reduced alkaline phosphatase

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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


Last reviewed 01/2018