Unexpected widespread hypophosphatemia and bone disease associated with elemental formula use in infants and children

Luisa F. Gonzalez Ballesteros, Nina S. Ma, Rebecca J. Gordon, Leanne Ward, Philippe Backeljauw, Halley Wasserman, David R. Weber, Linda DiMeglio, Julie Gagne, Robert Stein, Declan Cody, Kimber Simmons, Paul Zimakas, Lisa Swartz Topor, Sungeeta Agrawal, Andrew Calabria, Peter Tebben, Ruth Faircloth, Erik Imel, Linda CaseyThomas O. Carpenter

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Objective Hypophosphatemia occurs with inadequate dietary intake, malabsorption, increased renal excretion, or shifts between intracellular and extracellular compartments. We noticed the common finding of amino-acid based elemental formula [EF] use in an unexpected number of cases of idiopathic hypophosphatemia occurring in infants and children evaluated for skeletal disease. We aimed to fully characterize the clinical profiles in these cases. Methods A retrospective chart review of children with unexplained hypophosphatemia was performed as cases accumulated from various centres in North America and Ireland. Data were analyzed to explore any relationships between feeding and biochemical or clinical features, effects of treatment, and to identify a potential mechanism. Results Fifty-one children were identified at 17 institutions with EF-associated hypophosphatemia. Most children had complex illnesses and had been solely fed Neocate® formula products for variable periods of time prior to presentation. Feeding methods varied. Hypophosphatemia was detected during evaluation of fractures or rickets. Increased alkaline phosphatase activity and appropriate renal conservation of phosphate were documented in nearly all cases. Skeletal radiographs demonstrated fractures, undermineralization, or rickets in 94% of the cases. Although the skeletal disease had often been attributed to underlying disease, most all improved with addition of supplemental phosphate or change to a different formula product. Conclusion The observed biochemical profiles indicated a deficient dietary supply or severe malabsorption of phosphate, despite adequate formula composition. When transition to an alternate formula was possible, biochemical status improved shortly after introduction to the alternate formula, with eventual improvement of skeletal abnormalities. These observations strongly implicate that bioavailability of formula phosphorus may be impaired in certain clinical settings. The widespread nature of the findings lead us to strongly recommend careful monitoring of mineral metabolism in children fed EF. Transition to alternative formula use or implementation of phosphate supplementation should be performed cautiously with as severe hypocalcemia may develop.

Original languageEnglish (US)
Pages (from-to)287-292
Number of pages6
JournalBone
Volume97
DOIs
StatePublished - Apr 1 2017

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Hypophosphatemia
Bone Diseases
Phosphates
Rickets
Feeding Methods
Hypocalcemia
North America
Ireland
Phosphorus
Biological Availability
Minerals
Alkaline Phosphatase
Kidney
Amino Acids

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Histology
  • Physiology

Cite this

Gonzalez Ballesteros, L. F., Ma, N. S., Gordon, R. J., Ward, L., Backeljauw, P., Wasserman, H., ... Carpenter, T. O. (2017). Unexpected widespread hypophosphatemia and bone disease associated with elemental formula use in infants and children. Bone, 97, 287-292. https://doi.org/10.1016/j.bone.2017.02.003

Unexpected widespread hypophosphatemia and bone disease associated with elemental formula use in infants and children. / Gonzalez Ballesteros, Luisa F.; Ma, Nina S.; Gordon, Rebecca J.; Ward, Leanne; Backeljauw, Philippe; Wasserman, Halley; Weber, David R.; DiMeglio, Linda; Gagne, Julie; Stein, Robert; Cody, Declan; Simmons, Kimber; Zimakas, Paul; Topor, Lisa Swartz; Agrawal, Sungeeta; Calabria, Andrew; Tebben, Peter; Faircloth, Ruth; Imel, Erik; Casey, Linda; Carpenter, Thomas O.

In: Bone, Vol. 97, 01.04.2017, p. 287-292.

