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Case Reports
. 2017 Apr;97:287-292.
doi: 10.1016/j.bone.2017.02.003. Epub 2017 Feb 4.

Unexpected Widespread Hypophosphatemia and Bone Disease Associated With Elemental Formula Use in Infants and Children

Free PMC article
Case Reports

Unexpected Widespread Hypophosphatemia and Bone Disease Associated With Elemental Formula Use in Infants and Children

Luisa F Gonzalez Ballesteros et al. Bone. .
Free PMC article


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.

Conflict of interest statement


Thomas O. Carpenter and Linda Casey have performed consulting services for Nutricia, North America. The other authors have indicated they have no financial relationships relevant to this article to disclose.

Conflict of interest

Ruth Faircloth, MD: The views expressed are those of the authors and do not reflect the official policy or position of the US Army, Department of Defense nor the US Government. The other authors have no potential conflicts of interest to disclose.


Fig. 1
Fig. 1
Changes in serum calcium (blue), phosphorus (pink) and alkaline phosphatase (purple) in an 8 month-old girl fed Neocate® since age 2 months due to milk protein allergy, presenting with a tibial fracture. After the formula was changed to Elecare®, serum phosphorus and alkaline phosphatase levels corrected. Supplemental phosphate was not administered.
Fig. 2
Fig. 2
Radiographs showing severe rickets at presentation (left) and improvement 5 weeks after formula change (right).

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