From the Guidelines
When evaluating a patient with elevated alkaline phosphatase (ALP) but normal calcium and hepatic enzymes, the initial approach should focus on determining if the ALP elevation is of bone or non-hepatic origin by measuring ALP isoenzymes to identify the source tissue. This approach is crucial as elevated ALP can be due to various conditions, including bone diseases like Paget's disease, osteomalacia, bone metastases, or healing fractures, as well as cholestatic liver disease 1. The measurement of ALP isoenzymes helps differentiate between hepatic and non-hepatic causes, with gamma-glutamyl transpeptidase (GGT) levels also aiding in this distinction, as GGT is not found in bone but is present in the liver and other tissues 1. Key considerations in the evaluation include:
- A thorough history and physical examination focusing on bone pain, recent fractures, malignancy history, or medication use, particularly those affecting bone metabolism.
- Laboratory tests such as vitamin D levels, parathyroid hormone (PTH), phosphate, and a complete metabolic panel to assess bone health and metabolism.
- Imaging studies, starting with plain radiographs of symptomatic areas, followed by bone scans if needed, to detect areas of increased bone turnover. In cases where the diagnosis remains unclear after initial evaluation, consideration should be given to referral to an endocrinologist or rheumatologist for further evaluation and management. This systematic approach, guided by the most recent evidence 1, helps identify the underlying cause of isolated ALP elevation, allowing for appropriate targeted treatment of the specific disorder, whether of bone or non-hepatic origin, thus prioritizing the patient's morbidity, mortality, and quality of life.
From the Research
Evaluation Approach for Elevated Alkaline Phosphatase
The evaluation approach for a patient with elevated alkaline phosphatase (ALP) and normal calcium levels, as well as normal hepatic enzymes, involves considering various potential causes.
- The patient's medical history, physical examination, and laboratory tests are essential in determining the underlying cause of elevated ALP 2.
- Bone disease is a common cause of elevated ALP, particularly in postmenopausal women, where high bone turnover is a significant contributor 3.
- Other potential causes of elevated ALP include malignancy, Paget's disease of bone, and secondary hyperparathyroidism 4, 5.
- In some cases, elevated ALP can be associated with sepsis, biliary obstruction, or AIDS 6.
Diagnostic Considerations
- Laboratory tests, such as bone-specific alkaline phosphatase (BAP) and other bone metabolic markers, can help identify the source of elevated ALP 3.
- Imaging studies, like X-rays or bone scans, may be necessary to evaluate bone health and detect potential abnormalities 4.
- A thorough medical history and physical examination can help identify underlying conditions that may be contributing to elevated ALP 2, 6.
Treatment and Management
- Treatment of the underlying cause of elevated ALP is crucial in managing the condition 4, 5.
- Bisphosphonate therapy may be effective in reducing ALP levels in patients with high bone turnover or Paget's disease of bone 4, 3.
- Active vitamin D therapy may also play a role in managing secondary hyperparathyroidism and potentially Paget's disease 5.