AN UNANTICIPATED OBSERVATION REGARDING FGF23 DURING ONE YEAR OF GH REPLACEMENT THERAPY
To promote linear growth, it is essential to have normal phosphate homeostasis. Growth hormone/insulin-like growth factor (GH/IGF1) axis is a major regulator of phosphate metabolism and children with growth hormone deficiency (GHD) have increased renal phosphorus reabsorption during rhGH therapy. The novel phosphaturic fibroblast growth factor 23 (FGF23) has opposing effects, but the underlying mechanisms and interplay between both systems remain unclear. Aim: The main objective of this study is to investigate the possible interactions of FGF23 with the GH/IGF1 axis in the regulation of growth, calcium-phosphorus metabolism, and bone mineral density (BMD) in GHD children during the first year of treatment. Material and methods: Prospective, observational study of 42 non-obese prepubertal GHD children of both sexes, investigating changes in plasma FGF23, markers of mineral metabolism, and IGF-1 in the first year of rhGH therapy. Results: All children grew at an accelerated pace. Total BMD and total bone mineral content significantly increased after 12 months. The increase in serum phosphate was accompanied by a significant increase in plasma cFGF23 and IGF1. We found a positive association between SDS Height with IGF1 and FGF23 levels. No impact of FGF23 concentration variations on BMD was determined. Conclusions: FGF23 rises during rhGH therapy, an unanticipated observation given the role of FGF23 as a phosphaturic factor. GHD children have increased phosphate, associated with upregulation rather than with suppression of the phosphaturic FGF23. The association of FGF23 with height and IGF1 could indicate complex interactions between both axes in promoting linear growth.
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