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Osteoporos Int. 2014 Feb;25(2):519-23. doi: 10.1007/s00198-013-2447-x. Epub 2013 Aug 3.

Acute hypophosphatasemia.

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Center for Bone Disease, Marshfield Clinic, 1000 North Oak Avenue, Marshfield, WI, 54449, USA,


The temporal evolution of a low serum alkaline phosphatase value may relate to its cause. Precipitous lowering of serum alkaline phosphatase below the lower range of normal is uncommon and may indicate severe physiologic stress and increased short-term mortality.


The differential diagnosis of a low serum alkaline phosphatase (ALP) value (hypophosphatasemia) is wide ranging, anecdotal, and unfamiliar. The temporal evolution of hypophosphatasemia may relate to its cause. The purpose of this study is to report conditions and circumstances associated with precipitous lowering of serum ALP below the lower range of normal.


Marshfield Clinic IRB approved use of their electronic medical record to search for subjects with at least two serum ALP values ≤ 40 U/L (normal 40-125 U/L). When the temporal evolution of the qualifying ALP values indicated a precipitous lowering from usually normal serum ALP values, the subject was deemed to have acute hypophosphatasemia. Thirty years of laboratory data and 10 years of clinical narrative were analyzed. Associated diagnoses, clinical circumstances, and short-term mortality were recorded.


A total of 458,767 subjects had 2,584,051 serum ALP values, and 5,190 (1.1 %) subjects had at least two serum values ≤ 40 U/L. A detailed review of 1,276 subjects selected on the basis of their lowest ALP value and age identified 190 subjects with acute hypophosphatasemia. Acute hypophosphatasemia was recorded during periods of major trauma/surgery, multisystem failure, acute anemia, blood product transfusions (often massive), apheresis, hypomagnesemia, and acute caloric restriction. Twenty-eight subjects (15 %) died within 35 days of their nadir serum ALP.


Acute hypophosphatasemia is associated with profound illness or physiologic stress and followed by increased short-term mortality. The temporal evolution of hypophosphatasemia may relate to its cause.

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