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Abstract: PO0349

FGF-23 Is Induced by Glucocorticoid Stimulation In Vivo and In Vitro: Translational Approach

Session Information

Category: Bone and Mineral Metabolism

  • 402 Bone and Mineral Metabolism: Clinical

Authors

  • Toro, Luis, Universidad de Chile Facultad de Medicina, Santiago, Chile
  • Alzamora, Rodrigo, Universidad de Chile Facultad de Medicina, Santiago, Chile
  • Barrientos, Victor, Universidad de Chile Facultad de Medicina, Santiago, Chile
  • Delucchi, Angela, Universidad de Chile Facultad de Medicina, Santiago, Chile
  • Michea, Luis, Universidad de Chile Facultad de Medicina, Santiago, Chile
Background

Previous data have suggested that glucocorticoid (GC) treatment may induce plasma fibroblast growth factor 23 (FGF23). Recently, we have reported that in prepubertal renal trasplantion children, chronic GC treatment was associated with increased plasma FGF23 levels, that was related to decreased bone growth in vivo and in vitro. Our objective was to evaluate whether GC treatment modulate FGF23 in adult patients.

Methods

Translational approach. This included an observational clinical study of patients who began GC treatment (prednisone 1 mg/kg/day), estimated glomerular filtration rate (eGFR) over 60 mL/min/1.7m2. Measurements of intact FGF23 were performed before initiation and 2 months later. Also we performed in vitro and in vivo analysis with cell cultures and experimental rat models which were treated with GC, measurements of plasma and bone FGF23 expression were performed.

Results

We recruited 10 patients who began GC treatment. We observed a significant increase in plasma intact FGF23 levels at 2 months (57% increase as compared to baseline values): baseline values: 18.9 +/- 4.2 pg/mL; 2 months: 29.7 +/- 5.2 pg/mL; p<0.001. No significant changes in renal function were detected.
Also, rats treated with prednisone had a significant increase in plasma FGF23 and bone FGF23 expression after GC treatment. Finally, pharmacological blockage of glucocorticoid receptor alpha in vitro prevented the increase of FGF23 expression in bone tissue.

Conclusion

Sustained glucocorticoid treatment is associated to increased FGF23 expression and plasma levels. This effect should be evaluated in larger groups of patients to evaluate its potential relevance.

Funding

  • Government Support - Non-U.S.