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Entinostat treatment causes hypophosphatemia and hypocalcemia by increasing Fgf23 in mice

Wenguang Liu1, Manyu Zhang2, Lili Wu3

  • 1School of Life Sciences, Northeast Normal University, Changchun, 130024, China.

Biochemical and Biophysical Research Communications
|November 17, 2024
PubMed

Insights

Entinostat treatment increases trabecular bone volume by reducing resorption, not by affecting bone cell formation. This cancer drug causes hypophosphatemia and hypocalcemia by increasing fibroblast growth factor 23 (FGF23).

Area of Science:

  • Oncology
  • Endocrinology
  • Bone Biology

Background:

  • Entinostat, a histone deacetylase inhibitor, is used in cancer clinical trials.
  • Entinostat treatment can lead to hypophosphatemia and hypocalcemia.
  • The impact of Entinostat on bone metabolism is not fully understood.

Purpose of the Study:

  • To investigate the effects of Entinostat on bone volume, strength, and cellular activity.
  • To elucidate the mechanisms behind Entinostat-induced mineral imbalances.
  • To assess the role of fibroblast growth factor 23 (FGF23) in Entinostat's effects.

Main Methods:

  • In vivo studies using animal models to assess bone parameters.
  • Analysis of bone cell markers (Runx2, TRAP) and serum bone turnover markers (P1NP, TRAP-5b).
  • In vitro cell proliferation assays and gene/protein expression analysis for FGF23, Runx2, and Ctsk.

Main Results:

  • Entinostat increased trabecular bone volume but not cortical bone volume or strength.
  • No significant changes in osteoblast or osteoclast markers were observed, suggesting reduced resorption.
  • Entinostat significantly increased FGF23 expression and serum levels, leading to decreased serum phosphate and calcium.

Conclusions:

  • Entinostat increases trabecular bone volume by potentially attenuating bone resorption, independent of osteoblastogenesis or osteoclastogenesis.
  • Entinostat induces hypophosphatemia and hypocalcemia through the upregulation of FGF23.
  • These findings highlight potential concerns regarding Entinostat's effects on bone metabolism and mineral homeostasis.
Keywords:
BoneEntinostatFgf23HypocalcemiaHypophosphatemia

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