Cinacalcet lowers FGF-23 level together with bone metabolism in hemodialyzed patients with secondary hyperparathyroidism

Int Urol Nephrol. 2012 Oct;44(5):1479-86. doi: 10.1007/s11255-011-0050-7. Epub 2011 Aug 27.

Abstract

Purpose: Secondary hyperparathyroidism (sHPT) is associated with elevated levels of FGF-23, which in turn are connected to adverse outcomes in ESRD patients. The relationship between FGF-23 and bone metabolism in patients with sHPT treated with cinacalcet has not been studied.

Methods: Thirty-four stable chronically hemodialyzed patients with sHPT were prospectively followed during the treatment with cinacalcet without any changes in concurrent vitamin D or phosphate binder dose. Blood samples were collected at the start and after 6 months of study. Levels of osteocalcin (OC), cross-linked C-telopeptide of type I collagen (CTX), and FGF-23 were measured.

Results: Eighteen patients finished the study. Levels of calcium, phosphate, and iPTH decreased during 6 months of treatment with cinacalcet. Serum level of FGF-23 decreased significantly (log FGF-23 from 7.58 ± 1.7 to 6.61 ± 1.7 pg/ml) (P < 0.001). Cinacalcet lowered the concentration of CTX from 3.1 ± 0.6 ng/ml to 2.6 ± 0.9 ng/ml (P < 0.05) and OC from 91.8 (41.5-558.6) to 70.3 (11.3-419.7) ng/ml (P < 0.05). The magnitude of change in FGF-23 concentration before and after treatment correlated significantly with suppression of osteoblasts' function assessed by ΔOC (r = 0.5, P < 0.05) but not with changes in bone resorption marker ΔCTX.

Conclusions: Cinacalcet treatment of sHPT results in reduction of FGF-23 levels, probably due to the suppression of osteoblasts function.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Bone and Bones / drug effects*
  • Bone and Bones / metabolism*
  • Calcimimetic Agents / pharmacology*
  • Calcimimetic Agents / therapeutic use
  • Cinacalcet
  • Collagen Type I / blood
  • Female
  • Fibroblast Growth Factor-23
  • Fibroblast Growth Factors / blood*
  • Humans
  • Hyperparathyroidism, Secondary / blood*
  • Hyperparathyroidism, Secondary / drug therapy
  • Male
  • Middle Aged
  • Naphthalenes / pharmacology*
  • Naphthalenes / therapeutic use
  • Osteoblasts / drug effects
  • Osteocalcin / blood
  • Parathyroid Hormone / blood
  • Peptides / blood
  • Renal Dialysis / adverse effects
  • Renal Insufficiency, Chronic / therapy

Substances

  • Calcimimetic Agents
  • Collagen Type I
  • FGF23 protein, human
  • Naphthalenes
  • Parathyroid Hormone
  • Peptides
  • collagen type I trimeric cross-linked peptide
  • Osteocalcin
  • Fibroblast Growth Factors
  • Fibroblast Growth Factor-23
  • Cinacalcet