title: Effect of Cinacalcet and Vitamin D Analogs on Fibroblast Growth Factor-23 during the Treatment of Secondary Hyperparathyroidism.
abstract: OBJECTIVE
  Cinacalcet and vitamin D are often combined to treat secondary hyperparathyroidism (SHPT) in patients on dialysis. Independent effects on fibroblast growth factor-23 (FGF-23) concentrations in patients on hemodialysis administered cinacalcet or vitamin D analogs as monotherapies during treatment of SHPT are evaluated.
  
  
  METHODS
  A multicenter, randomized, open-label study to compare the efficacy of cinacalcet versus traditional vitamin D therapy for management of secondary hyperparathyroidism among subjects undergoing hemodialysis (PARADIGM) was a prospective, phase 4, multicenter, randomized, open-label study conducted globally. Participants (n=312) were randomized 1:1 to cinacalcet (n=155) or vitamin D analog (n=157) for 52 weeks. Levels of FGF-23 were measured at baseline and weeks 20 and 52. The absolute and percentage changes from baseline in plasma FGF-23, parathyroid hormone (PTH), calcium (Ca), phosphorus (P), and calcium-phosphorus product (Ca×P) were assessed. Correlations and logistic regression were used to explore relationships between changes in FGF-23 and changes in PTH, Ca, P, and Ca×P from baseline to week 52 by treatment arm.
  
  
  RESULTS
  Median (quartiles 1, 3) decrease in FGF-23 concentrations was observed in the cinacalcet arm (-40%; -63%, 16%) compared with median increase in the vitamin D analog arm (47%; 0%, 132%) at week 52 (P<0.001). Changes in FGF-23 in both arms were unrelated to changes in PTH (cinacalcet: r=0.17, P=0.11; vitamin D analog: r=-0.04, P=0.70). Changes in FGF-23 in the vitamin D analog but not the cinacalcet arm were correlated with changes in Ca (cinacalcet: r=0.11, P=0.30; vitamin D analog: r=0.32, P<0.01) and P (cinacalcet: r=0.19, P=0.07; vitamin D analog: r=0.49, P<0.001). Changes in FGF-23 were correlated with changes in Ca×P in both arms (cinacalcet: r=0.26, P=0.01; vitamin D analog: r=0.57, P<0.001). Independent of treatment arm, participants with reductions in P or Ca×P were significantly more likely to show reductions in FGF-23.
  
  
  CONCLUSIONS
  During treatment of SHPT, cinacalcet use was associated with a decrease in FGF-23 concentrations, whereas vitamin D analogs were associated with an increase. The divergent effects of these treatments on FGF-23 seem to be independent of modification of PTH. It is possible that effects of cinacalcet and vitamin D analogs on FGF-23 may be mediated indirectly by other effects on bone and mineral metabolism.
authors: Division of Nephrology and Hypertension, NorthShore University HealthSystem, Evanston, Illinois; ssprague@northshore.org.
authors: Stuart M
authors: SM
authors: Sprague
authors: Division of Nephrology, Hennepin County Medical Center, Minneapolis, Minnesota;
authors: James B
authors: JB
authors: Wetmore
authors: Fresenius Medical Care, St. Petersburg, Russia;
authors: Konstantin
authors: K
authors: Gurevich
authors: Division of Nephrology, Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada;
authors: Gerald
authors: G
authors: Da Roza
authors: Columbia Nephrology Associates, Columbia, South Carolina; and.
authors: John
authors: J
authors: Buerkert
authors: Clinical Research, Amgen Inc., Thousand Oaks, California.
authors: Maureen
authors: M
authors: Reiner
authors: Clinical Research, Amgen Inc., Thousand Oaks, California.
authors: William
authors: W
authors: Goodman
authors: Clinical Research, Amgen Inc., Thousand Oaks, California.
authors: Kerry
authors: K
authors: Cooper
mesh_terms: D000368:Aged; D001315:Australia; D015415:Biomarkers / Q000097:blood; D057966:Calcimimetic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002118:Calcium / Q000097:blood; D002170:Canada; D016009:Chi-Square Distribution; D000069449:Cinacalcet / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000097:blood*; D006801:Humans; D006962:Hyperparathyroidism, Secondary / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D007676:Kidney Failure, Chronic / Q000097:blood / Q000150:complications / Q000175:diagnosis / Q000628:therapy*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D010281:Parathyroid Hormone / Q000097:blood; D010758:Phosphorus / Q000097:blood; D011446:Prospective Studies; D006435:Renal Dialysis / Q000009:adverse effects; D012307:Risk Factors; D012426:Russia; D013997:Time Factors; D016896:Treatment Outcome; D014481:United States; D014807:Vitamin D / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use*
chemical_list: D015415:Biomarkers; D057966:Calcimimetic Agents; C000717427:FGF23 protein, human; C470125:PTH protein, human; D010281:Parathyroid Hormone; D014807:Vitamin D; D010758:Phosphorus; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23; D002118:Calcium; D000069449:Cinacalcet
keywords: ESRD; clinical nephrology; dialysis; hyperparathyroidism