From the Guidelines
Alkaline phosphatase (ALP) elevation in non-hepatic conditions is most commonly associated with bone disorders, such as Paget's disease, osteomalacia, rickets, bone metastases, and hyperparathyroidism, as well as pregnancy and certain medications. When evaluating elevated ALP, it's essential to consider the patient's clinical history, medications, and other laboratory results, such as gamma-glutamyl transferase (GGT) or 5'-nucleotidase, to differentiate between hepatic and non-hepatic causes 1. Some key non-hepatic conditions that can cause ALP elevation include:
- Bone disorders: Paget's disease, osteomalacia, rickets, bone metastases, recent fractures, and hyperparathyroidism
- Pregnancy: particularly in the third trimester, due to placental production of ALP
- Gastrointestinal conditions: intestinal ischemia, inflammatory bowel disease, and intestinal perforation
- Growth in children and adolescents: naturally increases ALP levels due to bone formation
- Certain medications: phenytoin, carbamazepine, and trimethoprim-sulfamethoxazole can induce ALP elevation
- Other causes: chronic kidney disease, sepsis, hyperthyroidism, and some malignancies Isoenzyme testing can specifically identify whether the ALP originates from liver, bone, intestine, or placenta, providing crucial diagnostic information when the cause isn't clinically obvious 1. In patients with X-linked hypophosphataemia, ALP levels are a reliable biomarker of rickets activity and osteomalacia, and should be monitored regularly, along with other biochemical parameters such as PTH and urinary calcium levels 1. In general, when evaluating elevated ALP, a comprehensive approach considering the patient's clinical context, laboratory results, and imaging studies is necessary to determine the underlying cause and guide appropriate management.
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 Paget's disease of bone is a chronic, focal skeletal disorder characterized by greatly increased and disorderly bone remodeling Serum alkaline phosphatase, the most frequently used biochemical index of disease activity, provides an objective measure of disease severity and response to therapy. Daily administration of teriparatide to men and postmenopausal women with osteoporosis in clinical studies stimulated bone formation, as shown by increases in the formation markers serum bone-specific alkaline phosphatase (BSAP) and procollagen I carboxy-terminal propeptide (PICP)
Non-hepatic conditions that can cause alkaline phosphatase elevation include:
- Bone disorders, such as osteoporosis, Paget's disease of bone, and osteomalacia
- Bone growth and development, such as in children and adolescents
- Bone remodeling, such as in response to fracture or orthopedic surgery
- Hyperparathyroidism, which can cause increased bone resorption and formation
- Vitamin D deficiency, which can cause increased bone turnover
The use of alendronate and teriparatide can also affect alkaline phosphatase levels, as they are used to treat bone disorders and can influence bone turnover. 2 3
From the Research
Alkaline Phosphatase Elevation in Non-Hepatic Conditions
- Alkaline phosphatase (ALP) is an enzyme that can be elevated in various conditions beyond liver disease, including bone disease, endocrine disease, and neoplasia 4.
- In the context of Paget's disease of bone, ALP elevation is a common feature, and treatment with bisphosphonates can help reduce ALP levels and alleviate symptoms 5, 6, 7.
- Bisphosphonates, such as alendronate and risedronate, have been shown to be effective in reducing ALP levels and improving bone pain in patients with Paget's disease 5, 6, 7, 8.
- Non-hepatic conditions that can cause ALP elevation include:
- Bone disease, such as Paget's disease or osteomalacia
- Endocrine disorders, such as hyperthyroidism or hypothyroidism
- Neoplasia, such as bone cancer or lymphoma
- Pregnancy and lactation
- High-fat diets
- Certain drugs, such as glucocorticoids and anticonvulsants 4
- It is essential to consider these non-hepatic conditions when interpreting ALP elevation in patients, as they may require different diagnostic and therapeutic approaches 4.