What is the management for chronic alkaline phosphatase (Alk Phos) elevation?

From the Guidelines

Chronic alkaline phosphatase (Alk Phos) elevation should be managed by first identifying the underlying cause through a systematic diagnostic approach, focusing on liver-related causes such as intrahepatic cholestasis of pregnancy or primary sclerosing cholangitis (PSC), and then treating the specific condition rather than the Alk Phos elevation itself. The diagnostic approach should include a comprehensive medical history, physical examination, and laboratory tests to determine if the elevation is from hepatic, bone, or other origins. Liver-related causes should be investigated with liver function tests, hepatitis serologies, and imaging studies like ultrasound or CT scan, as well as magnetic resonance cholangiopancreaticography (MRCP) for suspected PSC 1. For bone-related causes, consider vitamin D levels, parathyroid hormone, calcium, and phosphate measurements, along with bone scans if indicated.

Key considerations in the diagnostic process include:

• Evaluating for intrahepatic cholestasis of pregnancy in pregnant women with pruritus and elevated serum bile acid levels >10 mmol/L, and treating with ursodeoxycholic acid (10-15 mg/kg/day) 1
• Investigating for PSC in patients with persistently elevated serum liver tests in a cholestatic pattern, using MRCP as a diagnostic tool, and considering the presence of inflammatory bowel disease (IBD) 1
• Assessing for other liver diseases, such as primary biliary cholangitis, and treating accordingly with ursodeoxycholic acid (13-15 mg/kg/day)
• Correcting vitamin D deficiency with supplementation (typically 1000-2000 IU daily) if bone-related causes are identified

Regular monitoring of Alk Phos levels every 3-6 months is recommended to assess treatment response. The management approach is guided by the pathophysiology that Alk Phos is an enzyme produced by multiple tissues, and its elevation reflects underlying tissue damage or increased cellular activity rather than being a primary disorder itself.

From the FDA Drug Label

In clinical trials, alendronate sodium 40 mg once daily for six months produced significant decreases in serum alkaline phosphatase as well as in urinary markers of bone collagen degradation. Re-treatment with alendronate sodium tablets, may be considered, following a six-month post-treatment evaluation period in patients who have relapsed, based on increases in serum alkaline phosphatase, which should be measured periodically 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 In osteoporosis treatment studies alendronate sodium 10 mg/day decreased the markers of bone formation, osteocalcin and bone specific alkaline phosphatase by approximately 50%, and total serum alkaline phosphatase by approximately 25 to 30% to reach a plateau after 6 to 12 months

The management for chronic alkaline phosphatase (Alk Phos) elevation may include treatment with alendronate sodium, which has been shown to decrease serum alkaline phosphatase levels in clinical trials 2.

• The recommended dosage for treatment of Paget's disease is 40 mg once daily for six months 2.
• Re-treatment may be considered after a six-month post-treatment evaluation period in patients who have relapsed, based on increases in serum alkaline phosphatase 2.
• Alendronate sodium has also been shown to reduce bone-specific alkaline phosphatase and total serum alkaline phosphatase in patients with osteoporosis and glucocorticoid-induced osteoporosis 2 2. Key points to consider when managing chronic Alk Phos elevation with alendronate sodium include:
• Monitoring serum alkaline phosphatase levels periodically to assess response to treatment
• Considering re-treatment after a six-month post-treatment evaluation period in patients who have relapsed
• Adjusting the dosage and duration of treatment based on the individual patient's response and underlying condition 2 2 2.

From the Research

Chronic Alkaline Phosphatase Elevation Management

Chronic alkaline phosphatase (Alk Phos) elevation can be caused by various conditions, including bone and liver diseases, malignancies, and benign conditions. The management of chronic Alk Phos elevation depends on the underlying cause.

Possible Causes

• Bone involvement from malignancy or Paget's disease 3
• Sepsis, including gram-negative and gram-positive organisms, and fungal sepsis 3
• Biliary obstruction, including malignant obstruction and common bile duct stones 3
• AIDS and related infections, such as mycobacterium avium intracellulare (MAI) and cytomegalovirus 3
• Diffuse liver metastases 3
• Benign intrahepatic disease, including liver hemangiomas, sarcoid hepatitis, and drug-induced cholestasis 3
• Primary biliary cirrhosis, which can be treated with ursodeoxycholic acid 4
• Benign familial hyperphosphatasemia, a genetic condition with elevated intestinal alkaline phosphatase levels 5

Diagnostic Approach

• Evaluate the patient's medical history, physical examination, and laboratory results to determine the underlying cause of the Alk Phos elevation
• Consider further testing, such as imaging studies, liver biopsy, or bone scan, to confirm the diagnosis
• In some cases, a normal Alk Phos level does not rule out primary biliary cholangitis, and other biomarkers, such as gamma-glutamyl transferase (GGT), may be useful in diagnosis 6

Treatment

• Treatment of the underlying cause of the Alk Phos elevation, such as antibiotics for sepsis or ursodeoxycholic acid for primary biliary cirrhosis
• Monitoring of liver function tests and other relevant laboratory results to assess the effectiveness of treatment
• Consideration of referral to a specialist, such as a hepatologist or rheumatologist, for further evaluation and management

Prognosis

• The prognosis for patients with chronic Alk Phos elevation depends on the underlying cause and the effectiveness of treatment
• In some cases, such as primary biliary cirrhosis, timely initiation of treatment can prevent progression to cirrhosis and liver failure 6
• In other cases, such as malignancy or diffuse liver metastases, the prognosis may be poorer, and treatment may be focused on palliation and symptom management 7