase include:

• hepatobiliary disease including:
• cholestasis: increased synthesis of hepatocyte ALP and increased secretion of high molecular weight form into plasma; elevations of ALP of up to 10 times normal levels
• hepatocyte disease, such as viral hepatitis which cause moderate elevations in ALP
• bone disease - bone isoenzyme of alkaline phosphatase, reflecting increased osteoblastic activity, may be raised in:
• Paget's disease
• osteomalacia and rickets
• renal osteodystrophy
• bone metastases
• primary bone tumour e.g. sarcoma
• recent fracture
• growing child - especially at puberty
• during pregnancy the placenta secretes its own isoenzyme which raises total alkaline phosphatase concentration
• malignancies resulting in expression of ALP-like gene e.g. seminomas

In determining whether a raised ALP is of hepatic or bony origin e.g. in metastasis of breast cancer, the following may be useful:

• other test of hepatic function e.g. GGT
• electrophoresis separation of isoenzymes
• bone scan
• ultrasound scan of liver