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

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.

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

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.

Two Case Reports of FGF23-Induced Hypophosphatemia in Childhood Biliary Atresia.

Cholestatic liver disease has long been associated with childhood rickets, secondary to impaired absorption of fat-soluble vitamin D. Elevated serum levels of fibroblast growth factor 23 (FGF23), secondary to genetic defects or tumor-induced osteomalacia, causes hypophosphatemic rickets in childhood. We present 2 infants with end-stage liver disease due to biliary atresia (BA) who developed hypophosphatemia with renal phosphate wasting. Serum FGF23 levels were elevated more than 8 times the upper limit of normal, and the older infant showed radiographic evidence of rickets. Both infants required large supplements of phosphate in addition to calcitriol. Following liver transplantation, FGF23 normalized in both patients and phosphate and calcitriol supplementation were discontinued. Immunohistochemistry revealed ectopic overexpression of FGF23 by hepatocytes in the BA liver. These observations highlight a unique cause of hypophosphatemic rickets in childhood and suggest the need for further investigation into the relationship between BA and other cholestatic disorders, and bone metabolism.

Growth, bone mineral accretion, and adrenal function in glucocorticoid-treated infants with hemangiomas-- a retrospective study.

Hemangiomas, common proliferative vascular tumors, can grow rapidly in the first months of life. Although therapy with high-dose oral glucocorticoids is standard for lesions that threaten vital functions or are disfiguring, little is known about the endocrine consequences of this treatment. Using retrospective data, we examined growth velocity, changes in bone mineral density, and adrenal function in infants with hemangiomas treated with systemic glucocorticoids. Treatment consisted of oral prednisolone 2 to 4 mg/kg/day or dexamethasone 1 mg/kg/day. Mean growth velocity Z score on glucocorticoid therapy was -1.41 standard deviations in 13 patients. In four infants with adequate follow-up, growth velocity increased to +1.90 standard deviations after glucocorticoid treatment (Delta growth velocity +3.31 standard deviations). Mean lumbar spine bone mineral density Z score was -2.46 standard deviations before glucocorticoid treatment and -1.08 standard deviations at the end of treatment in six infants. Adrenal function after glucocorticoid therapy was assessed by low-dose adrenocorticotropic hormone stimulation test in 10 infants. Eight had a normal cortisol response, and one had a borderline response. One infant, who had been treated with dexamethasone, had an abnormal test result. In conclusion, systemic glucocorticoid treatment in infants with hemangiomas slowed linear growth, but "catch-up" growth was observed after treatment ceased. Glucocorticoids did not affect bone mineralization adversely. Only 1 of 10 glucocorticoid-treated infants had clear evidence of adrenal insufficiency after therapy was stopped.