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
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