reduced alkaline phosphatase

Last reviewed 10/2023

A study examined causes for low serum alkaline phosphatase (ALP) activity in a large Veterans Medical Center were reviewed. Of 69,864 ALP determinations made over a 4-year period, 130 were low (<30 U/L, 0.19%), representing 88 individual patients (1):

• of these, 83 (primarily men, 96%) patients' charts were reviewed and classified into two groups, those with and those without conditions previously reported to be associated with decreased serum ALP activity:
  • 47% had conditions associated with low ALP activity, the most frequent being cardiac surgery and cardiopulmonary bypass (26.5%), malnutrition (12.0%), magnesium deficiency (4.8%), hypothyroidism (2.4%), and severe anaemia (1.2%)
    • decreases in both ALP and magnesium observed in the postcardiac surgery patients appear to be a consequence of the cardiac surgery and cardiopulmonary bypass, and could not be attributed to haemodilution alone
      • magnesium ion is an activator of ALP activity, but the addition of magnesium to serum samples from postoperative cardiac surgery patients with low ALP activity failed to restore ALP activity; this suggests that factors other than magnesium necessary for ALP activity were removed by the cardiopulmonary pump
  • 53% of patients did not have clinical conditions previously associated with low ALP activity
  • no case of clinically apparent hypophosphatasia, for which low ALP activity is the defining characteristic, was found in this population of veterans

There is a vast list of stated possible causes (1,2) for a low alkaline phosphatase (ALP) level - less than 30IU:

• zinc deficiency
• magnesium deficiency
• hypophosphatasia
  • an inborn error of metabolism, is characterized clinically by defective bone mineralization, resulting in excessive unmineralized bone matrix, and biochemically by deficient activity of the tissue-nonspecific isoenzyme of ALP in tissues and in serum, increased urinary excretion of phosphoethanolamine and inorganic pyrophosphate, increased plasma pyridoxal 5'- phosphate, decreased total serum ALP activity, and radiological, histological, and clinical features of rickets
• cardiac surgery and cardiopulmonary bypass
• artifacts associated with collection of blood in EDTA or oxalate anticoagulant
• hypothyroidism
  • associated with low serum ALP activity, which returns to normal after therapy with thyroid hormones
• severe anaemia
• pernicious anaemia
  • in pernicious anaemia, osteoblast activity is dependent on cobalamin, and bone metabolism is affected by deficiency of cobalamin
    • cobalamin-deficient patients have significantly lower concentrations of serum ALP (skeletal ALP) and osteocalcin than do unaffected control patients
• protein/calorie deficiency
• oestrogen replacement therapy in postmenopausal women
  • oestrogen replacement therapy in postmenopausal women with osteoporosis is associated with low ALP concentrations, an effect attributed to inhibition of bone resorption by oestrogen
• end-stage osteopaenia of chronic renal osteodystrophy
• Wilson's disease
• achondroplasia and hypothyroidism in children
  • in children, decreased or low ALP activity may signal disturbed skeletal growth , the cessation of bone growth, or clinical conditions such as achondroplasia
• vitamin C deficiency
• other conditions that have suggested as possible causes of a low ALP include:
  • milk-alkali syndrome, excess ingestion of vitamin D, coeliac disease, hypoparathyroidism, intake of radioactive heavy metal, drugs such as clofibrate, recent massive blood transfusions, or posthepatic resection and transplantation

Reference:

• 1) Lum G. Significance of low serum alkaline phosphatase activity in a predominantly adult male population.Clin Chem. 1995 Apr;41(4):515-8.
• 2) Shaver WA et al. Low serum alkaline phosphatase activity in Wilson's disease.Hepatology. 1986 Sep-Oct;6(5):859-63