From the Guidelines
Elevated alkaline phosphatase (ALP) levels often indicate liver disease or bone disorders, and further testing, including gamma-glutamyl transferase (GGT) and imaging studies, is recommended to determine the underlying cause. Alkaline phosphatase is an enzyme found throughout the body, primarily in the liver, bones, intestines, and placenta 1. Normal adult ALP levels typically range from 20-140 IU/L, though reference ranges vary by laboratory.
Key Points to Consider
- Elevated ALP levels can occur in a variety of conditions affecting the liver, including cirrhosis, chronic hepatitis, viral hepatitis, congestive heart failure, and ischemic cholangiopathy 1.
- Pathologically increased levels of ALP may also occur in bone disease, such as Paget’s disease, bony metastases, or fracture 1.
- Measurements of GGT can indicate whether pathologically elevated ALP is of hepatic or nonhepatic origin 1.
- Concomitantly elevated GGT can help confirm that an elevated ALP originates from the liver and indicates cholestasis 1.
- Imaging of the biliary tree may be necessary to determine the etiology of extrahepatic or intrahepatic cholestasis 1.
- In patients with primary sclerosing cholangitis (PSC), markedly elevated serum ALP activity is consistently associated with worse prognosis 1.
- However, ALP cannot be recommended as a standalone surrogate marker due to its naturally fluctuating course in PSC and varying predictive cut-off values across studies 1.
- Non-invasive evaluation of liver fibrosis, such as liver stiffness measurement (LSM) by vibration-controlled transient elastography (VCTE) or the serum enhanced liver fibrosis (ELF) test, may be useful in predicting outcomes and guiding management in patients with PSC 1.
From the FDA Drug Label
Alendronate decreases bone resorption without directly inhibiting bone formation In clinical studies of up to two years' duration, alendronate sodium 5 and 10 mg/day reduced cross-linked N-telopeptides of type I collagen (a marker of bone resorption) by approximately 60% and reduced bone-specific alkaline phosphatase and total serum alkaline phosphatase (markers of bone formation) by approximately 15 to 30% and 8 to 18%, respectively Treatment of men with osteoporosis with alendronate sodium 10 mg/day for two years reduced urinary excretion of cross-linked N-telopeptides of type I collagen by approximately 60% and bone-specific alkaline phosphatase by approximately 40%. Serum alkaline phosphatase, the most frequently used biochemical index of disease activity, provides an objective measure of disease severity and response to therapy. Alendronate sodium decreases the rate of bone resorption directly, which leads to an indirect decrease in bone formation
Alendronate sodium reduces alkaline phosphatase levels. The reduction in alkaline phosphatase levels is a result of the inhibition of bone resorption and the subsequent decrease in bone formation.
- The reduction in bone-specific alkaline phosphatase is approximately 40% in men with osteoporosis treated with alendronate sodium 10 mg/day for two years 2.
- The reduction in total serum alkaline phosphatase is approximately 8 to 18% in clinical studies of up to two years' duration with alendronate sodium 5 and 10 mg/day 2.
From the Research
Alkaline Phosphatase in Paget's Disease
- Alkaline phosphatase (ALP) is a key marker in the diagnosis and management of Paget's disease of bone (PDB) 3, 4, 5, 6, 7
- Serum total alkaline phosphatase (ALP) is recommended as a first-line biochemical screening test in combination with liver function tests in screening for the presence of metabolically active PDB 3
- Bone alkaline phosphatase (BAP) is increased in the serum of patients with Paget's disease and correlates better with total AP than with bone Gla protein (BGP) 4
- BAP measurements by immunoassay offer a novel method of assessing skeletal status and provide information that is separately useful in assessing the skeleton for a variety of metabolic bone diseases 4
- An elevated serum alkaline phosphatase level correlates with the disease activity in Paget's disease 7
Diagnosis and Treatment
- The diagnosis of Paget's disease is confirmed by characteristic radiographic findings and by nuclear scintigraphy of the bone (the most sensitive test) 7
- Bisphosphonates, such as zoledronic acid, pamidronate, alendronate, and risedronate, are the mainstay of treatment for Paget's disease 5, 7
- Treatment aimed at improving symptoms is recommended over a treat-to-target strategy aimed at normalizing total ALP in PDB 3
- Patients who do not tolerate bisphosphonates can be treated with calcitonin 7
Evaluation of Disease Activity
- The alkaline phosphatase level (AP) is a measure of the phosphatase activity throughout the skeleton, but it under-estimates the activity of Pagetic bone in localized forms of the disease 6
- To accurately evaluate the activity of Pagetic bone, the value of AP needs to be expressed in terms of the percentage of bone tissue affected by the disease 6