From the Guidelines
Intermittent isolated elevations in alkaline phosphatase (ALP) should be thoroughly evaluated to identify the underlying cause, with a focus on liver and bone disorders, as well as normal physiologic variations. The most recent and highest quality study, 1, suggests that ALP elevations can be indicative of liver damage, particularly in the context of cholestatic liver disease. When evaluating intermittent isolated ALP elevations, the following steps should be taken:
- Confirm the elevation with repeat testing and check for patterns in the fluctuations
- Perform a comprehensive metabolic panel to assess liver function
- Measure GGT levels to determine if the ALP is of liver or bone origin
- Consider liver ultrasound if liver pathology is suspected
- Evaluate bone-specific ALP or vitamin D levels if bone pathology is suspected
- Review medications, as certain drugs can cause ALP elevations, as noted in 1 If the elevation is mild (less than 2-3 times the upper limit of normal) and the patient is asymptomatic with no other abnormal liver tests, watchful waiting with periodic monitoring may be appropriate, as suggested by 1. However, persistent or significant elevations warrant referral to a gastroenterologist or hepatologist for further evaluation, as recommended by 1. The clinical significance of isolated ALP elevation depends on its magnitude, persistence, and the patient's overall clinical picture, highlighting the importance of a thorough medical workup, as emphasized in 1 and 1.
From the Research
Causes of Intermittent Isolated Alk Phos Elevation
- The most common causes of isolated elevated alkaline phosphatase (ALP) levels include underlying malignancy, bone disease, and unsuspected parenchymal liver disease 2
- A study found that 57% of patients with isolated elevated ALP levels had underlying malignancy, with 61 patients having infiltrative intrahepatic malignancy, 52 patients having bony metastasis, and 34 patients having both hepatic and bone metastasis 2
- Bone disease accounted for 29% of the cases, with Paget's disease of bone being a possible cause 2, 3, 4, 5
Clinical Significance of Isolated Alk Phos Elevation
- Isolated elevated ALP levels can be associated with a variety of medical illnesses and often normalize within months 6
- Persistent ALP elevations are usually associated with a clinically obvious diagnosis, such as terminal malignancies or bone disease 6, 2
- A reasonable approach to patients with isolated ALP elevation is a careful history, physical exam, and routine lab studies to detect obvious diagnoses, followed by repeat enzyme determination at 1-3 months 6
Treatment of Underlying Conditions
- Bisphosphonates are the mainstay of treatment for Paget's disease of bone, with zoledronate being an attractive option due to its high rates of biochemical remission and long duration of suppression 3, 4, 5
- Treatment with bisphosphonates can improve pain in people with Paget's disease of bone, but the evidence for other benefits is limited 4
- Vitamin D and calcium supplements should be given to patients at risk of vitamin D insufficiency when given zoledronate to prevent symptomatic hypocalcemia 5