6 Causes of Low Alkaline Phosphatase in Lupus Patients: Doctor Explains

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Low alkaline phosphatase levels in patients with lupus can occur due to various causes. Commonly, medications, malnutrition, zinc & magnesium deficiency, hypothyroidism, severe anemia associated with lupus, and others.

Today, we will discuss the common causes of low alkaline phosphatase in patients with lupus.

Introduction: essential facts about alkaline phosphatase.

Alkaline phosphatase is an enzyme in many forms in different tissues of your body.

It is important for bone health, cell growth, and protein synthesis and is essential for the fetus’s health during pregnancy (reference).

Four types of alkaline phosphatase are present.

A. Tissue nonspecific ALP (TNS-ALP): It is the main type of alkaline phosphatase. It is present in many tissues, such as:

  • Liver tissues.
  • Bones.
  • Kidneys.
  • And others.

B. Intestinal alkaline phosphatase: in the intestinal tract, mainly the small intestine).

C. Placental alkaline phosphatase: released from the placenta during pregnancy. It causes physiological elevations in alkaline phosphatase, especially during the last trimester.

D. Germ cell alkaline phosphatase: presents mainly in testicles and thymus.

Elevations in alkaline phosphatase are more common than in low alkaline phosphatase.

The most common causes of alkaline phosphatase elevations are liver and bone diseases. Also, many physiological and benign conditions cause elevations in alkaline phosphatases, such as pregnancy, bone growth during childhood and teenager, etc.

Although there is no such data in research about the links between

Low alkaline phosphatase is rare. Today, you will learn the possible causes of low alkaline phosphatase in patients with lupus.

What are the normal reference ranges of alkaline phosphatase?

The normal reference ranges for alkaline phosphatase may vary between different laboratories.

An alkaline phosphatase level between 44-121 in adult males and females is considered normal.

Any alkaline phosphatase levels below the lower limit of normal are considered low. However, clinically significant low alkaline phosphatase in adults is often below 30 U/L.

Refer to the reference ranges provided by your specific laboratory.

Also, the lower limit of alkaline phosphatase differs according to age (the lower limit of normal is often higher in children and young adolescents.

The table below illustrates the lower limits of normal alkaline phosphatase by age and gender (reference).

lower limits of normal alkaline phosphatase


What are the possible causes of low alkaline phosphatase in lupus patients?

1. Drug-induced low alkaline phosphatase with lupus.

Many drugs may cause low alkaline phosphatase levels in patients with lupus. So the first thing your doctor will search for is drugs that may affect alkaline phosphatase activity.

Common drugs that may be used by lupus patients and cause low alkaline phosphatase include:

  • Azathioprine.
  • Cinacalcet.
  • Oral contraception.
  • Vitamin D overdose.

Patients with lupus sometimes use the above medications. Review the list of drugs with your doctor.

Don’t discontinue any drug without the permission of your doctor. The hazards of stopping the medications may exceed the benefits.

2. Malnutrition & protein-free or very low protein in the diet.

Patients with severe lupus may pass through periods of malnutritions as with:

  • During the periods of flare-ups of lupus.
  • Very low protein diet in patients with lupus kidney disease.
  • Anorexia, nausea, and vomiting are associated with lupus.
  • Drugs that cause GI disturbances with lupus result in low caloric intake (such as mycophenolate mofetil).

Malnutrition is a common cause of low alkaline phosphatase levels (reference). For example, females with anorexia nervosa often have low alkaline phosphatase levels due to malnutrition.

3. Magnesium deficiency.

Magnesium deficiency is common among patients with systemic lupus erythematosus and other autoimmune diseases (reference).

Magnesium deficiency may lead to significantly low alkaline phosphatase levels (reference).

So, checking the serum magnesium levels in lupus patients with low alkaline phosphatase levels may help.

4. Zinc deficiency.

Zinc deficiency is also one of the common causes of low alkaline phosphatase in patients with lupus.

Patients with lupus are more susceptible to nutritional deficiencies such as zinc due to poor appetite, medications, and poor absorption of nutrients.

5. Anemia (common in lupus).

Low alkaline phosphatase levels are found in patients with:

  • Pernicious anemia (due to the lack of vitamin B12 absorption).
  • Severe cases of anemia.

Both conditions (especially severe anemia) may be found in some patients with lupus and lead to low alkaline phosphatase levels.

6. Hypothyroidism.

About 15% to 19% of patients with systemic lupus erythematosus have an underactive thyroid (hypothyroidism) (reference).

Hypothyroidism is the most common thyroid disease in patients with lupus.

Some (not all) patients with lupus and underactive thyroid may have low alkaline phosphatase levels.

So, a thyroid functions test (such as TSH) is often needed to exclude thyroid diseases in patients with unexplained low alkaline phosphatase levels with lupus.

7. Other causes of low alkaline phosphatase.

The below causes are not frequent with lupus. However, they may co-exist with the disease and cause significantly low levels of the alkaline phosphatase enzyme.

A. Hypophosphatasia.

It is a rare inherited disease that can present at any age (from after birth to adulthood).

It leads to very low alkaline phosphatase due to defects in the gene responsible for producing the tissue nonspecific alkaline phosphatase (TNS-ALP).

Patients with the disease have poor bone health, recurrent fractures, retarded growth, and early loss of teeth.

The disease may cause severe complications such as respiratory failure, seizures, or death.

B. End-stage osteopenia of chronic renal osteodystrophy.

Patients with advanced lupus nephritis (lupus kidney disease) may end in renal failure.

Renal failure is a disease that produces profound bone diseases (renal osteodystrophy). Advanced cases of lupus-related kidney failure may suffer from very low bone density and alkaline phosphatase.

C. Wilson’s disease.

A rare liver disease that leads to copper-related liver and brain dysfunctions. It is one of the well-recognized causes of low alkaline phosphatase.

D. Surgery (cardiac and cardiopulmonary surgery).

Patients with major cardiac or chest surgery are at higher risk of low alkaline phosphatase levels. The low levels of the enzymes appear to be related to the nutritional deficiency of minerals such as magnesium (reference).

E. Vitamin C deficiency.

Studies show that bone and serum alkaline phosphatase activity levels are reduced in patients with vitamin C deficiency (reference).