Can Losartan (losartan) cause hypophosphatasia (low alkaline phosphatase levels)?

Losartan and Low Alkaline Phosphatase (Hypophosphatasia)

There is no evidence in the medical literature that losartan causes low alkaline phosphatase levels (hypophosphatasia). The available guidelines and research do not establish any connection between losartan use and decreased alkaline phosphatase activity.

Understanding Hypophosphatasia

Hypophosphatasia (HPP) is a rare inherited disorder characterized by:

• Low serum alkaline phosphatase (ALP) levels (<30 IU/L) 1
• Impaired primary mineralization of osteoid (osteomalacia) 1
• Elevated levels of phosphorylated metabolites, including:
  • Pyridoxal-5'-phosphate (PLP/vitamin B6) 2
  • Phosphoethanolamine
  • Pyrophosphate

HPP is caused by pathogenic variants in the ALPL gene, which encodes tissue non-specific alkaline phosphatase 3. The condition can present with:

• Skeletal pain
• Chondrocalcinosis
• Calcific periarthritis
• Dental problems
• Stress fractures and atypical fractures
• Fragility fractures

Losartan's Known Side Effects

Losartan, an angiotensin II receptor blocker (ARB), has several documented side effects, but hypophosphatasia is not among them:

• Hyperkalemia (elevated potassium levels), especially in patients with kidney disease, diabetes, or when combined with other medications that raise potassium 4
• Dizziness (most common drug-related adverse effect) 5
• Rare cases of angioedema (similar to ACE inhibitors) 5
• Increased uric acid secretion and lowered plasma uric acid levels 5

Diagnostic Considerations for Low ALP

If a patient on losartan presents with low ALP levels, consider:

1. Genetic testing for ALPL gene mutations to confirm hypophosphatasia 3
2. Measurement of ALP substrates including:
   • Pyrophosphate
   • Pyridoxal phosphate (vitamin B6)
   • Phosphoethanolamine 3
3. Evaluate for other causes of low ALP:
   • Malnutrition
   • Vitamin and mineral deficiencies
   • Endocrine disorders
   • Certain medications (particularly antiresorptives, but not ARBs) 3
   • Severe acute injuries or diseases 3

Important Clinical Considerations

• Low ALP was found in 9% of patients attending osteoporosis clinics, but this was not associated with ARB use 1
• Hypophosphatasia may be misdiagnosed as osteoporosis, leading to inappropriate treatment with antiresorptive therapy 1
• In some cases, bone-specific ALP may be low while total ALP remains normal 6

Conclusion

Based on the available evidence, there is no established causal relationship between losartan and low alkaline phosphatase levels. If a patient on losartan presents with low ALP, consider alternative causes such as genetic hypophosphatasia or other conditions that can decrease ALP levels.