Research output: Contribution to journalArticle

Gonzalez Ballesteros, LF, Ma, NS, Gordon, RJ, Ward, L, Backeljauw, P, Wasserman, H, Weber, DR, DiMeglio, L, Gagne, J, Stein, R, Cody, D, Simmons, K, Zimakas, P, Topor, LS, Agrawal, S, Calabria, A, Tebben, P, Faircloth, R, Imel, E, Casey, L & Carpenter, TO 2017, 'Unexpected widespread hypophosphatemia and bone disease associated with elemental formula use in infants and children', Bone, vol. 97, pp. 287-292. https://doi.org/10.1016/j.bone.2017.02.003
Gonzalez Ballesteros LF, Ma NS, Gordon RJ, Ward L, Backeljauw P, Wasserman H et al. Unexpected widespread hypophosphatemia and bone disease associated with elemental formula use in infants and children. Bone. 2017 Apr 1;97:287-292. https://doi.org/10.1016/j.bone.2017.02.003
Gonzalez Ballesteros, Luisa F. ; Ma, Nina S. ; Gordon, Rebecca J. ; Ward, Leanne ; Backeljauw, Philippe ; Wasserman, Halley ; Weber, David R. ; DiMeglio, Linda ; Gagne, Julie ; Stein, Robert ; Cody, Declan ; Simmons, Kimber ; Zimakas, Paul ; Topor, Lisa Swartz ; Agrawal, Sungeeta ; Calabria, Andrew ; Tebben, Peter ; Faircloth, Ruth ; Imel, Erik ; Casey, Linda ; Carpenter, Thomas O. / Unexpected widespread hypophosphatemia and bone disease associated with elemental formula use in infants and children. In: Bone. 2017 ; Vol. 97. pp. 287-292.
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abstract = "Objective Hypophosphatemia occurs with inadequate dietary intake, malabsorption, increased renal excretion, or shifts between intracellular and extracellular compartments. We noticed the common finding of amino-acid based elemental formula [EF] use in an unexpected number of cases of idiopathic hypophosphatemia occurring in infants and children evaluated for skeletal disease. We aimed to fully characterize the clinical profiles in these cases. Methods A retrospective chart review of children with unexplained hypophosphatemia was performed as cases accumulated from various centres in North America and Ireland. Data were analyzed to explore any relationships between feeding and biochemical or clinical features, effects of treatment, and to identify a potential mechanism. Results Fifty-one children were identified at 17 institutions with EF-associated hypophosphatemia. Most children had complex illnesses and had been solely fed Neocate{\circledR} formula products for variable periods of time prior to presentation. Feeding methods varied. Hypophosphatemia was detected during evaluation of fractures or rickets. Increased alkaline phosphatase activity and appropriate renal conservation of phosphate were documented in nearly all cases. Skeletal radiographs demonstrated fractures, undermineralization, or rickets in 94{\%} of the cases. Although the skeletal disease had often been attributed to underlying disease, most all improved with addition of supplemental phosphate or change to a different formula product. Conclusion The observed biochemical profiles indicated a deficient dietary supply or severe malabsorption of phosphate, despite adequate formula composition. When transition to an alternate formula was possible, biochemical status improved shortly after introduction to the alternate formula, with eventual improvement of skeletal abnormalities. These observations strongly implicate that bioavailability of formula phosphorus may be impaired in certain clinical settings. The widespread nature of the findings lead us to strongly recommend careful monitoring of mineral metabolism in children fed EF. Transition to alternative formula use or implementation of phosphate supplementation should be performed cautiously with as severe hypocalcemia may develop.",
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AU - Wasserman, Halley

AU - Weber, David R.

AU - DiMeglio, Linda

AU - Gagne, Julie

AU - Stein, Robert

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AU - Simmons, Kimber

AU - Zimakas, Paul

AU - Topor, Lisa Swartz

AU - Agrawal, Sungeeta

AU - Calabria, Andrew

AU - Tebben, Peter

AU - Faircloth, Ruth

AU - Imel, Erik

AU - Casey, Linda

AU - Carpenter, Thomas O.

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N2 - Objective Hypophosphatemia occurs with inadequate dietary intake, malabsorption, increased renal excretion, or shifts between intracellular and extracellular compartments. We noticed the common finding of amino-acid based elemental formula [EF] use in an unexpected number of cases of idiopathic hypophosphatemia occurring in infants and children evaluated for skeletal disease. We aimed to fully characterize the clinical profiles in these cases. Methods A retrospective chart review of children with unexplained hypophosphatemia was performed as cases accumulated from various centres in North America and Ireland. Data were analyzed to explore any relationships between feeding and biochemical or clinical features, effects of treatment, and to identify a potential mechanism. Results Fifty-one children were identified at 17 institutions with EF-associated hypophosphatemia. Most children had complex illnesses and had been solely fed Neocate® formula products for variable periods of time prior to presentation. Feeding methods varied. Hypophosphatemia was detected during evaluation of fractures or rickets. Increased alkaline phosphatase activity and appropriate renal conservation of phosphate were documented in nearly all cases. Skeletal radiographs demonstrated fractures, undermineralization, or rickets in 94% of the cases. Although the skeletal disease had often been attributed to underlying disease, most all improved with addition of supplemental phosphate or change to a different formula product. Conclusion The observed biochemical profiles indicated a deficient dietary supply or severe malabsorption of phosphate, despite adequate formula composition. When transition to an alternate formula was possible, biochemical status improved shortly after introduction to the alternate formula, with eventual improvement of skeletal abnormalities. These observations strongly implicate that bioavailability of formula phosphorus may be impaired in certain clinical settings. The widespread nature of the findings lead us to strongly recommend careful monitoring of mineral metabolism in children fed EF. Transition to alternative formula use or implementation of phosphate supplementation should be performed cautiously with as severe hypocalcemia may develop.

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