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Published in: Osteoporosis International 2/2014

01-02-2014 | Original Article

Acute hypophosphatasemia

Authors: F. E. McKiernan, L. K. Shrestha, R. L. Berg, J. Fuehrer

Published in: Osteoporosis International | Issue 2/2014

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Abstract

Summary

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.

Introduction

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.

Methods

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.

Results

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.

Conclusion

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.
Literature
1.
go back to reference Millán JL (2006) Mammalian alkaline phosphatases: from biology to applications in medicine and biotechnology. Wiley-VCH, Weinheim, pp 1–322CrossRef Millán JL (2006) Mammalian alkaline phosphatases: from biology to applications in medicine and biotechnology. Wiley-VCH, Weinheim, pp 1–322CrossRef
2.
go back to reference McComb RB, Bowers GN, Posen S (eds) (1979) Clinical utilization of alkaline phosphatase measurements. In: Alkaline phosphatase, Plenum Press, New York, pp 525–786 McComb RB, Bowers GN, Posen S (eds) (1979) Clinical utilization of alkaline phosphatase measurements. In: Alkaline phosphatase, Plenum Press, New York, pp 525–786
3.
go back to reference Whyte MP (2012) Hypophosphatasia. In: Glorieux FH, Pettifor JM, Juppner H (eds) Pediatric bone biology and diseases, 2nd edn. Academic Press, New York, pp 771–794CrossRef Whyte MP (2012) Hypophosphatasia. In: Glorieux FH, Pettifor JM, Juppner H (eds) Pediatric bone biology and diseases, 2nd edn. Academic Press, New York, pp 771–794CrossRef
4.
go back to reference Wilke RA, Berg RL, Peissig P, Kitchner T, Sijercic B, McCarty CA, McCarty DJ (2007) Use of an electronic medical record for the identification of research subjects with diabetes mellitus. Clin Med Res 5:1–7PubMedCentralPubMedCrossRef Wilke RA, Berg RL, Peissig P, Kitchner T, Sijercic B, McCarty CA, McCarty DJ (2007) Use of an electronic medical record for the identification of research subjects with diabetes mellitus. Clin Med Res 5:1–7PubMedCentralPubMedCrossRef
6.
go back to reference McKiernan F, Berg J, Linneman J (2011) Should low BMD Z-scores prompt evaluation for secondary causes of osteoporosis? Osteoporos Int 22:1069–1077PubMedCrossRef McKiernan F, Berg J, Linneman J (2011) Should low BMD Z-scores prompt evaluation for secondary causes of osteoporosis? Osteoporos Int 22:1069–1077PubMedCrossRef
8.
go back to reference Lum G (1995) Significance of low alkaline phosphatase activity in a predominantly adult male population. Clin Chem 41:515–518PubMed Lum G (1995) Significance of low alkaline phosphatase activity in a predominantly adult male population. Clin Chem 41:515–518PubMed
9.
go back to reference Macfarlane JD, Souverijn JHM, Breedveld FC (1992) Clinical significance of a low serum alkaline phosphatase. Neth J Med 40:9–14PubMed Macfarlane JD, Souverijn JHM, Breedveld FC (1992) Clinical significance of a low serum alkaline phosphatase. Neth J Med 40:9–14PubMed
10.
go back to reference Lum G, Marquardt C, Khuri SF (1989) Hypomagnesemia and low alkaline phosphatase activity in patients after cardiac surgery. Clin Chem 35:664–666PubMed Lum G, Marquardt C, Khuri SF (1989) Hypomagnesemia and low alkaline phosphatase activity in patients after cardiac surgery. Clin Chem 35:664–666PubMed
12.
go back to reference Whyte MP (2010) Physiologic role of alkaline phosphatase explored in hypophosphatasia. Ann NY Acad Sci 1192:190–200PubMedCrossRef Whyte MP (2010) Physiologic role of alkaline phosphatase explored in hypophosphatasia. Ann NY Acad Sci 1192:190–200PubMedCrossRef
13.
go back to reference Oosthuizen NM (2011) Undetectable serum alkaline phosphatase activity in a patient with fulminant hepatic failure and hemolytic anemia. Clin Chem 57:382–387PubMedCrossRef Oosthuizen NM (2011) Undetectable serum alkaline phosphatase activity in a patient with fulminant hepatic failure and hemolytic anemia. Clin Chem 57:382–387PubMedCrossRef
14.
go back to reference Greenspan SL, Emkey RD, Bone HG, Weiss SR, Bell NH, Downs RW, McKeever C, Miller SS, Davidson M, Bolognese MA, Mulloy AL, Heyden N, WU M, Kaur A, Lombardi A (2002) Significant differential effects of alendronate, estrogen, or combination therapy on the rate of bone loss after discontinuation of treatment of postmenopausal osteoporosis. Ann Intern Med 137:875–883PubMedCrossRef Greenspan SL, Emkey RD, Bone HG, Weiss SR, Bell NH, Downs RW, McKeever C, Miller SS, Davidson M, Bolognese MA, Mulloy AL, Heyden N, WU M, Kaur A, Lombardi A (2002) Significant differential effects of alendronate, estrogen, or combination therapy on the rate of bone loss after discontinuation of treatment of postmenopausal osteoporosis. Ann Intern Med 137:875–883PubMedCrossRef
15.
go back to reference Dufour DR (2011) Undetectable serum alkaline phosphatase activity in a patient with fulminant hepatic failure and hemolytic anemia [comment]. Clin Chem 57:385–386PubMedCrossRef Dufour DR (2011) Undetectable serum alkaline phosphatase activity in a patient with fulminant hepatic failure and hemolytic anemia [comment]. Clin Chem 57:385–386PubMedCrossRef
16.
go back to reference Coburn SP, Mahuren D, Jain M, Zubovik Y, Wortsman J (1998) Alkaline phosphatase (EC3.1.3.1) in serum is inhibited by physiologic concentrations of inorganic phosphate. J Clin Endocrinol Metab 83:3951–3957PubMed Coburn SP, Mahuren D, Jain M, Zubovik Y, Wortsman J (1998) Alkaline phosphatase (EC3.1.3.1) in serum is inhibited by physiologic concentrations of inorganic phosphate. J Clin Endocrinol Metab 83:3951–3957PubMed
Metadata
Title
Acute hypophosphatasemia
Authors
F. E. McKiernan
L. K. Shrestha
R. L. Berg
J. Fuehrer
Publication date
01-02-2014
Publisher
Springer London
Published in
Osteoporosis International / Issue 2/2014
Print ISSN: 0937-941X
Electronic ISSN: 1433-2965
DOI
https://doi.org/10.1007/s00198-013-2447-x

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