Long-Term Follow-up of Hypophosphatemic Bone Disease Associated With Elemental Formula Use: Sustained Correction of Bone Disease After Formula Change or Phosphate Supplementation

Abstract

In this article, we describe the long-term outcomes of children who were previously reported to have developed hypophosphatemic bone disease in association with elemental formula use. An extended chart review allowed for an updated report of 34 children with regard to severity/duration of bone disease, extent of recovery, and time to correction using radiology reports and biochemical data. After implementation of formula change and/or phosphate supplementation, we found that serum phosphorus concentration increased and serum alkaline phosphatase activity decreased in all patients, normalizing by 6.6 ± 4.0 (mean ± SD) months following diagnosis. The decrease in serum alkaline phosphatase from diagnosis to the time of correction was moderately correlated with the concurrent increase in serum phosphorus ( R = 0.48, P < .05). Age at diagnosis significantly correlated with time to resolution ( R = 0.51, P = .01). This study supports the earlier report that bone disease associated with hypophosphatemia during elemental formula use responds to formula change and/or phosphate supplementation.

Nutritional Management With a Casein-Based Extensively Hydrolysed Formula in Infants With Clinical Manifestations of Non-IgE-Mediated CMPA Enteropathies and Constipation

“…However, AAF has been reported to lack the capability of building up tolerance and imposes high economic burden on families and healthcare systems (5,19,20). In addition, as the average duration of formula use in this case studies was longer than 6 months, prolonged use of AAF could increase the risk of hypophosphatemia and rickets as reported earlier (20)(21)(22)(23)(24). Therefore, clinicians should limit its use for extremely severe cases and when eHF is not tolerated, which is supported by this study findings (9,25,26).…”

Strategies and Future Opportunities for the Prevention, Diagnosis, and Management of Cow Milk Allergy

“…As tolerance development is thought to be an antigen-driven process, the use of AAF is unlikely to promote tolerance development (113) although a recent study showed that supplementing AAF with synbiotics improved the gut microbiota in non-IgE mediated allergic infants (114). The use of AAF for more than 6 months in children was recently reported to have the potential adverse effect of causing hypophosphatemic bone disease especially among those with complex GI conditions (115)(116)(117)(118)(119). These studies also reported restoration of calcium and phosphorus homeostasis following a formula change to eHF.…”

Genetic causes of neonatal and infantile hypercalcaemia

“…In particular, hypophosphatemia has been associated with parenteral nutrition with a high amino acid content, and formulas with equimolar (0.75:1 to 1:1) Ca 2+ :PO 4 ratios, along with careful monitoring of electrolytes including phosphorus have been r e c o m m e n d e d t o p r e v e n t h y p e r c a l c a e m i a a n d hypophosphatemia [33,34]. Hypophosphatemia has been described in some infants given correctly prepared formulas, and it has been suggested that bioavailability of phosphorus may be suboptimal in some infants in the context of gastrointestinal disease or tube feeding [35]. Formula change and/or phosphate supplementation improved hypophosphatemia in these infants [35].…”

“…Hypophosphatemia has been described in some infants given correctly prepared formulas, and it has been suggested that bioavailability of phosphorus may be suboptimal in some infants in the context of gastrointestinal disease or tube feeding [ 35 ]. Formula change and/or phosphate supplementation improved hypophosphatemia in these infants [ 35 ].…”